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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Introdu&#231;&#227;o</span><p id="par0005" class="elsevierStylePara elsevierViewall">Estima&#8208;se que em torno de 16&#37; de todos os casos de c&#226;ncer no mundo est&#227;o relacionados a agentes infecciosos&#44; e aproximadamente 10&#37; a 12&#37; desses casos est&#227;o associados aos v&#237;rus&#46;<a class="elsevierStyleCrossRefs" href="#bib0375"><span class="elsevierStyleSup">1&#8211;3</span></a> Os oncov&#237;rus humanos&#44; v&#237;rus identificados como agentes etiol&#243;gicos de alguns tipos de c&#226;ncer e com capacidade oncog&#234;nica inequ&#237;voca&#44; amplamente aceitos pela comunidade cient&#237;fica atualmente&#44; s&#227;o&#58; os papilomav&#237;rus humanos &#40;HPV&#41;&#59; v&#237;rus da hepatite B&#59; v&#237;rus da hepatite C&#59; v&#237;rus Epstein&#8208;Barr&#59; herpes&#8208;v&#237;rus humano 8&#59; v&#237;rus linfotr&#243;pico de c&#233;lulas T humanas &#40;HTLV&#41; e poliomav&#237;rus de c&#233;lulas de Merkel &#40;MCPyV&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0390"><span class="elsevierStyleSup">4&#44;5</span></a> Essa conclus&#227;o &#233; feita com base no conhecimento acumulado de um grande n&#250;mero de estudos experimentais&#44; cl&#237;nicos e epidemiol&#243;gicos das &#250;ltimos cinco d&#233;cadas&#46;<a class="elsevierStyleCrossRefs" href="#bib0375"><span class="elsevierStyleSup">1&#8211;5</span></a> Apesar de muitas viroses animais e humanas poderem transformar c&#233;lulas normais em oncog&#234;nicas&#44; ainda h&#225; poucas viroses consistentemente associadas &#224;s neoplasias nos humanos&#46; Dentre os v&#237;rus que causam infec&#231;&#227;o persistente e que t&#234;m comprovado potencial oncog&#234;nico&#44; destacam&#8208;se os poliomav&#237;rus &#40;PyV&#41;&#44; que s&#227;o&#44; com frequ&#234;ncia&#44; encontrados em les&#245;es neopl&#225;sicas&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">&#201; not&#225;vel&#44; tamb&#233;m&#44; que em virtude da onipresen&#231;a e persist&#234;ncia desses v&#237;rus&#44; sua associa&#231;&#227;o causal com essas neoplasias e outras les&#245;es n&#227;o neopl&#225;sicas variadas &#233; de dif&#237;cil interpreta&#231;&#227;o&#46; Postula&#8208;se que a reativa&#231;&#227;o e cronifica&#231;&#227;o dessas infec&#231;&#245;es possam estar relacionadas ao processo de maligniza&#231;&#227;o em decorr&#234;ncia da inj&#250;ria tecidual cr&#244;nica&#46; Al&#233;m disso&#44; tem sido relatada a presen&#231;a concomitante desses agentes virais em alguns tumores&#44; indicando poss&#237;vel papel coestimulat&#243;rio do processo infeccioso&#46;<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">1</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">A oncog&#234;nese &#233; via multifatorial&#44; e sistemas virais suportam a no&#231;&#227;o de que o desenvolvimento do tumor ocorre pelo ac&#250;mulo de eventos m&#250;ltiplos&#44; enquanto a presen&#231;a do DNA viral nas c&#233;lulas tumorais n&#227;o &#233;&#44; necessariamente&#44; um fator causal&#46; A transforma&#231;&#227;o celular causada pela infec&#231;&#227;o viral pode conduzir &#224; ativa&#231;&#227;o de oncogenes ou &#224; inativa&#231;&#227;o de genes supressores de tumor&#44; tornando&#8208;se mecanismos importantes na oncog&#234;nese viral&#46;<a class="elsevierStyleCrossRefs" href="#bib0400"><span class="elsevierStyleSup">6&#44;7</span></a> A produ&#231;&#227;o de prote&#237;nas oncog&#234;nicas consiste no principal mecanismo oncog&#234;nico de alguns retrov&#237;rus&#44; enquanto a inativa&#231;&#227;o de prote&#237;nas supressoras de tumor ocorre em alguns v&#237;rus de DNA como os PyV&#46; Para esses&#44; a inibi&#231;&#227;o e degrada&#231;&#227;o das prote&#237;nas regulat&#243;rias como a prote&#237;na p53 e a prote&#237;na do retinoblastoma consiste em sua principal estrat&#233;gia&#46;<a class="elsevierStyleCrossRefs" href="#bib0400"><span class="elsevierStyleSup">6&#44;7</span></a> Al&#233;m disso&#44; a inflama&#231;&#227;o cr&#244;nica&#44; muitas vezes causada por outros agentes infecciosos&#44; pode levar ao aumento do risco de c&#226;ncer&#44; como nos casos de c&#226;ncer de c&#243;lon na colite ulcerativa&#46; A compet&#234;ncia do sistema imune tamb&#233;m &#233; fundamental para o controle do processo infeccioso e oncog&#234;nico&#59; a imunossupress&#227;o &#233; um dos principais fatores de risco de progress&#227;o para neoplasias&#46;<a class="elsevierStyleCrossRefs" href="#bib0400"><span class="elsevierStyleSup">6&#44;7</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Desde a descoberta do MCPyV&#44; em 2008&#44;<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">8</span></a> considerado o primeiro PyV humano inequivocamente relacionado &#224; uma neoplasia em humanos&#44; o carcinoma de c&#233;lulas de Merkel &#40;CCM&#41;&#44; uma neoplasia rara&#44; de origem possivelmente neuroend&#243;crina e de curso agressivo&#44; a detec&#231;&#227;o do seu genoma viral come&#231;ou a ser investigada n&#227;o apenas em casos de CCM&#44; mas tamb&#233;m em diversas outras neoplasias cut&#226;neas&#44; denominados de c&#226;ncer de pele n&#227;o melanoma &#40;CPNM&#41; ou carcinoma de queratin&#243;citos &#40;CQ&#41;&#44; como o carcinoma basocelular &#40;CBC&#41; e o carcinoma cut&#226;neo de c&#233;lulas escamosas &#40;CEC&#41;&#44; o que despertou grande interesse de diversos pesquisadores&#46;<a class="elsevierStyleCrossRefs" href="#bib0415"><span class="elsevierStyleSup">9&#8211;13</span></a></p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Hist&#243;ria do poliomav&#237;rus e do poliomav&#237;rus de c&#233;lulas de Merkel</span><p id="par0025" class="elsevierStylePara elsevierViewall">O primeiro PyV foi isolado em 1953 por Ludwik Gross&#44; e recebeu esse nome por ser agente causal de m&#250;ltiplos tumores em roedores &#40;do grego <span class="elsevierStyleItalic">poli</span>&#58; m&#250;ltiplos&#59; <span class="elsevierStyleItalic">oma</span>&#59; tumores&#41;&#46; Desde ent&#227;o&#44; foram descobertas novas esp&#233;cies de PyV&#44; que infectam mam&#237;feros&#44; p&#225;ssaros e peixes&#46;<a class="elsevierStyleCrossRef" href="#bib0440"><span class="elsevierStyleSup">14</span></a> S&#227;o v&#237;rus n&#227;o envelopados&#44; icosa&#233;dricos&#44; com tamanho aproximado de 45<span class="elsevierStyleHsp" style=""></span>nm&#44; com DNA de dupla fita&#46; Seu genoma viral &#233; dividido em tr&#234;s regi&#245;es principais&#58; regi&#227;o controle n&#227;o codificante &#40;RCNC ou NCCR&#44; <span class="elsevierStyleItalic">non coding control region</span>&#41;&#44; respons&#225;vel pelos elementos para regula&#231;&#227;o da replica&#231;&#227;o e transcri&#231;&#227;o viral&#59; regi&#227;o de codifica&#231;&#227;o inicial &#40;<span class="elsevierStyleItalic">early region</span>&#41;&#44; que codifica o ant&#237;geno&#8208;T maior &#40;L<span class="elsevierStyleItalic">arge T antigen</span> ou LT&#8208;Ag&#41; e o ant&#237;geno&#8208;T menor &#40;<span class="elsevierStyleItalic">small T antigen</span> ou sT&#8208;Ag&#41;&#59; e regi&#227;o de codifica&#231;&#227;o tardia &#40;<span class="elsevierStyleItalic">late region</span>&#41;&#44; que codifica as prote&#237;nas estruturais expressas ap&#243;s o in&#237;cio da replica&#231;&#227;o do DNA&#58; prote&#237;na do caps&#237;dio viral 1 ou VP1&#44; prote&#237;na do caps&#237;dio Viral 2 ou VP2 e prote&#237;na do caps&#237;dio viral 3 ou VP3&#44; que formam o caps&#237;dio viral &#40;<a class="elsevierStyleCrossRef" href="#fig0005">fig&#46; 1</a>&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0445"><span class="elsevierStyleSup">15</span></a></p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">O ritmo em que os PyV est&#227;o sendo descobertos aumentou enormemente nos &#250;ltimos 10 anos&#44; havendo constantes atualiza&#231;&#245;es e revis&#245;es na taxonomia realizadas pelo Comit&#234; Internacional de Taxonomia de V&#237;rus &#40;ICTV&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0440"><span class="elsevierStyleSup">14</span></a> Atualmente&#44; divide&#8208;se a fam&#237;lia Polyomaviridae em seis g&#234;neros e 117 esp&#233;cies com base nas rela&#231;&#245;es filogen&#233;ticas da sequ&#234;ncia de amino&#225;cido do LT&#8208;Ag&#58; <span class="elsevierStyleItalic">Alphapolyomavirus</span>&#44; <span class="elsevierStyleItalic">Betapolyomavirus</span>&#44; <span class="elsevierStyleItalic">Gammapolyomavirus</span>&#44; <span class="elsevierStyleItalic">Deltapolyomavirus</span>&#44; <span class="elsevierStyleItalic">Epsilonpolyomavirus</span> e <span class="elsevierStyleItalic">Zetapolyomavirus</span>&#44; acrescido de um grupamento de esp&#233;cies ainda sem g&#234;nero definido&#46;<a class="elsevierStyleCrossRef" href="#bib0450"><span class="elsevierStyleSup">16</span></a> O g&#234;nero <span class="elsevierStyleItalic">Alphapolyomavirus</span> re&#250;ne esp&#233;cies de PyV que infectam humanos e animais&#44; incluindo os poliomav&#237;rus humanos &#40;HPyV&#41; 5 ou MCPyV&#44; HPyV8 ou poliomav&#237;rus associado a tricodisplasia spinulosa &#40;TSPyV&#41;&#44; HPyV9&#44; HPyV12 e HPyV13&#59; o g&#234;nero <span class="elsevierStyleItalic">Betapolyomavirus</span> conta com esp&#233;cies que infectam humanos e animais&#44; incluindo HPyV1 e HpyV4&#59; o g&#234;nero <span class="elsevierStyleItalic">Deltapolyomavirus</span> cont&#233;m os HPyV6&#44; HPyV7&#44; HPyV10 e HPyV11&#59; o g&#234;nero <span class="elsevierStyleItalic">Gammapolyomavirus</span>&#44; <span class="elsevierStyleItalic">Epsilonpolyomavirus</span> e <span class="elsevierStyleItalic">Zetapolyomavirus</span>&#44; descritos recentemente&#44; re&#250;nem outras esp&#233;cies que infectam mam&#237;feros e peixes&#44; somando&#8208;se ainda as esp&#233;cies de PyVs sem g&#234;nero definido &#40;<a class="elsevierStyleCrossRef" href="#fig0010">fig&#46; 2</a>&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0440"><span class="elsevierStyleSup">14&#44;16&#44;17</span></a></p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">At&#233; 2007&#44; somente duas esp&#233;cies haviam sido descritas como membros da fam&#237;lia que infectavam humanos&#58; o HPyV1 ou poliomav&#237;rus BK &#40;BKPyV&#41;&#44; e o HPyV2 ou John Cunningham poliomav&#237;rus ou V&#237;rus JC &#40;JCPyV&#41;&#46; Dessa data em diante&#44; em virtude da evolu&#231;&#227;o da tecnologia para sequenciamento gen&#233;tico&#44; outros 12 HPyV foram descritos e nomeados conforme a ordem cronol&#243;gica de sua descoberta&#44; totalizando as 14 esp&#233;cies que infectam humanos conhecidas atualmente &#40;<a class="elsevierStyleCrossRef" href="#fig0015">fig&#46; 3</a>&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0450"><span class="elsevierStyleSup">16&#8211;18</span></a></p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0040" class="elsevierStylePara elsevierViewall">Diversas dessas esp&#233;cies t&#234;m afinidade pelo tecido cut&#226;neo&#44; incluindo o HPyV6&#44; HPyV7&#44; HPyV9&#44; TSPyV e o MCPyV&#46;<a class="elsevierStyleCrossRefs" href="#bib0465"><span class="elsevierStyleSup">19&#8211;22</span></a> Sabe&#8208;se que doen&#231;as significantes causadas por PyV ocorrem em pacientes imunossuprimidos&#44; como leucoencefalopatia multifocal progressiva em pacientes com s&#237;ndrome da imunodefici&#234;ncia adquirida pelo JCPyV&#44; cistite hemorr&#225;gica em pacientes ap&#243;s transplante alog&#234;nico de c&#233;lulas&#8208;tronco hematopo&#233;ticas pelo BKPyV&#44; entre outros&#46; Cerca de 10&#37; dos pacientes transplantados renais desenvolvem nefropatia associada ao BKPyV&#44; com perda de fun&#231;&#227;o do enxerto em at&#233; 50&#37; dos casos da doen&#231;a&#46;<a class="elsevierStyleCrossRef" href="#bib0485"><span class="elsevierStyleSup">23</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Classifica&#231;&#227;o criada pela Ag&#234;ncia Internacional de Pesquisa em c&#226;ncer &#40;International Agency for Research on Cancer &#8211; IARC&#41; da Organiza&#231;&#227;o Mundial de Sa&#250;de &#40;OMS&#41; divide os agentes carcinog&#234;nicos em grupos&#44; separados pela sua maior ou menor a&#231;&#227;o carcinog&#234;nica em humanos&#44; baseados em evid&#234;ncia&#58; Grupo 1 como agentes carcinog&#234;nicos em humanos&#59; Grupo 2A como agentes provavelmente carcinog&#234;nicos em humanos&#59; Grupo 2B como agentes possivelmente carcinog&#234;nicos em humanos&#59; Grupo 3 como agentes n&#227;o relacionados &#224; carcinog&#234;nese em humanos&#46; Entre os agentes virais envolvidos ou potencialmente copart&#237;cipes na oncog&#234;nese&#44; encontram&#8208;se os HPyV&#44; notadamente o MCPyV&#46; Com base nessa classifica&#231;&#227;o da OMS&#44; o MCPyV foi classificado como sendo do Grupo 2A&#46;<a class="elsevierStyleCrossRefs" href="#bib0395"><span class="elsevierStyleSup">5&#44;24&#44;25</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">Evid&#234;ncias sorol&#243;gicas suportam a persist&#234;ncia da infec&#231;&#227;o pelos HPyV&#46; Pela medi&#231;&#227;o de anticorpos contra a prote&#237;na VP1 do caps&#237;dio viral&#44; pode&#8208;se inferir que a exposi&#231;&#227;o ao HPyV ocorre na inf&#226;ncia&#44; com aumento da soropreval&#234;ncia ao passar dos anos&#44; medindo&#8208;se n&#237;veis muito baixos at&#233; os 18 meses de vida e pr&#243;ximos dos 80&#37; aos 5 anos de idade&#46;<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">8</span></a> Ensaios sorol&#243;gicos realizados especificamente para o MCPyV tamb&#233;m confirmam essa onipresen&#231;a viral&#44; em que 80&#37; dos adultos apresentavam anticorpos contra o v&#237;rus&#46;<a class="elsevierStyleCrossRef" href="#bib0500"><span class="elsevierStyleSup">26</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">A presen&#231;a do DNA do MCPyV&#44; detectada em cargas virais vari&#225;veis pela t&#233;cnica de PCR&#44; tamb&#233;m tem sido descrita em diversos tecidos n&#227;o tumorais&#44; como na pele&#44; sangue perif&#233;rico&#44; tratos gastrintestinal&#44; respirat&#243;rio e urin&#225;rio&#44; gl&#226;ndula suprarrenal&#44; ba&#231;o&#44; medula &#243;ssea&#44; est&#244;mago&#44; ves&#237;cula biliar&#44; p&#226;ncreas&#44; cora&#231;&#227;o e aorta&#44; embora com &#237;ndice relativamente baixo de carga viral&#44; entre 0&#44;00026 e 0&#44;22 c&#243;pias por c&#233;lula&#46;<a class="elsevierStyleCrossRefs" href="#bib0505"><span class="elsevierStyleSup">27&#8211;30</span></a> Em m&#233;dia&#44; o n&#250;mero de c&#243;pias do genoma viral de MCPyV foi 60 vezes menor em tecidos saud&#225;veis quando comparados com amostras de CCM&#46;<a class="elsevierStyleCrossRef" href="#bib0510"><span class="elsevierStyleSup">28</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">Outro fator que refor&#231;a que a infec&#231;&#227;o pelo MCPyV seja onipresente e assintom&#225;tica &#233; o de que 60&#37; a 80&#37; da popula&#231;&#227;o eliminem continuamente o MCPyV atrav&#233;s da pele saud&#225;vel&#46;<a class="elsevierStyleCrossRef" href="#bib0525"><span class="elsevierStyleSup">31</span></a> Relatos recentes tamb&#233;m reportam que os fibroblastos presentes na derme podem suportar a replica&#231;&#227;o viral e podem ser c&#233;lulas hospedeiras genu&#237;nas para esse v&#237;rus&#46;<a class="elsevierStyleCrossRef" href="#bib0530"><span class="elsevierStyleSup">32</span></a></p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Carcinoma de c&#233;lulas de Merkel e poliomav&#237;rus de c&#233;lulas de Merkel</span><p id="par0065" class="elsevierStylePara elsevierViewall">Apesar de a oncogenicidade do PyV ser largamente relatada na literatura desde 1950&#44; a primeira descri&#231;&#227;o de PyV como agente etiol&#243;gico de neoplasia em humanos foi feita apenas em 2008&#44; com a descri&#231;&#227;o do MCPyV&#44; presente em cerca de 80&#37; dos casos de CCM e agente etiol&#243;gico desse tumor&#46;<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">8</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">O CCM &#233; neoplasia rara&#44; de origem possivelmente neuroend&#243;crina&#44; com curso agressivo&#44; e normalmente acomete pacientes de idade avan&#231;ada&#44; imunossuprimidos&#44; em locais de fotoexposi&#231;&#227;o cr&#244;nica&#46; A les&#227;o costuma se apresentar como p&#225;pula ou n&#243;dulo eritematoso&#44; de crescimento r&#225;pido e sem sintomas associados&#46; A maioria dessas les&#245;es apresenta tr&#234;s ou mais caracter&#237;sticas resumidas no acr&#244;nimo AEIOU&#58; A de &#8220;A<span class="elsevierStyleItalic">symptomatic nodule</span>&#8221; ou n&#243;dulo assintom&#225;tico&#59; E de &#8220;E<span class="elsevierStyleItalic">xpanding rapidly</span>&#8221; ou expans&#227;o r&#225;pida&#59; I de &#8220;I<span class="elsevierStyleItalic">mmunosuppressed host</span>&#8221; ou hospedeiro imunossuprimido&#59; O de &#8220;O<span class="elsevierStyleItalic">lder than age</span> 50&#8221; ou idade acima de 50 anos&#59; e U de &#8220;UV <span class="elsevierStyleItalic">exposed sites</span><span class="elsevierStyleItalic">or fair skin</span>&#8221; ou locais fotoexpostos aos raios ultravioletas &#40;UV&#41; ou pele clara<a class="elsevierStyleCrossRef" href="#bib0535"><span class="elsevierStyleSup">33</span></a> &#40;<a class="elsevierStyleCrossRef" href="#fig0020">fig&#46; 4</a>&#41;&#46;</p><elsevierMultimedia ident="fig0020"></elsevierMultimedia><p id="par0075" class="elsevierStylePara elsevierViewall">Apesar de as c&#233;lulas tumorais compartilharem caracter&#237;sticas morfol&#243;gicas e histol&#243;gicas com as c&#233;lulas de Merkel&#44; h&#225; um debate sobre a origem desse tumor&#46; Isso se deve ao fato de que as c&#233;lulas de Merkel s&#227;o p&#243;s&#8208;mit&#243;ticas&#44; estando em est&#225;gio de diferencia&#231;&#227;o terminal e n&#227;o realizando mitoses&#44; o que dificulta bastante a origem de um tumor&#46; Outro questionamento &#233; que o CCM raramente acomete os locais onde h&#225; c&#233;lulas de Merkel&#44; como palmas&#44; plantas&#44; leito ungueal e mucosa oral e genital&#46; Somam&#8208;se a esse fato a aus&#234;ncia de descri&#231;&#227;o de les&#245;es displ&#225;sicas ou precursoras desse tumor&#44; a localiza&#231;&#227;o das c&#233;lulas de Merkel na epiderme&#44; enquanto o CCM se localiza na derme&#44; a diferen&#231;a de fen&#243;tipos entre a c&#233;lula de Merkel e o CCM&#46; Desse modo&#44; postula&#8208;se que outras c&#233;lulas possam ser respons&#225;veis pela origem desse tumor&#44; e os poss&#237;veis candidatos incluem c&#233;lulas&#8208;tronco epid&#233;rmicas&#44; queratin&#243;citos &#40;as c&#233;lulas predominantes em todas as camadas de c&#233;lulas epid&#233;rmicas&#41;&#44; fibroblastos d&#233;rmicos&#44; c&#233;lulas pr&#243;&#8208;B ou c&#233;lulas pr&#233;&#8208;B &#40;<a class="elsevierStyleCrossRef" href="#fig0025">fig&#46; 5</a>&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0390"><span class="elsevierStyleSup">4&#44;33&#44;34</span></a></p><elsevierMultimedia ident="fig0025"></elsevierMultimedia><p id="par0080" class="elsevierStylePara elsevierViewall">Nessa rara neoplasia cut&#226;nea&#44; o DNA viral se integra clonalmente ao DNA da c&#233;lula hospedeira pelo resultado de muta&#231;&#227;o&#46; O padr&#227;o de integra&#231;&#227;o clonal do DNA do MCPyV ao DNA da c&#233;lula hospedeira sugere que a infe&#231;&#227;o viral ocorreu anteriormente &#224; expans&#227;o clonal das c&#233;lulas neopl&#225;sicas do CCM&#46;<a class="elsevierStyleCrossRef" href="#bib0445"><span class="elsevierStyleSup">15</span></a> Em adi&#231;&#227;o a essa muta&#231;&#227;o que causou a integra&#231;&#227;o clonal&#44; uma segunda muta&#231;&#227;o &#233; necess&#225;ria para o desenvolvimento dessa neoplasia&#44; o que justifica em parte a raridade dessa entidade&#46; A segunda muta&#231;&#227;o pode ser induzida pela exposi&#231;&#227;o aos raios UV e &#233; representada pela truncagem do LT&#8208;Ag do MCPyV&#46; Essa muta&#231;&#227;o&#44; em &#250;ltima an&#225;lise&#44; levar&#225; a uma inibi&#231;&#227;o da prote&#237;na supressora de tumor RB nessas c&#233;lulas infectadas&#44; acarretando no aumento dos fatores de transcri&#231;&#227;o E2F e desencadeamento da fase S do ciclo celular&#44; de maneira semelhante ao que ocorre no mecanismo de oncog&#234;nese pela oncoprote&#237;na E7 do HPV&#46; O LT&#8208;Ag tamb&#233;m contribui para a oncog&#234;nese por meio do est&#237;mulo &#224; angiog&#234;nese e &#224; atividade da telomerase&#44; al&#233;m da inibi&#231;&#227;o de vias intracelulares que levam &#224; apoptose&#46; O sT&#8208;Ag tamb&#233;m parece ter m&#250;ltiplas fun&#231;&#245;es oncog&#234;nicas e agiria em conjunto com o LT&#8208;Ag para a conclus&#227;o desse processo&#46;<a class="elsevierStyleCrossRef" href="#bib0545"><span class="elsevierStyleSup">35</span></a> Feng et al&#46;<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">8</span></a> descrevem a integra&#231;&#227;o do genoma do MCPyV ao genoma celular anteriormente &#224; expans&#227;o clonal das c&#233;lulas neopl&#225;sicas&#44; al&#233;m dessas muta&#231;&#245;es tumor&#8208;espec&#237;ficas de truncagem do LT&#8208;Ag&#46;<a class="elsevierStyleCrossRefs" href="#bib0410"><span class="elsevierStyleSup">8&#44;36</span></a> Tais muta&#231;&#245;es t&#234;m sido relatadas tamb&#233;m em uma parcela de leucemia linfoc&#237;tica cr&#244;nica<a class="elsevierStyleCrossRef" href="#bib0555"><span class="elsevierStyleSup">37</span></a> e c&#226;ncer de pulm&#227;o de c&#233;lulas n&#227;o pequenas&#46;<a class="elsevierStyleCrossRef" href="#bib0560"><span class="elsevierStyleSup">38</span></a> O genoma viral tamb&#233;m foi encontrado em c&#226;ncer de c&#233;lulas escamosas e adenocarcinomas cervicais<a class="elsevierStyleCrossRef" href="#bib0565"><span class="elsevierStyleSup">39</span></a> e leucemias linfoides&#44;<a class="elsevierStyleCrossRefs" href="#bib0570"><span class="elsevierStyleSup">40&#44;41</span></a> embora n&#227;o exista ainda comprova&#231;&#227;o etiol&#243;gica do MCPyV em malignidades diferentes de CCM&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">Estudos recentes t&#234;m dado maior relev&#226;ncia ao papel oncog&#234;nico do sT&#8208;Ag do que se pensava anteriormente&#46; Uma diferen&#231;a fundamental entre o MCPyV e outros PyV &#233; que o sT&#8208;Ag parece estar diretamente envolvido na transforma&#231;&#227;o neopl&#225;sica induzida por MCPyV no CCM&#46;<a class="elsevierStyleCrossRef" href="#bib0580"><span class="elsevierStyleSup">42</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">Liu et al&#46;&#44;<a class="elsevierStyleCrossRefs" href="#bib0530"><span class="elsevierStyleSup">32&#44;42</span></a> depois de examinar queratin&#243;citos epid&#233;rmicos&#44; fibroblastos d&#233;rmicos&#44; c&#233;lulas de Merkel e muitos outros tipos de c&#233;lulas na pele&#44; descobriram que apenas os fibroblastos d&#233;rmicos s&#227;o permissivos &#224; entrada&#44; transcri&#231;&#227;o e replica&#231;&#227;o do MCPyV&#46;<a class="elsevierStyleCrossRefs" href="#bib0530"><span class="elsevierStyleSup">32&#44;42</span></a> Esses fibroblastos&#44; quando tratados com fator de crescimento epid&#233;rmico e fator de crescimento b&#225;sico de fibroblastos&#44; foram particularmente eficazes no suporte &#224; infec&#231;&#227;o pelo MCPyV&#44; e como esses fatores de crescimento costumam ser tipicamente regulados positivamente em locais de feridas cut&#226;neas&#44; sugere&#8208;se que o processo de cicatriza&#231;&#227;o possa induzir um microambiente tecidual prop&#237;cio &#224; infec&#231;&#227;o e replica&#231;&#227;o do MCPyV&#46;<a class="elsevierStyleCrossRefs" href="#bib0530"><span class="elsevierStyleSup">32&#44;42</span></a></p><p id="par0095" class="elsevierStylePara elsevierViewall">Tem sido sugerido&#44; em estudos inicialmente realizados na popula&#231;&#227;o australiana&#44; que a participa&#231;&#227;o do MCPyV na g&#234;nese do CCM seja pouco frequente em tumores localizados em &#225;reas fotodanificadas de indiv&#237;duos de pele clara&#46;<a class="elsevierStyleCrossRef" href="#bib0585"><span class="elsevierStyleSup">43</span></a> Essa informa&#231;&#227;o &#233; corroborada pela menor frequ&#234;ncia de detec&#231;&#227;o do DNA viral em casos de CCM associados &#224; diferencia&#231;&#227;o escamosa&#44; que costuma ocorrer apenas em &#225;reas fotodanificadas&#44; levando &#224; hip&#243;tese de que haja uma via alternativa de oncog&#234;nese nesses tumores independente do v&#237;rus&#46;<a class="elsevierStyleCrossRefs" href="#bib0590"><span class="elsevierStyleSup">44&#44;45</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">A taxa de positividade viral vista em tumores de regi&#245;es com e sem fotoexposi&#231;&#227;o tamb&#233;m foi estudada por Dabner et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0600"><span class="elsevierStyleSup">46</span></a> utilizando&#8208;se como par&#226;metros histol&#243;gicos a elastose solar na derme e a displasia epid&#233;rmica como sinais de dano act&#237;nico cr&#244;nico&#46; Os resultados demonstram o mesmo padr&#227;o&#44; com menor presen&#231;a viral em tumores de &#225;reas fotoexpostas&#46; Em conson&#226;ncia&#44; Paik et al&#46;<a class="elsevierStyleCrossRef" href="#bib0595"><span class="elsevierStyleSup">45</span></a> tamb&#233;m demonstraram menor positividade do MCPyV em CCM por imuno&#8208;histoqu&#237;mica em indiv&#237;duos australianos&#44; com taxa de detec&#231;&#227;o de 7&#44;7&#37; &#40;3 em 39&#41; nos tumores localizados na cabe&#231;a e pesco&#231;o e de 24&#44;6&#37; &#40;16 em 65&#41; em outras localiza&#231;&#245;es do corpo&#46; Esses estudos refor&#231;am a possibilidade de que os tumores localizados em regi&#245;es fotoexpostas&#44; como cabe&#231;a e pesco&#231;o&#44; tenham outras vias de carcinog&#234;nese n&#227;o relacionadas &#224; presen&#231;a viral&#44; o que explicaria a baixa detec&#231;&#227;o por esse m&#233;todo nesses tumores&#46;<a class="elsevierStyleCrossRef" href="#bib0595"><span class="elsevierStyleSup">45</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">No entanto&#44; h&#225; estudos que apontam na dire&#231;&#227;o contr&#225;ria&#44; demonstrando maior presen&#231;a do DNA viral&#44; por meio da t&#233;cnica de PCR&#44; em CPNM de locais fotoexpostos&#46; Esse resultado levanta a hip&#243;tese de que a carcinog&#234;nese viral age como fator complementar &#224; carcinog&#234;nse induzida pela radia&#231;&#227;o UV&#46;<a class="elsevierStyleCrossRef" href="#bib0605"><span class="elsevierStyleSup">47</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">At&#233; o presente momento&#44; ainda n&#227;o existe um teste padr&#227;o&#8208;ouro para a detec&#231;&#227;o do MCPyV&#44; e mesmo a utiliza&#231;&#227;o combinada de PCR e imuno&#8208;histoqu&#237;mica &#40;IHQ&#41; tem resultados sub&#243;timos&#46;<a class="elsevierStyleCrossRef" href="#bib0610"><span class="elsevierStyleSup">48</span></a> Estudos anteriores que utilizaram as duas t&#233;cnicas combinadas para a detec&#231;&#227;o do MCPyV em CCM tiveram maior positividade com a t&#233;cnica de PCR&#44; o que sugere sua maior sensibilidade&#46;<a class="elsevierStyleCrossRefs" href="#bib0590"><span class="elsevierStyleSup">44&#44;49&#8211;52</span></a> No entanto&#44; outros autores descreveram a detec&#231;&#227;o do MCPyV em CCM com t&#233;cnicas combinadas em que houve maior detec&#231;&#227;o viral por meio da IHQ &#8211; os autores atribu&#237;ram esse achado &#224; grande diversidade de metodologias na t&#233;cnica de PCR para o MCPyV&#44; como utiliza&#231;&#227;o de <span class="elsevierStyleItalic">primer</span> com diferentes sequ&#234;ncias gen&#233;ticas&#44; n&#250;mero de conjuntos de <span class="elsevierStyleItalic">primers</span> do v&#237;rus detectado&#44; diferen&#231;as na sequ&#234;ncia humana de refer&#234;ncia que &#233; amplificada e os limites de corte usados para considerar um teste positivo&#46; &#201; poss&#237;vel que o ensaio de PCR mais sens&#237;vel e espec&#237;fico para detec&#231;&#227;o de MCPyV ainda n&#227;o tenha sido comparado com os ensaios de IHC&#46;<a class="elsevierStyleCrossRef" href="#bib0610"><span class="elsevierStyleSup">48</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">C&#226;ncer de pele n&#227;o melanoma e carcinoma de queratin&#243;citos relacionados ao poliomav&#237;rus de c&#233;lulas de Merkel</span><p id="par0115" class="elsevierStylePara elsevierViewall">O c&#226;ncer de pele n&#227;o melanoma &#40;CPNM&#41; ou CQ engloba basicamente todas as malignidades cut&#226;neas que n&#227;o se referem ao melanoma&#46; No entanto&#44; grande parte desses tumores correspondem ao carcinoma basocelular &#40;CBC&#41;&#44; ao carcinoma cut&#226;neo de c&#233;lulas escamosas ou carcinoma espinocelular &#40;CEC&#41; e suas variantes&#46;<a class="elsevierStyleCrossRef" href="#bib0635"><span class="elsevierStyleSup">53</span></a> O CQ n&#227;o inclui outros tipos de malignidades cut&#226;neas mais raras e com comportamentos distintos&#44; como o pr&#243;prio CCM&#44; o dermatofibrossarcoma&#44; linfomas cut&#226;neos&#44; carcinomas seb&#225;ceos&#44; angiossarcomas e outros tumores dos anexos cut&#226;neos&#46;<a class="elsevierStyleCrossRef" href="#bib0640"><span class="elsevierStyleSup">54</span></a></p><p id="par0120" class="elsevierStylePara elsevierViewall">Considerando o papel do MCPyV no desenvolvimento do CCM e sua detec&#231;&#227;o em diversos outros tecidos e tumores do corpo humano&#44; alguns pesquisadores come&#231;aram a investigar um poss&#237;vel papel etiol&#243;gico desse v&#237;rus na g&#234;nese de outros tumores&#44; majoritariamente em CQ&#46;<a class="elsevierStyleCrossRef" href="#bib0645"><span class="elsevierStyleSup">55</span></a> Na maioria desses estudos&#44;<a class="elsevierStyleCrossRefs" href="#bib0415"><span class="elsevierStyleSup">9&#8211;13</span></a> o DNA do MCPyV foi detectado pela t&#233;cnica de PCR&#44; havendo&#44; no entanto&#44; alguns estudos em que o LT&#8208;Ag tamb&#233;m foi investigado pela t&#233;cnica de IHQ&#44; demonstrando na maioria das vezes uma positividade menor do que na t&#233;cnica de PCR&#46;<a class="elsevierStyleCrossRef" href="#bib0645"><span class="elsevierStyleSup">55</span></a></p><p id="par0125" class="elsevierStylePara elsevierViewall">Kassem et al&#46;<a class="elsevierStyleCrossRef" href="#bib0420"><span class="elsevierStyleSup">10</span></a> demonstraram a presen&#231;a do MCPyV pela t&#233;cnica de PCR em 36 de 96 &#40;37&#44;5&#37;&#41; CBC acometendo pacientes imunocompetentes&#46; Em rela&#231;&#227;o aos CBC de pacientes imunossuprimidos&#44; os valores foram surpreendentemente altos&#44; positivos em 72&#44;2&#37; dos casos&#46; Os mesmos autores descrevem a presen&#231;a de MCPyV em 7 de 28 casos &#40;25&#37;&#41; de CEC em pacientes imunocompetentes&#46; Semelhante ao que ocorreu com os CBC&#44; o percentual subiu para 52&#37; em pacientes imunossuprimidos&#46; Tamb&#233;m foi descrita alta positividade na doen&#231;a de Bowen &#40;DB&#41;&#44; com 17&#44;4&#37; de positividade entre pacientes imunocompetentes e 69&#37; entre pacientes imunossuprimidos&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">Ainda em 2009&#44; Dworkin et al&#46;<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">9</span></a> descreveram positividade do MCPyV em 26 de 177 &#40;15&#37;&#41; CEC oriundos de pacientes imunocompetentes&#46;<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">9</span></a> Al&#233;m da positividade nos CEC&#44; tamb&#233;m se descreveu positividade de 17&#37; na pele adjacente ao tumor &#40;11 de 63 amostras&#41;&#46; Houve&#44; entre os casos pareados &#40;tumor e pele adjacente ao tumor&#41;&#44; uma concord&#226;ncia &#40;presen&#231;a ou aus&#234;ncia do DNA viral em ambos os esp&#233;cimes&#41; de 87&#37;&#46; Esse achado sugere que&#44; apesar da aus&#234;ncia de altera&#231;&#245;es histol&#243;gicas espec&#237;ficas&#44; o v&#237;rus j&#225; poderia estar presente na &#225;rea perilesional&#44; levando ao futuro desenvolvimento da les&#227;o tumoral&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">Zur Hausen et al&#46;<a class="elsevierStyleCrossRef" href="#bib0650"><span class="elsevierStyleSup">56</span></a> examinaram um total de 56 CQ oriundos de 11 pacientes imunossuprimidos &#40;25 CEC&#44; 13 DB e 18 CBC&#41; e 147 tumores oriundos de 125 pacientes imunocompetentes &#40;28 CEC&#44; 23 doen&#231;as de Bowen e 96 CBC&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0650"><span class="elsevierStyleSup">56</span></a> Houve detec&#231;&#227;o significantemente mais frequente de positividade para MCPyV nos tumores cut&#226;neos de pacientes imunossuprimidos nos tr&#234;s tipos de tumor&#44; com signific&#226;ncia estat&#237;stica &#40;p &#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#46; Todos os produtos de PCR tamb&#233;m foram sequenciados nesse estudo&#59; as muta&#231;&#245;es espec&#237;ficas do tumor na &#225;rea do LT&#8208;Ag n&#227;o puderam ser detectadas&#46; A carga viral tamb&#233;m foi analisada&#44; e na grande maioria dos CQ&#44; a carga viral do MCPyV estava bem abaixo dos casos de CCM positivos para MCPyV usados como controles&#46;<a class="elsevierStyleCrossRef" href="#bib0650"><span class="elsevierStyleSup">56</span></a></p><p id="par0140" class="elsevierStylePara elsevierViewall">Wieland et al&#46;<a class="elsevierStyleCrossRef" href="#bib0655"><span class="elsevierStyleSup">57</span></a> analisaram a presen&#231;a do MCPyV pela t&#233;cnica de PCR em 355 amostras de pele&#44; incluindo uma grande gama de CQ&#44; melanomas&#44; les&#245;es benignas e pele sadia perilesional&#46;<a class="elsevierStyleCrossRef" href="#bib0655"><span class="elsevierStyleSup">57</span></a> Houve positividade para a presen&#231;a viral em tr&#234;s dos 21 CBC &#40;14&#37;&#41;&#44; um de seis CEC &#40;17&#37;&#41;&#44; um de quatro doen&#231;as de Bowen &#40;25&#37;&#41;&#44; tr&#234;s de sete ceratoacantomas &#40;43&#37;&#41;&#44; dois de 12 melanomas &#40;17&#37;&#41;&#44; nenhum caso positivo em verrugas virais e ceratoses act&#237;nicas&#44; e oito de 34 casos de detec&#231;&#227;o em pele sadia perilesional &#40;24&#37;&#41;&#46; O DNA viral foi encontrado em 30 dos 34 casos de CCM utilizados como controle&#44; e com carga viral maior do que a encontrada nos CQ&#44; resultado similar ao descrito por Zur Hausen et al&#46;<a class="elsevierStyleCrossRefs" href="#bib0650"><span class="elsevierStyleSup">56&#44;57</span></a></p><p id="par0145" class="elsevierStylePara elsevierViewall">Garneski et al&#46;<a class="elsevierStyleCrossRef" href="#bib0585"><span class="elsevierStyleSup">43</span></a> encontraram uma taxa de 13&#37; de positividade do MCPyV em CEC&#44; em que duas das 15 les&#245;es de CEC estudadas albergavam o DNA viral&#46;<a class="elsevierStyleCrossRef" href="#bib0585"><span class="elsevierStyleSup">43</span></a> Em contrapartida&#44; Reisinger et al&#46;<a class="elsevierStyleCrossRef" href="#bib0660"><span class="elsevierStyleSup">58</span></a> pesquisaram a positividade do LT&#8208;Ag por IHQ&#44; utilizando o anticorpo CM2B4 em 20 pacientes com CCM e em alguns CBC e CEC oriundos desses mesmos pacientes&#46; Um total de 12 desses pacientes apresentavam CBC e CEC que se desenvolveram ap&#243;s a detec&#231;&#227;o do CCM&#59; a pesquisa do LT&#8208;Ag por IHQ utilizando o anticorpo monoclonal CM2B4 veio negativa em todos os 12 casos&#46; De maneira oposta&#44; esses pacientes tinham alta positividade de 92&#37; &#40;11 em 12&#41; para o LT&#8208;Ag visto por IHQ em seus CCM&#46;<a class="elsevierStyleCrossRef" href="#bib0660"><span class="elsevierStyleSup">58</span></a> Rollison et al&#46;<a class="elsevierStyleCrossRef" href="#bib0665"><span class="elsevierStyleSup">59</span></a> descreveram um percentual de 38&#37; de positividade do MCPyV DNA em amostras de tecido congelado fresco de CEC obtidos de pacientes imunocompetentes&#46; A presen&#231;a do MCPyV DNA se associou a altos n&#237;veis de anticorpos anti&#8208;MCPyV circulantes&#46;<a class="elsevierStyleCrossRef" href="#bib0665"><span class="elsevierStyleSup">59</span></a> Esse expressivo percentual em pacientes imunocompetentes pode ser decorrente do fato de as amostras terem sido estudadas imediatamente ap&#243;s sua retirada e n&#227;o ap&#243;s processamento do material em blocos de parafina&#44; evitando a poss&#237;vel degrada&#231;&#227;o parcial do material gen&#233;tico presente&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">Em conson&#226;ncia com esses estudos&#44; Mertz et al&#46;<a class="elsevierStyleCrossRef" href="#bib0670"><span class="elsevierStyleSup">60</span></a> detectaram o DNA do MCPyV por PCR em dois &#40;10&#37;&#41; de 20 pacientes com DB&#46; Em um desses pacientes&#44; que era imunossuprimido por transplante renal&#44; foram tamb&#233;m avaliadas diversas outras les&#245;es cut&#226;neas&#44; com positividade para o MCPyV em quatro de quatro verrugas virais &#40;100&#37;&#41;&#44; tr&#234;s de seis doen&#231;as de Bowen &#40;50&#37;&#41;&#44; e duas de tr&#234;s ceratoses seborreicas &#40;66&#44;6&#37;&#41;&#46; Em uma segunda coorte realizada em pacientes imunossuprimidos e submetidos a transplante renal&#44; o DNA do MCPyV foi encontrado em uma de 16 verrugas virais &#40;6&#44;3&#37;&#41;&#44; em duas de 21 Doen&#231;as de Bowen &#40;9&#44;5&#37;&#41;&#46; Em indiv&#237;duos imunocompetentes&#44; o DNA do MCPyV foi encontrado em duas das 30 verrugas virais &#40;6&#44;7&#37;&#41; e em duas das 24 Doen&#231;as de Bowen &#40;8&#44;3&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0670"><span class="elsevierStyleSup">60</span></a></p><p id="par0155" class="elsevierStylePara elsevierViewall">Os mesmos pesquisadores&#44;<a class="elsevierStyleCrossRef" href="#bib0435"><span class="elsevierStyleSup">13</span></a> em 2013&#44; encontraram positividade para o v&#237;rus em 28 de 71 &#40;39&#44;4&#37;&#41; CBC retirados de pacientes imunocompetentes&#46; Essa taxa subiu para 47&#44;1&#37; em imunossuprimidos&#44; em que oito de 17 CBC albergavam o DNA viral&#46; Em contraste com a frequente detec&#231;&#227;o viral por PCR nese estudo&#44; a IHQ para a pesquisa do LT&#8208;Ag no tecido tumoral foi positiva apenas em dois dos 17 casos de CBC que acometiam pacientes imunossuprimidos&#44; e negativa em todos CBC dos pacientes imunocompetentes&#46;<a class="elsevierStyleCrossRef" href="#bib0435"><span class="elsevierStyleSup">13</span></a> Nesse mesmo ano&#44; Murakami et al&#46;<a class="elsevierStyleCrossRef" href="#bib0675"><span class="elsevierStyleSup">61</span></a> encontraram quatro de 30 &#40;13&#37;&#41; CEC positivos para MCPyV&#59; desses quatro&#44; dois tamb&#233;m eram positivos para LT&#8208;Ag pela IHQ&#46; Tamb&#233;m foi descrito no mesmo estudo uma total negatividade para a presen&#231;a do MCPyV pela PCR em 10 casos de CBC&#44; n&#227;o obstante o fato do pequeno n&#250;mero total de casos dificultar a an&#225;lise&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">Becker et al&#46;&#44; ap&#243;s confirmarem a presen&#231;a do MCPyV em 45 de 53 &#40;84&#44;9&#37;&#41; pacientes com CCM&#44; descreveram positividade viral em tr&#234;s de 24 &#40;12&#44;5&#37;&#41; casos de CBC&#46;<a class="elsevierStyleCrossRef" href="#bib0680"><span class="elsevierStyleSup">62</span></a></p><p id="par0165" class="elsevierStylePara elsevierViewall">Neto et al&#46;<a class="elsevierStyleCrossRef" href="#bib0680"><span class="elsevierStyleSup">62</span></a> tamb&#233;m fizeram an&#225;lise recente entre a presen&#231;a de MCPyV e tumores cut&#226;neos&#44; analisando 10 casos de CBC e 10 de CEC&#46; Pela t&#233;cnica de PCR com extra&#231;&#227;o do material gen&#233;tico de material guardado em bloco de parafina&#44; foi detectado material gen&#233;tico do MCPyV em quatro dos 20 casos&#44; em compara&#231;&#227;o com a presen&#231;a em 100&#37; dos 20 casos de CCM analisados tamb&#233;m nesse estudo&#46;<a class="elsevierStyleCrossRef" href="#bib0685"><span class="elsevierStyleSup">63</span></a></p><p id="par0170" class="elsevierStylePara elsevierViewall">Ridd et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0685"><span class="elsevierStyleSup">63</span></a> ap&#243;s investigarem a presen&#231;a do DNA do MCPyV por PCR em 85 casos de CEC&#44; 37 ceratoacantomas&#44; 28 doen&#231;as de Bowen e seis ceratoses act&#237;nicas&#44; encontraram positividade apenas em um caso de ceratoacantoma&#46; A t&#233;cnica de PCR desse estudo foi validada em uma coorte de CCM&#44; que demonstrou 54&#37; &#40;7&#47;13&#41; dos tumores positivos para a presen&#231;a do MCPyV&#46;<a class="elsevierStyleCrossRef" href="#bib0690"><span class="elsevierStyleSup">64</span></a></p><p id="par0175" class="elsevierStylePara elsevierViewall">Kaibuchi&#8208;Noda et al&#46;<a class="elsevierStyleCrossRef" href="#bib0695"><span class="elsevierStyleSup">65</span></a> descreveram um relato de caso em que um paciente imunossuprimido&#44; um ano ap&#243;s ter CEC ressecado&#44; apresentou met&#225;stases diagnosticadas como CCM&#44; tendo realizado a pesquisa do DNA do MCPyV por PCR e do LT&#8208;Ag por IHQ&#46;<a class="elsevierStyleCrossRef" href="#bib0695"><span class="elsevierStyleSup">65</span></a> O estudo revelou que o DNA do MCPyV foi detectado na les&#227;o de CEC&#44; indicando que a infec&#231;&#227;o pelo MCPyV ocorrera pelo menos um ano antes da ocorr&#234;ncia de CCM metast&#225;tico&#46; No entanto&#44; o n&#250;mero de c&#243;pias do MCPyV por c&#233;lula na les&#227;o de CCM foi maior que na de CEC&#44; e a pesquisa do LT&#8208;Ag pela IHQ foi positiva apenas no CCM&#44; colocando em d&#250;vida se houve participa&#231;&#227;o efetiva do MCPyV na g&#234;nese de ambos os tumores ou se apenas no CCM&#46;<a class="elsevierStyleCrossRef" href="#bib0695"><span class="elsevierStyleSup">65</span></a></p><p id="par0180" class="elsevierStylePara elsevierViewall">Estudos recentes tamb&#233;m indicam a presen&#231;a de outros HPyV em ceratoacantomas e outros CQ&#46; Beckervordersandforth et al&#46;<a class="elsevierStyleCrossRef" href="#bib0700"><span class="elsevierStyleSup">66</span></a> descreveram a presen&#231;a do HPyV6 por PCR em diversos tumores inclu&#237;dos no grupo de CPNM&#59; 25 dos 59 &#40;42&#44;3&#37;&#41; dos ceratoacantomas apresentavam material gen&#233;tico&#44; assim como 23 dos 109 &#40;21&#44;1&#37;&#41; casos de CBC e oito dos 86 &#40;9&#44;3&#37;&#41; casos de CCE&#46;<a class="elsevierStyleCrossRef" href="#bib0700"><span class="elsevierStyleSup">66</span></a></p><p id="par0185" class="elsevierStylePara elsevierViewall">A presen&#231;a do HPyV6&#44; assim como a de outros HPyV&#44; como o MCPyV&#44; TSPyV&#44; HPyV6&#44; HPyV7&#44; HPyV9 e HPyV10&#44; tamb&#233;m foi investigada em CEC de pacientes com melanoma em tratamento com inibidores de BRAF&#46;<a class="elsevierStyleCrossRef" href="#bib0705"><span class="elsevierStyleSup">67</span></a> At&#233; o momento&#44; os &#250;nicos fatores identificados que contribuem para o desenvolvimento de CEC nesses pacientes s&#227;o muta&#231;&#245;es nos genes <span class="elsevierStyleItalic">RAS</span>&#46; No entanto&#44; essas muta&#231;&#245;es explicam apenas 60&#37; dos tumores&#46; &#201; importante identificar o que est&#225; causando os tumores remanescentes&#46; Dezoito amostras de biopsia de seis pacientes foram avaliadas&#44; 10 &#40;62&#37;&#41; das 16 amostras continham muta&#231;&#245;es RAS&#59; o DNA de HPyV9&#44; HPyV10 e TSPyV estava ausente nas amostras&#44; o DNA do MCPyV estava presente em 13 das 18 amostras &#40;72&#44;22&#37;&#41;&#59; e o DNA do HPV&#44; HPyV6 e HPyV7 estava presente em todas as amostras&#46; Em geral&#44; a carga viral encontrada nesse estudo foi baixa&#44; com exce&#231;&#227;o do HPyV6&#44; que tamb&#233;m foi detectado por IHQ com os ant&#237;genos da prote&#237;na central VP1&#46;<a class="elsevierStyleCrossRef" href="#bib0705"><span class="elsevierStyleSup">67</span></a> Haeggblom et al&#46; descreveram a presen&#231;a de PyV em ceratoacantomas e nevos de Spitz e&#44; apesar de n&#227;o haver predomin&#226;ncia de nenhuma esp&#233;cie espec&#237;fica&#44; foi encontrado material gen&#233;tico viral pela t&#233;cnica de PCR em 20 de 47 les&#245;es dessas afec&#231;&#245;es&#46;<a class="elsevierStyleCrossRef" href="#bib0710"><span class="elsevierStyleSup">68</span></a></p><p id="par0190" class="elsevierStylePara elsevierViewall">Estudo realizado por Toptan et al&#46;<a class="elsevierStyleCrossRef" href="#bib0715"><span class="elsevierStyleSup">69</span></a> investigou&#44; por meio de um anticorpo utilizado na t&#233;cnica de IHQ que detecta simultaneamente uma ampla gama de HPyV&#44; incluindo o MCPyV&#44; a presen&#231;a desse v&#237;rus em centenas de tumores&#44; dentre eles o CBC e o CEC&#46; N&#227;o foi detectada presen&#231;a do MCPyV nesses carcinomas cut&#226;neos&#44; e raras c&#233;lulas marcadas com esse anticorpo em alguns tumores espor&#225;dicos foi interpretado como infec&#231;&#227;o passageira e incidental&#46;<a class="elsevierStyleCrossRef" href="#bib0715"><span class="elsevierStyleSup">69</span></a></p><p id="par0195" class="elsevierStylePara elsevierViewall">Estudando 96 les&#245;es cut&#226;neas&#44; Bellott et al&#46;<a class="elsevierStyleCrossRef" href="#bib0430"><span class="elsevierStyleSup">12</span></a> detectaram a presen&#231;a do MCPyV em 31&#37; desses casos&#44; dos quais 23 &#40;33&#44;3&#37;&#41; dentre os 69 casos de CBC&#44; dois dos 11 CEC &#40;18&#37;&#41;&#44; duas das quatro doen&#231;as de Bowen &#40;50&#37;&#41; e&#44; dentre as outras 11 les&#245;es cut&#226;neas&#44; quatro &#40;36&#44;3&#37;&#41; foram positivos para o DNA viral &#40;duas ceratoses act&#237;nicas&#44; um dermatofibrosarcoma e um ceratoacantoma&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0430"><span class="elsevierStyleSup">12</span></a> Estudo mais recente pelo mesmo autor&#44;<a class="elsevierStyleCrossRef" href="#bib0720"><span class="elsevierStyleSup">70</span></a> dessa vez analisando a presen&#231;a do genoma viral do MCPyV pela t&#233;cnica de PCR e do LT&#8208;Ag maior pela t&#233;cnica de IHQ&#44; teve 103 amostras de CQ de 91 pacientes analisadas&#46; Quarenta e quatro &#40;42&#44;7&#37;&#41; tumores foram positivos para o v&#237;rus via PCR&#44; 34 de 85 &#40;40&#37;&#41; no grupo CBC&#44; seis de 12 &#40;50&#37;&#41; no CEC&#44; dois de quatro &#40;50&#37;&#41; para DB e um de dois &#40;50&#37;&#41; para ceratoacantoma&#46; O resultado da IHQ mostra positividade total em 18 casos &#40;17&#44;7&#37;&#41;&#44; sete casos de positividade apenas no tumor &#40;6&#44;9&#37;&#41;&#44; oito no infiltrado peritumoral &#40;7&#44;9&#37;&#41; e tr&#234;s em ambos &#40;3&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0720"><span class="elsevierStyleSup">70</span></a></p><p id="par0200" class="elsevierStylePara elsevierViewall">Costa et al&#46;<a class="elsevierStyleCrossRef" href="#bib0725"><span class="elsevierStyleSup">71</span></a> tamb&#233;m realizaram a pesquisa de diversos HPyV por meio da t&#233;cnica de PCR em tecidos cut&#226;neos&#44; incluindo casos de CQ&#44; melanoma&#44; sarcoma de Kaposi&#44; CCM e pele normal&#46; O MCPyV foi o HPyV mais encontrado&#44; presente em dois de 20 &#40;10&#37;&#41; CBC e tr&#234;s de 20 &#40;15&#37;&#41; CEC&#44; al&#233;m de n&#227;o estar presente em um total de 20 casos de pele normal&#46;<a class="elsevierStyleCrossRef" href="#bib0725"><span class="elsevierStyleSup">71</span></a></p><p id="par0205" class="elsevierStylePara elsevierViewall">Os principais estudos que investigaram a presen&#231;a de part&#237;culas virais do MCPyV em CQ se encontram reunidos em ordem cronol&#243;gica na <a class="elsevierStyleCrossRef" href="#tbl0005">tabela 1</a>&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Discuss&#227;o</span><p id="par0210" class="elsevierStylePara elsevierViewall">Existem muitas suposi&#231;&#245;es para a varia&#231;&#227;o da preval&#234;ncia do MCPyV nos CQ entre diferentes estudos e as diverg&#234;ncias desses resultados com os de IHQ&#46;</p><p id="par0215" class="elsevierStylePara elsevierViewall">A detec&#231;&#227;o do DNA do MCPyV pela t&#233;cnica de PCR pode ser afetada pelos <span class="elsevierStyleItalic">primers</span> que foram usados&#46; De fato&#44; a maioria dos estudos aplicou os <span class="elsevierStyleItalic">primers</span> LT&#8208;Ag originalmente usados por Feng et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">8</span></a> considerados superiores aos <span class="elsevierStyleItalic">primers</span> direcionados contra a VP1&#46;<a class="elsevierStyleCrossRef" href="#bib0645"><span class="elsevierStyleSup">55</span></a></p><p id="par0220" class="elsevierStylePara elsevierViewall">A qualidade das amostras tamb&#233;m pode afetar o resultado da rea&#231;&#227;o de PCR&#44; pois v&#225;rios estudos relataram que a detec&#231;&#227;o do DNA do MCPyV em tecidos frescos congelados &#233; mais confi&#225;vel quando em compara&#231;&#227;o com a detec&#231;&#227;o em amostras fixadas na parafina&#46;<a class="elsevierStyleCrossRef" href="#bib0645"><span class="elsevierStyleSup">55</span></a></p><p id="par0225" class="elsevierStylePara elsevierViewall">O DNA viral &#233; extra&#237;do de um fragmento do tumor&#44; tendo acesso a somente um subgrupo das c&#233;lulas presentes na neoplasia&#46; H&#225; a possibilidade de que haja part&#237;culas virais presentes em locais do tumor que n&#227;o tenham sido analisados em conjunto pela PCR e pela IHQ&#46; O tumor &#233; composto por diversas linhagens celulares heterog&#234;neas que cont&#234;m c&#233;lulas tumorais&#44; infiltrados celulares imunes como de linf&#243;citos&#44; c&#233;lulas endoteliais e fibroblastos associados ao c&#226;ncer&#46; Sabendo que os fibroblastos podem suportar a replica&#231;&#227;o viral e podem ser c&#233;lulas hospedeiras genu&#237;nas para esse v&#237;rus&#44;<a class="elsevierStyleCrossRef" href="#bib0530"><span class="elsevierStyleSup">32</span></a> e tamb&#233;m que os mon&#243;citos infiltrados podem ser reservat&#243;rios para o v&#237;rus&#44;<a class="elsevierStyleCrossRef" href="#bib0730"><span class="elsevierStyleSup">72</span></a> produtos de PCR positivos podem derivar de infec&#231;&#227;o viral nessas c&#233;lulas&#46;</p><p id="par0230" class="elsevierStylePara elsevierViewall">M&#233;todos baseados em PCR tamb&#233;m s&#227;o propensos &#224; contamina&#231;&#227;o&#44; j&#225; que se postula que o MCPyV seja eliminado cronicamente pela pele&#44; podendo fazer parte de sua microbiota&#59;<a class="elsevierStyleCrossRef" href="#bib0735"><span class="elsevierStyleSup">73</span></a> a contamina&#231;&#227;o durante a coleta no manuseio das amostras n&#227;o pode ser exclu&#237;da&#46;</p><p id="par0235" class="elsevierStylePara elsevierViewall">A detec&#231;&#227;o simult&#226;nea do LT&#8208;Ag pela IHQ e do seu material gen&#233;tico por PCR nesses tecidos tumorais pode demonstrar evid&#234;ncias de uma participa&#231;&#227;o ativa do v&#237;rus na manuten&#231;&#227;o do crescimento cancer&#237;geno&#44; e todos esses estudos demonstram que&#44; para ajudar a elucidar se o MCPyV est&#225; realmente associado &#224; g&#234;nese dos CQ&#44; mais estudos epidemiol&#243;gicos ainda s&#227;o necess&#225;rios&#46;<a class="elsevierStyleCrossRef" href="#bib0735"><span class="elsevierStyleSup">73</span></a></p><p id="par0240" class="elsevierStylePara elsevierViewall">Outras etapas que s&#227;o ainda importantes para a elucida&#231;&#227;o dessa quest&#227;o entre o poss&#237;vel papel etiol&#243;gico do MCPyV em tumores outros que n&#227;o o CCM&#44; s&#227;o&#58;</p><p id="par0245" class="elsevierStylePara elsevierViewall">O estado do genoma do v&#237;rus deve ser determinado&#44; se episomal ou integrado&#44; j&#225; que a integra&#231;&#227;o do genoma viral parece ser um pr&#233;&#8208;requisito para o desenvolvimento do processo neopl&#225;sico associado a esse v&#237;rus&#59;<a class="elsevierStyleCrossRef" href="#bib0645"><span class="elsevierStyleSup">55</span></a></p><p id="par0250" class="elsevierStylePara elsevierViewall">O gene que codifica o LT&#8208;Ag deve ser sequenciado para determinar se h&#225; a express&#227;o das muta&#231;&#245;es tumor&#8208;espec&#237;ficas de do LT&#8208;Ag truncado&#59;<a class="elsevierStyleCrossRef" href="#bib0645"><span class="elsevierStyleSup">55</span></a></p><p id="par0255" class="elsevierStylePara elsevierViewall">Hibridiza&#231;&#227;o <span class="elsevierStyleItalic">in situ</span> para o DNA ou RNA viral deve ser feita para garantir que as sequ&#234;ncias virais sejam detectadas em c&#233;lulas tumorais e n&#227;o em outros tipos de c&#233;lulas adjacentes ao tumor&#46;<a class="elsevierStyleCrossRef" href="#bib0645"><span class="elsevierStyleSup">55</span></a></p><p id="par0260" class="elsevierStylePara elsevierViewall">Amostras de tumor em diferentes est&#225;dios de desenvolvimento tamb&#233;m devem ser examinadas&#44; j&#225; que o v&#237;rus pode estar envolvido apenas no in&#237;cio do processo neopl&#225;sico&#44; n&#227;o sendo necess&#225;rio para a progress&#227;o do tumor&#46;<a class="elsevierStyleCrossRef" href="#bib0645"><span class="elsevierStyleSup">55</span></a> De fato&#44; um mecanismo de ataque e fuga para a a&#231;&#227;o oncog&#234;nica do MCPyV em alguns casos de CCM foi sugerido por Houben et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0740"><span class="elsevierStyleSup">74</span></a> no qual a oncog&#234;nese viral s&#243; seria essencial para desencadear o in&#237;cio do processo&#46;<a class="elsevierStyleCrossRef" href="#bib0740"><span class="elsevierStyleSup">74</span></a></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Conclus&#227;o</span><p id="par0265" class="elsevierStylePara elsevierViewall">Diversas informa&#231;&#245;es&#44; como a alta soropreval&#234;ncia de MCPyV na popula&#231;&#227;o humana&#44; os potenciais oncog&#234;nicos <span class="elsevierStyleItalic">in vitro</span> do LT&#8208;Ag e do sT&#8208;Ag e seu papel etiol&#243;gico no CCM&#44; sugerem que o MCPyV pode desempenhar um papel&#44; de maneira isolada ou em associa&#231;&#227;o com outros fatores&#44; em outros tipos de c&#226;ncer no homem&#44; especialmente em indiv&#237;duos com sistema imunol&#243;gico comprometido&#59; entretanto&#44; essa rela&#231;&#227;o causal entre o MCPyV e CQ ainda n&#227;o pode ser estabelecida&#46;<a class="elsevierStyleCrossRef" href="#bib0645"><span class="elsevierStyleSup">55</span></a></p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Suporte financeiro</span><p id="par0270" class="elsevierStylePara elsevierViewall">O presente estudo faz parte da tese de doutorado do autor principal e foi contemplado com bolsa de pesquisa do FUNADERM &#40;Fundo de Apoio &#224; Dermatologia&#41;&#44; &#243;rg&#227;o da Sociedade Brasileira de Dermatologia&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Contribui&#231;&#227;o dos autores</span><p id="par0275" class="elsevierStylePara elsevierViewall">Thiago Rubim Bellott&#58; Concep&#231;&#227;o e o desenho do estudo&#59; levantamento dos dados&#44; ou an&#225;lise e interpreta&#231;&#227;o dos dados&#59; reda&#231;&#227;o do artigo ou revis&#227;o cr&#237;tica do conte&#250;do intelectual importante&#59; obten&#231;&#227;o&#44; an&#225;lise e interpreta&#231;&#227;o dos dados&#59; participa&#231;&#227;o efetiva na orienta&#231;&#227;o da pesquisa&#59; participa&#231;&#227;o intelectual em conduta proped&#234;utica e&#47;ou terap&#234;utica de casos estudados&#59; revis&#227;o cr&#237;tica da literatura&#59; aprova&#231;&#227;o final da vers&#227;o final do manuscrito&#46;</p><p id="par0280" class="elsevierStylePara elsevierViewall">Fl&#225;vio Barbosa Luz&#58; Concep&#231;&#227;o e o desenho do estudo&#59; reda&#231;&#227;o do artigo ou revis&#227;o cr&#237;tica do conte&#250;do intelectual importante&#59; obten&#231;&#227;o&#44; an&#225;lise e interpreta&#231;&#227;o dos dados&#59; participa&#231;&#227;o efetiva na orienta&#231;&#227;o da pesquisa&#59; participa&#231;&#227;o intelectual em conduta proped&#234;utica e&#47;ou terap&#234;utica de casos estudados&#59; aprova&#231;&#227;o final da vers&#227;o final do manuscrito&#46;</p><p id="par0285" class="elsevierStylePara elsevierViewall">Anna Karolinne Fausto&#58; Participa&#231;&#227;o efetiva na orienta&#231;&#227;o da pesquisa&#59; participa&#231;&#227;o intelectual em conduta proped&#234;utica e&#47;ou terap&#234;utica de casos estudados&#59; aprova&#231;&#227;o final da vers&#227;o final do manuscrito&#46;</p><p id="par0290" class="elsevierStylePara elsevierViewall">Rafael Brand&#227;o Varella&#58; Participa&#231;&#227;o efetiva na orienta&#231;&#227;o da pesquisa&#59; participa&#231;&#227;o intelectual em conduta proped&#234;utica e&#47;ou terap&#234;utica de casos estudados&#59; aprova&#231;&#227;o final da vers&#227;o final do manuscrito&#46;</p><p id="par0295" class="elsevierStylePara elsevierViewall">Mayra Carrijo Rochael&#59; Participa&#231;&#227;o efetiva na orienta&#231;&#227;o da pesquisa&#59; participa&#231;&#227;o intelectual em conduta proped&#234;utica e&#47;ou terap&#234;utica de casos estudados&#59; aprova&#231;&#227;o final da vers&#227;o final do manuscrito&#46;</p><p id="par0300" class="elsevierStylePara elsevierViewall">Luciana Pantale&#227;o&#58; Participa&#231;&#227;o efetiva na orienta&#231;&#227;o da pesquisa&#59; participa&#231;&#227;o intelectual em conduta proped&#234;utica e&#47;ou terap&#234;utica de casos estudados&#59; aprova&#231;&#227;o final da vers&#227;o final do manuscrito&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Conflito de interesses</span><p id="par0305" class="elsevierStylePara elsevierViewall">Nenhum&#46;</p></span></span>"
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          "titulo" => "C&#226;ncer de pele n&#227;o melanoma e carcinoma de queratin&#243;citos relacionados ao poliomav&#237;rus de c&#233;lulas de Merkel"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">V&#237;rus t&#234;m sido frequentemente identificados em diversas neoplasias humanas&#44; embora seu papel etiol&#243;gico em alguns tumores ainda seja motivo de controv&#233;rsia&#46; Os principais v&#237;rus com capacidade oncog&#234;nica s&#227;o os poliomav&#237;rus&#44; especificamente o poliomav&#237;rus de c&#233;lulas de Merkel &#40;MCPyV&#41;&#46; Revis&#245;es recentes na taxonomia dos poliomav&#237;rus dividiram a fam&#237;lia Polyomaviridae em seis g&#234;neros&#44; incluindo 117 esp&#233;cies&#44; com um total de 14 esp&#233;cies que infectam humanos atualmente conhecidas&#46; Apesar de a oncogenicidade do poliomav&#237;rus ser largamente relatada na literatura desde 1950&#44; a primeira descri&#231;&#227;o de poliomav&#237;rus como agente etiol&#243;gico de neoplasia em humanos foi feita apenas em 2008&#44; com a descri&#231;&#227;o do MCPyV&#44; presente em cerca de 80&#37; dos casos de carcinoma de c&#233;lulas Merkel &#40;CCM&#41;&#44; com a integra&#231;&#227;o de seu genoma ao das c&#233;lulas tumorais e muta&#231;&#245;es tumor&#8208;espec&#237;ficas&#44; sendo considerado o agente etiol&#243;gico dessa neoplasia desde ent&#227;o&#46; O MCPyV tamb&#233;m j&#225; foi detectado em carcinomas de queratin&#243;citos&#44; como o carcinoma basocelular e o carcinoma de c&#233;lulas escamosas da pele em indiv&#237;duos com e sem imunossupress&#227;o&#46; Dados sobre a ocorr&#234;ncia de viroses oncog&#234;nicas e potencialmente envolvidas na oncog&#234;nese&#44; que causam persist&#234;ncia e inj&#250;ria tecidual&#44; relacionados ao poliomav&#237;rus de c&#233;lulas de Merkel ainda s&#227;o escassos&#44; permanecendo em aberto a hip&#243;tese de que o poliomav&#237;rus de c&#233;lulas de Merkel possa ter papel relevante na g&#234;nese de outros carcinomas cut&#226;neos al&#233;m do CCM&#46; Portanto&#44; o artigo se prop&#245;e ao aprofundamento no estado atual de conhecimento sobre a presen&#231;a do MCPyV em carcinomas de queratin&#243;citos&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0025">Como citar este artigo&#58; Bellott TR&#44; Luz FB&#44; Silva AKF&#44; Varella RB&#44; Rochael MC&#44; Pantale&#227;o L&#46; Merkel cell polyomavirus and its etiological relationship with skin tumors&#46; An Bras Dermatol&#46; 2023&#59;98&#58;737&#8211;49&#46;</p>"
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          "pt" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Genoma do MCPyV&#58; regi&#227;o controle n&#227;o codificante &#40;NCCR&#44; <span class="elsevierStyleItalic">non coding control region</span>&#41;&#59; regi&#227;o de codifica&#231;&#227;o inicial <span class="elsevierStyleItalic">&#40;early region&#41;&#44;</span> que codifica os ant&#237;geno&#8208;T maior &#40;LT&#8208;Ag&#41; e T&#8208;small &#40;sT&#8208;Ag&#41;&#59; e regi&#227;o de codifica&#231;&#227;o tardia <span class="elsevierStyleItalic">&#40;late region&#41;&#46;</span> LT&#8208;Ag&#44; <span class="elsevierStyleItalic">Large T&#8208;antigen</span> ou ant&#237;geno&#8208;T maior&#59; sT&#8208;Ag&#44; s<span class="elsevierStyleItalic">mall&#8208;T antigen</span> ou ant&#237;geno&#8208;T menor&#59; RCNC&#44; regi&#227;o controle n&#227;o codificante ou <span class="elsevierStyleItalic">non&#8208;coding control region</span>&#59; VP1 e VP2&#44; prote&#237;na do caps&#237;dio viral 1 e 2&#46; Fonte&#58; reproduzida de Liu W et al&#46;&#44; 2016&#46;<a class="elsevierStyleCrossRef" href="#bib0445"><span class="elsevierStyleSup">15</span></a></p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Autores&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Tecidos investigados&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">PCR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Resultado&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">IHQ&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Resultado&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Kassem et al&#46;&#44; 2009</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CBC&#44; CEC&#44; DB</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sim&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CBC IS&#58; 13 de 18 &#40;72&#44;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#42;<span class="elsevierStyleItalic">Primers</span> para LT3 e VP1</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CEC IS&#58; 13 de 25 &#40;52&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">DB IS&#58; 9 de 13 &#40;69&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CBC IC&#58; 36 de 96 &#40;37&#44;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CEC IC&#58; 7 de 28 &#40;25&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">DB IC&#58; 4 de 23 &#40;17&#44;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dworkin et al&#46;&#44; 2009&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CEC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sim&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CEC IC&#58; 26 de 177 &#40;15&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#42;<span class="elsevierStyleItalic">Primers</span> para LT3 e VP1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Pele adjacente ao CEC&#58; 11 de 63 &#40;17&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Zur Hausen et al&#46;&#44; 2009&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sim&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">18 CBC IS<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#42;&#42;<span class="elsevierStyleItalic">Primers</span> n&#227;o descritos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">25 CEC IS<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13 DB IS<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CBC IC&#58; 36 de 96 &#40;37&#44;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">28 CEC IC<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">23 DB IC<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Wieland et al&#46;&#44; 2009&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sim&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CCM&#58; 30 de 34 &#40;88&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&#42;<span class="elsevierStyleItalic">Primers</span> para LT1 e LT3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CCM Mx<span class="elsevierStyleSup">b</span>&#58; 5 de 5 &#40;100&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CBC IC&#58; 3 de 21 &#40;14&#44;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CEC IC&#58; 1 de 6 &#40;16&#44;6&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">DB IC&#58; 1 de 4 &#40;25&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ceratoacantoma IC&#58; 3 de 7 &#40;42&#44;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Pele adjacente ao CQ&#58; 8 de 34 &#40;23&#44;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Garneski et al&#46;&#44; 2009&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sim&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CCM EUA<span class="elsevierStyleSup">c</span>&#58; 11 de 16 &#40;69&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sim&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">&#42;<span class="elsevierStyleItalic">Primers</span> para sT&#8208;Ag e LT&#8208;Ag&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CCM AUS<span class="elsevierStyleSup">d</span>&#58; 5 de 21 &#40;24&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CEC&#58; 2 de 15 &#40;13&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Pele foto&#8208;exposta&#58; 0 de 15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Becker et al&#46;&#44; 2009&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#42;<span class="elsevierStyleItalic">Primers</span> para LT&#8208;Ag&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CCM&#58; 45 de 53 &#40;84&#44;9&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CBC&#58; 3 de 24 &#40;12&#44;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ridd et al&#46;&#44; 2009&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#42;<span class="elsevierStyleItalic">Primers</span> para LT1&#44; LT3 e VP1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CEC&#58; 0 de 85&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">DB&#58; 0 de 28 Ceratoacantoma&#58; 1 de 37 &#40;2&#44;7&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ceratose act&#237;nica&#58; 0 de 6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Reisinger et al&#46;&#44; 2010&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sim&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CCM&#58; 15 de 20 &#40;75&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#42;Anticorpo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CBC<a class="elsevierStyleCrossRef" href="#tblfn0025"><span class="elsevierStyleSup">e</span></a>&#58; 0 de 9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Monoclonal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CEC<a class="elsevierStyleCrossRef" href="#tblfn0025"><span class="elsevierStyleSup">e</span></a>&#58; 0 de 3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mertz et al&#46;&#44; 2010&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sim&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">DB IS&#58; 2 de 20 &#40;10&#37;&#41; e 2 de 21 &#40;9&#44;5&#37;&#41;<span class="elsevierStyleSup">f</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#42;<span class="elsevierStyleItalic">Primers</span> para LT1&#44; LT3 e VP1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">DB IC&#58; 2 de 24 &#40;8&#44;3&#37;&#41;<span class="elsevierStyleSup">f</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Rollison et al&#46;&#44; 2012&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sim&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CEC&#58; 55 de 145 &#40;38&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#42;<span class="elsevierStyleItalic">Primers</span> para LT&#8208;Ag&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mertz et al&#46;&#44; 2013&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sim&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CBC IS&#58; 8 de 17 &#40;47&#44;1&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sim&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CBC IS&#58; 2 de 17 &#40;11&#44;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#42;<span class="elsevierStyleItalic">Primers</span> para LT&#8208;Ag&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CEC IS&#58; 4 de 15 &#40;26&#44;7&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#42;Anticorpo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CEC IS&#58; 1 de 15 &#40;6&#44;7&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CBC IC&#58; 28 de 71 &#40;39&#44;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Monoclonal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CBC IC&#58; 0 de 71&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CEC IC&#58; 17 de 60 &#40;28&#44;3&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CM2B4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CEC IC&#58; 0 de 60&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Pele normal&#58; 10 de 47 &#40;21&#44;3&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Murakami et al&#46;&#44; 2011&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sim&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CBC IC&#58; 0 de 10 &#40;0&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sim&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CEC IC&#58; 2 de 4<span class="elsevierStyleSup">g</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#42;<span class="elsevierStyleItalic">Primers</span> para LT3 e VP1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CEC IC&#58; 4 de 30 &#40;13&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#42;Anticorpo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Monoclonal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CM2B4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Bellott et al&#46;&#44; 2017&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sim&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CBC IC&#58; 23 de 69 &#40;33&#44;3&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#42;<span class="elsevierStyleItalic">Primers</span> para LT3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CEC IC&#58; 2 de 11 &#40;18&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">DB IC&#58; 2 e 4 DB &#40;50&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ceratoacantoma IC&#58; 1 de 1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Neto et al&#46;&#44; 2019&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sim&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CCM&#58; 13 de 13 &#40;100&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#42;<span class="elsevierStyleItalic">Primers</span> para LT&#8208;Ag&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CQ&#58; 4 de 20 &#40;20&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Costa et al&#46;&#44; 2021&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sim&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CCM&#58; 13 de 20 &#40;65&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#42;<span class="elsevierStyleItalic">Primers</span> para LT&#8208;Ag&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CBC&#58; 2 e 20 &#40;10&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CEC&#58; 3 de 20 &#40;15&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Bellott et al&#46;&#44; 2022&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sim&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CBC IC&#58; 34 de 85 &#40;40&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sim&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IHQ T<span class="elsevierStyleSup">h</span>&#58; 18 de 101 &#40;17&#44;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#42;<span class="elsevierStyleItalic">Primers</span> para LT3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CEC IC&#58; 6 de 12 &#40;50&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#42;Anticorpo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IHQ ST<span class="elsevierStyleSup">i</span>&#58; 10 de 101 &#40;9&#44;9&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">DB IC&#58; 2 de 4 &#40;50&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Monoclonal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IHQ SI<span class="elsevierStyleSup">j</span>&#58; 8 de 101 &#40;7&#44;9&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ceratoacantoma&#58; 1 de 2 &#40;50&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CM2B4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab3303773.png"
              ]
            ]
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          "notaPie" => array:2 [
            0 => array:3 [
              "identificador" => "tblfn0005"
              "etiqueta" => "a"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Dados n&#227;o disponibilizados no artigo&#59; <span class="elsevierStyleSup">b</span> Mx<span class="elsevierStyleSup">2</span> &#8211; met&#225;stases&#59; <span class="elsevierStyleSup">c</span> Estados Unidos&#59; <span class="elsevierStyleSup">d</span> Austr&#225;lia&#59;</p>"
            ]
            1 => array:3 [
              "identificador" => "tblfn0025"
              "etiqueta" => "e"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0010">CBC e CEC oriundos de pacientes com CCM com IHQ positiva para MCPyV&#59; <span class="elsevierStyleSup">f</span> Duas coortes realizadas no mesmo estudo&#59; <span class="elsevierStyleSup">g</span> IHQ realizada apenas nos casos positivos na PCR&#59; <span class="elsevierStyleSup">h</span> IHQ&#8208;T&#58; marca&#231;&#227;o total&#44; marcando c&#233;lulas do tumor&#44; c&#233;lulas do infiltrado linfoc&#237;tico peri&#8208;tumoral&#44; e ambos&#59; <span class="elsevierStyleSup">i</span> IHQ&#8208;ST&#58; marcando apenas c&#233;lulas do tumor&#44; em associa&#231;&#227;o ou n&#227;o com c&#233;lulas do infiltrado linfoc&#237;tico peri&#8208;tumoral&#59; <span class="elsevierStyleSup">j</span> IHQ&#8208;SI&#58; marcando apenas c&#233;lulas do infiltrado linfoc&#237;tico peri&#8208;tumoral&#46;</p> <p class="elsevierStyleNotepara" id="npar0015">&#42;Quando os primers foram descritos&#46;</p> <p class="elsevierStyleNotepara" id="npar0020">&#42;&#42;Quando os primers n&#227;o foram descritos&#46;</p>"
            ]
          ]
        ]
        "descripcion" => array:1 [
          "pt" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Principais estudos&#44; em ordem cronol&#243;gica&#44; que investigam a presen&#231;a de part&#237;culas virais do MCPyV em carcinoma de queratin&#243;citos</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "Refer&#234;ncias"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0015"
          "bibliografiaReferencia" => array:74 [
            0 => array:3 [
              "identificador" => "bib0375"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Global burden of cancers attributable to infections in 2008&#58; a review and synthetic analysis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "C&#46; Martel"
                            1 => "J&#46; Ferlay"
                            2 => "S&#46; Franceschi"
                            3 => "J&#46; Vignat"
                            4 => "F&#46; Bray"
                            5 => "D&#46; Forman"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S1470-2045(12)70137-7"
                      "Revista" => array:6 [
                        "tituloSerie" => "Lancet Oncol&#46;"
                        "fecha" => "2012"
                        "volumen" => "13"
                        "paginaInicial" => "607"
                        "paginaFinal" => "615"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22575588"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0380"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Global burden of cancers attributable to infections in 2012&#58; a synthetic analysis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "M&#46; Plummer"
                            1 => "C&#46; Martel"
                            2 => "J&#46; Vignat"
                            3 => "J&#46; Ferlay"
                            4 => "F&#46; Bray"
                            5 => "S&#46; Franceschi"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S2214-109X(16)30143-7"
                      "Revista" => array:6 [
                        "tituloSerie" => "Lancet Glob Health&#46;"
                        "fecha" => "2016"
                        "volumen" => "4"
                        "paginaInicial" => "e609"
                        "paginaFinal" => "e616"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27470177"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0385"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Infection and cancer&#58; global distribution and burden of diseases"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "J&#46;-K&#46; Oh"
                            1 => "E&#46; Weiderpass"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:4 [
                        "tituloSerie" => "Ann Glob Heal&#46;"
                        "fecha" => "2014"
                        "volumen" => "80"
                        "paginaInicial" => "384"
                      ]
                    ]
                  ]
                ]
              ]
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Educação médica continuada
Poliomavírus de células de Merkel e sua relação etiológica com tumores cutâneos
Thiago Rubim Bellotta,
Corresponding author
thiagobellott@id.uff.br

Autor para correspondência.
, Flávio Barbosa Luzb, Anna Karoline Fausto da Silvaa, Rafael Brandão Varellac, Mayra Carrijo Rochaela, Luciana Pantaleãoa
a Departamento de Patologia, Hospital Universitário Antônio Pedro, Universidade Federal Fluminense, Niterói, RJ, Brasil
b Departamento de Dermatologia, Hospital Universitário Antônio Pedro, Universidade Federal Fluminense, Niterói, RJ, Brasil
c Departamento de Microbiologia e Parasitologia, Instituto Biomédico, Universidade Federal Fluminense, Niterói, RJ, Brasil
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v&#237;rus linfotr&#243;pico de c&#233;lulas T humanas &#40;HTLV&#41; e poliomav&#237;rus de c&#233;lulas de Merkel &#40;MCPyV&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0390"><span class="elsevierStyleSup">4&#44;5</span></a> Essa conclus&#227;o &#233; feita com base no conhecimento acumulado de um grande n&#250;mero de estudos experimentais&#44; cl&#237;nicos e epidemiol&#243;gicos das &#250;ltimos cinco d&#233;cadas&#46;<a class="elsevierStyleCrossRefs" href="#bib0375"><span class="elsevierStyleSup">1&#8211;5</span></a> Apesar de muitas viroses animais e humanas poderem transformar c&#233;lulas normais em oncog&#234;nicas&#44; ainda h&#225; poucas viroses consistentemente associadas &#224;s neoplasias nos humanos&#46; Dentre os v&#237;rus que causam infec&#231;&#227;o persistente e que t&#234;m comprovado potencial oncog&#234;nico&#44; destacam&#8208;se os poliomav&#237;rus &#40;PyV&#41;&#44; que s&#227;o&#44; com frequ&#234;ncia&#44; encontrados em les&#245;es neopl&#225;sicas&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">&#201; not&#225;vel&#44; tamb&#233;m&#44; que em virtude da onipresen&#231;a e persist&#234;ncia desses v&#237;rus&#44; sua associa&#231;&#227;o causal com essas neoplasias e outras les&#245;es n&#227;o neopl&#225;sicas variadas &#233; de dif&#237;cil interpreta&#231;&#227;o&#46; Postula&#8208;se que a reativa&#231;&#227;o e cronifica&#231;&#227;o dessas infec&#231;&#245;es possam estar relacionadas ao processo de maligniza&#231;&#227;o em decorr&#234;ncia da inj&#250;ria tecidual cr&#244;nica&#46; Al&#233;m disso&#44; tem sido relatada a presen&#231;a concomitante desses agentes virais em alguns tumores&#44; indicando poss&#237;vel papel coestimulat&#243;rio do processo infeccioso&#46;<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">1</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">A oncog&#234;nese &#233; via multifatorial&#44; e sistemas virais suportam a no&#231;&#227;o de que o desenvolvimento do tumor ocorre pelo ac&#250;mulo de eventos m&#250;ltiplos&#44; enquanto a presen&#231;a do DNA viral nas c&#233;lulas tumorais n&#227;o &#233;&#44; necessariamente&#44; um fator causal&#46; A transforma&#231;&#227;o celular causada pela infec&#231;&#227;o viral pode conduzir &#224; ativa&#231;&#227;o de oncogenes ou &#224; inativa&#231;&#227;o de genes supressores de tumor&#44; tornando&#8208;se mecanismos importantes na oncog&#234;nese viral&#46;<a class="elsevierStyleCrossRefs" href="#bib0400"><span class="elsevierStyleSup">6&#44;7</span></a> A produ&#231;&#227;o de prote&#237;nas oncog&#234;nicas consiste no principal mecanismo oncog&#234;nico de alguns retrov&#237;rus&#44; enquanto a inativa&#231;&#227;o de prote&#237;nas supressoras de tumor ocorre em alguns v&#237;rus de DNA como os PyV&#46; Para esses&#44; a inibi&#231;&#227;o e degrada&#231;&#227;o das prote&#237;nas regulat&#243;rias como a prote&#237;na p53 e a prote&#237;na do retinoblastoma consiste em sua principal estrat&#233;gia&#46;<a class="elsevierStyleCrossRefs" href="#bib0400"><span class="elsevierStyleSup">6&#44;7</span></a> Al&#233;m disso&#44; a inflama&#231;&#227;o cr&#244;nica&#44; muitas vezes causada por outros agentes infecciosos&#44; pode levar ao aumento do risco de c&#226;ncer&#44; como nos casos de c&#226;ncer de c&#243;lon na colite ulcerativa&#46; A compet&#234;ncia do sistema imune tamb&#233;m &#233; fundamental para o controle do processo infeccioso e oncog&#234;nico&#59; a imunossupress&#227;o &#233; um dos principais fatores de risco de progress&#227;o para neoplasias&#46;<a class="elsevierStyleCrossRefs" href="#bib0400"><span class="elsevierStyleSup">6&#44;7</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Desde a descoberta do MCPyV&#44; em 2008&#44;<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">8</span></a> considerado o primeiro PyV humano inequivocamente relacionado &#224; uma neoplasia em humanos&#44; o carcinoma de c&#233;lulas de Merkel &#40;CCM&#41;&#44; uma neoplasia rara&#44; de origem possivelmente neuroend&#243;crina e de curso agressivo&#44; a detec&#231;&#227;o do seu genoma viral come&#231;ou a ser investigada n&#227;o apenas em casos de CCM&#44; mas tamb&#233;m em diversas outras neoplasias cut&#226;neas&#44; denominados de c&#226;ncer de pele n&#227;o melanoma &#40;CPNM&#41; ou carcinoma de queratin&#243;citos &#40;CQ&#41;&#44; como o carcinoma basocelular &#40;CBC&#41; e o carcinoma cut&#226;neo de c&#233;lulas escamosas &#40;CEC&#41;&#44; o que despertou grande interesse de diversos pesquisadores&#46;<a class="elsevierStyleCrossRefs" href="#bib0415"><span class="elsevierStyleSup">9&#8211;13</span></a></p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Hist&#243;ria do poliomav&#237;rus e do poliomav&#237;rus de c&#233;lulas de Merkel</span><p id="par0025" class="elsevierStylePara elsevierViewall">O primeiro PyV foi isolado em 1953 por Ludwik Gross&#44; e recebeu esse nome por ser agente causal de m&#250;ltiplos tumores em roedores &#40;do grego <span class="elsevierStyleItalic">poli</span>&#58; 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Internacional de Taxonomia de V&#237;rus &#40;ICTV&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0440"><span class="elsevierStyleSup">14</span></a> Atualmente&#44; divide&#8208;se a fam&#237;lia Polyomaviridae em seis g&#234;neros e 117 esp&#233;cies com base nas rela&#231;&#245;es filogen&#233;ticas da sequ&#234;ncia de amino&#225;cido do LT&#8208;Ag&#58; <span class="elsevierStyleItalic">Alphapolyomavirus</span>&#44; <span class="elsevierStyleItalic">Betapolyomavirus</span>&#44; <span class="elsevierStyleItalic">Gammapolyomavirus</span>&#44; <span class="elsevierStyleItalic">Deltapolyomavirus</span>&#44; <span class="elsevierStyleItalic">Epsilonpolyomavirus</span> e <span class="elsevierStyleItalic">Zetapolyomavirus</span>&#44; acrescido de um grupamento de esp&#233;cies ainda sem g&#234;nero definido&#46;<a class="elsevierStyleCrossRef" href="#bib0450"><span class="elsevierStyleSup">16</span></a> O g&#234;nero <span class="elsevierStyleItalic">Alphapolyomavirus</span> re&#250;ne esp&#233;cies de PyV que infectam humanos e animais&#44; incluindo os poliomav&#237;rus humanos &#40;HPyV&#41; 5 ou MCPyV&#44; HPyV8 ou poliomav&#237;rus associado a tricodisplasia spinulosa &#40;TSPyV&#41;&#44; HPyV9&#44; HPyV12 e HPyV13&#59; o g&#234;nero <span class="elsevierStyleItalic">Betapolyomavirus</span> conta com esp&#233;cies que infectam humanos e animais&#44; incluindo HPyV1 e HpyV4&#59; o g&#234;nero <span class="elsevierStyleItalic">Deltapolyomavirus</span> cont&#233;m os HPyV6&#44; HPyV7&#44; HPyV10 e HPyV11&#59; o g&#234;nero <span class="elsevierStyleItalic">Gammapolyomavirus</span>&#44; <span class="elsevierStyleItalic">Epsilonpolyomavirus</span> e <span class="elsevierStyleItalic">Zetapolyomavirus</span>&#44; descritos recentemente&#44; re&#250;nem outras esp&#233;cies que infectam mam&#237;feros e peixes&#44; somando&#8208;se ainda as esp&#233;cies de PyVs sem g&#234;nero definido &#40;<a class="elsevierStyleCrossRef" href="#fig0010">fig&#46; 2</a>&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0440"><span class="elsevierStyleSup">14&#44;16&#44;17</span></a></p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">At&#233; 2007&#44; somente duas esp&#233;cies haviam sido descritas como membros da fam&#237;lia que infectavam humanos&#58; o HPyV1 ou poliomav&#237;rus BK &#40;BKPyV&#41;&#44; e o HPyV2 ou John Cunningham poliomav&#237;rus ou V&#237;rus JC &#40;JCPyV&#41;&#46; Dessa data em diante&#44; em virtude da evolu&#231;&#227;o da tecnologia para sequenciamento gen&#233;tico&#44; outros 12 HPyV foram descritos e nomeados conforme a ordem cronol&#243;gica de sua descoberta&#44; totalizando as 14 esp&#233;cies que infectam humanos conhecidas atualmente &#40;<a class="elsevierStyleCrossRef" href="#fig0015">fig&#46; 3</a>&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0450"><span class="elsevierStyleSup">16&#8211;18</span></a></p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0040" class="elsevierStylePara elsevierViewall">Diversas dessas esp&#233;cies t&#234;m afinidade pelo tecido cut&#226;neo&#44; incluindo o HPyV6&#44; HPyV7&#44; HPyV9&#44; TSPyV e o MCPyV&#46;<a class="elsevierStyleCrossRefs" href="#bib0465"><span class="elsevierStyleSup">19&#8211;22</span></a> Sabe&#8208;se que doen&#231;as significantes causadas por PyV ocorrem em pacientes imunossuprimidos&#44; como leucoencefalopatia multifocal progressiva em pacientes com s&#237;ndrome da imunodefici&#234;ncia adquirida pelo JCPyV&#44; cistite hemorr&#225;gica em pacientes ap&#243;s transplante alog&#234;nico de c&#233;lulas&#8208;tronco hematopo&#233;ticas pelo BKPyV&#44; entre outros&#46; Cerca de 10&#37; dos pacientes transplantados renais desenvolvem nefropatia associada ao BKPyV&#44; com perda de fun&#231;&#227;o do enxerto em at&#233; 50&#37; dos casos da doen&#231;a&#46;<a class="elsevierStyleCrossRef" href="#bib0485"><span class="elsevierStyleSup">23</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Classifica&#231;&#227;o criada pela Ag&#234;ncia Internacional de Pesquisa em c&#226;ncer &#40;International Agency for Research on Cancer &#8211; IARC&#41; da Organiza&#231;&#227;o Mundial de Sa&#250;de &#40;OMS&#41; divide os agentes carcinog&#234;nicos em grupos&#44; separados pela sua maior ou menor a&#231;&#227;o carcinog&#234;nica em humanos&#44; baseados em evid&#234;ncia&#58; Grupo 1 como agentes carcinog&#234;nicos em humanos&#59; Grupo 2A como agentes provavelmente carcinog&#234;nicos em humanos&#59; Grupo 2B como agentes possivelmente carcinog&#234;nicos em humanos&#59; Grupo 3 como agentes n&#227;o relacionados &#224; carcinog&#234;nese em humanos&#46; Entre os agentes virais envolvidos ou potencialmente copart&#237;cipes na oncog&#234;nese&#44; encontram&#8208;se os HPyV&#44; notadamente o MCPyV&#46; Com base nessa classifica&#231;&#227;o da OMS&#44; o MCPyV foi classificado como sendo do Grupo 2A&#46;<a class="elsevierStyleCrossRefs" href="#bib0395"><span class="elsevierStyleSup">5&#44;24&#44;25</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">Evid&#234;ncias sorol&#243;gicas suportam a persist&#234;ncia da infec&#231;&#227;o pelos HPyV&#46; Pela medi&#231;&#227;o de anticorpos contra a prote&#237;na VP1 do caps&#237;dio viral&#44; pode&#8208;se inferir que a exposi&#231;&#227;o ao HPyV ocorre na inf&#226;ncia&#44; com aumento da soropreval&#234;ncia ao passar dos anos&#44; medindo&#8208;se n&#237;veis muito baixos at&#233; os 18 meses de vida e pr&#243;ximos dos 80&#37; aos 5 anos de idade&#46;<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">8</span></a> Ensaios sorol&#243;gicos realizados especificamente para o MCPyV tamb&#233;m confirmam essa onipresen&#231;a viral&#44; em que 80&#37; dos adultos apresentavam anticorpos contra o v&#237;rus&#46;<a class="elsevierStyleCrossRef" href="#bib0500"><span class="elsevierStyleSup">26</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">A presen&#231;a do DNA do MCPyV&#44; detectada em cargas virais vari&#225;veis pela t&#233;cnica de PCR&#44; tamb&#233;m tem sido descrita em diversos tecidos n&#227;o tumorais&#44; como na pele&#44; sangue perif&#233;rico&#44; tratos gastrintestinal&#44; respirat&#243;rio e urin&#225;rio&#44; gl&#226;ndula suprarrenal&#44; ba&#231;o&#44; medula &#243;ssea&#44; est&#244;mago&#44; ves&#237;cula biliar&#44; p&#226;ncreas&#44; cora&#231;&#227;o e aorta&#44; embora com &#237;ndice relativamente baixo de carga viral&#44; entre 0&#44;00026 e 0&#44;22 c&#243;pias por c&#233;lula&#46;<a class="elsevierStyleCrossRefs" href="#bib0505"><span class="elsevierStyleSup">27&#8211;30</span></a> Em m&#233;dia&#44; o n&#250;mero de c&#243;pias do genoma viral de MCPyV foi 60 vezes menor em tecidos saud&#225;veis quando comparados com amostras de CCM&#46;<a class="elsevierStyleCrossRef" href="#bib0510"><span class="elsevierStyleSup">28</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">Outro fator que refor&#231;a que a infec&#231;&#227;o pelo MCPyV seja onipresente e assintom&#225;tica &#233; o de que 60&#37; a 80&#37; da popula&#231;&#227;o eliminem continuamente o MCPyV atrav&#233;s da pele saud&#225;vel&#46;<a class="elsevierStyleCrossRef" href="#bib0525"><span class="elsevierStyleSup">31</span></a> Relatos recentes tamb&#233;m reportam que os fibroblastos presentes na derme podem suportar a replica&#231;&#227;o viral e podem ser c&#233;lulas hospedeiras genu&#237;nas para esse v&#237;rus&#46;<a class="elsevierStyleCrossRef" href="#bib0530"><span class="elsevierStyleSup">32</span></a></p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Carcinoma de c&#233;lulas de Merkel e poliomav&#237;rus de c&#233;lulas de Merkel</span><p id="par0065" class="elsevierStylePara elsevierViewall">Apesar de a oncogenicidade do PyV ser largamente relatada na literatura desde 1950&#44; a primeira descri&#231;&#227;o de PyV como agente etiol&#243;gico de neoplasia em humanos foi feita apenas em 2008&#44; com a descri&#231;&#227;o do MCPyV&#44; presente em cerca de 80&#37; dos casos de CCM e agente etiol&#243;gico desse tumor&#46;<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">8</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">O CCM &#233; neoplasia rara&#44; de origem possivelmente neuroend&#243;crina&#44; com curso agressivo&#44; e normalmente acomete pacientes de idade avan&#231;ada&#44; imunossuprimidos&#44; em locais de fotoexposi&#231;&#227;o cr&#244;nica&#46; A les&#227;o costuma se apresentar como p&#225;pula ou n&#243;dulo eritematoso&#44; de crescimento r&#225;pido e sem sintomas associados&#46; A maioria dessas les&#245;es apresenta tr&#234;s ou mais caracter&#237;sticas resumidas no acr&#244;nimo AEIOU&#58; A de &#8220;A<span class="elsevierStyleItalic">symptomatic nodule</span>&#8221; ou n&#243;dulo assintom&#225;tico&#59; E de &#8220;E<span class="elsevierStyleItalic">xpanding rapidly</span>&#8221; ou expans&#227;o r&#225;pida&#59; I de &#8220;I<span class="elsevierStyleItalic">mmunosuppressed host</span>&#8221; ou hospedeiro imunossuprimido&#59; O de &#8220;O<span class="elsevierStyleItalic">lder than age</span> 50&#8221; ou idade acima de 50 anos&#59; e U de &#8220;UV <span class="elsevierStyleItalic">exposed sites</span><span class="elsevierStyleItalic">or fair skin</span>&#8221; ou locais fotoexpostos aos raios ultravioletas &#40;UV&#41; ou pele clara<a class="elsevierStyleCrossRef" href="#bib0535"><span class="elsevierStyleSup">33</span></a> &#40;<a class="elsevierStyleCrossRef" href="#fig0020">fig&#46; 4</a>&#41;&#46;</p><elsevierMultimedia ident="fig0020"></elsevierMultimedia><p id="par0075" class="elsevierStylePara elsevierViewall">Apesar de as c&#233;lulas tumorais compartilharem caracter&#237;sticas morfol&#243;gicas e histol&#243;gicas com as c&#233;lulas de Merkel&#44; h&#225; um debate sobre a origem desse tumor&#46; Isso se deve ao fato de que as c&#233;lulas de Merkel s&#227;o p&#243;s&#8208;mit&#243;ticas&#44; estando em est&#225;gio de diferencia&#231;&#227;o terminal e n&#227;o realizando mitoses&#44; o que dificulta bastante a origem de um tumor&#46; Outro questionamento &#233; que o CCM raramente acomete os locais onde h&#225; c&#233;lulas de Merkel&#44; como palmas&#44; plantas&#44; leito ungueal e mucosa oral e genital&#46; Somam&#8208;se a esse fato a aus&#234;ncia de descri&#231;&#227;o de les&#245;es displ&#225;sicas ou precursoras desse tumor&#44; a localiza&#231;&#227;o das c&#233;lulas de Merkel na epiderme&#44; enquanto o CCM se localiza na derme&#44; a diferen&#231;a de fen&#243;tipos entre a c&#233;lula de Merkel e o CCM&#46; Desse modo&#44; postula&#8208;se que outras c&#233;lulas possam ser respons&#225;veis pela origem desse tumor&#44; e os poss&#237;veis candidatos incluem c&#233;lulas&#8208;tronco epid&#233;rmicas&#44; queratin&#243;citos &#40;as c&#233;lulas predominantes em todas as camadas de c&#233;lulas epid&#233;rmicas&#41;&#44; fibroblastos d&#233;rmicos&#44; c&#233;lulas pr&#243;&#8208;B ou c&#233;lulas pr&#233;&#8208;B &#40;<a class="elsevierStyleCrossRef" href="#fig0025">fig&#46; 5</a>&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0390"><span class="elsevierStyleSup">4&#44;33&#44;34</span></a></p><elsevierMultimedia ident="fig0025"></elsevierMultimedia><p id="par0080" class="elsevierStylePara elsevierViewall">Nessa rara neoplasia cut&#226;nea&#44; o DNA viral se integra clonalmente ao DNA da c&#233;lula hospedeira pelo resultado de muta&#231;&#227;o&#46; O padr&#227;o de integra&#231;&#227;o clonal do DNA do MCPyV ao DNA da c&#233;lula hospedeira sugere que a infe&#231;&#227;o viral ocorreu anteriormente &#224; expans&#227;o clonal das c&#233;lulas neopl&#225;sicas do CCM&#46;<a class="elsevierStyleCrossRef" href="#bib0445"><span class="elsevierStyleSup">15</span></a> Em adi&#231;&#227;o a essa muta&#231;&#227;o que causou a integra&#231;&#227;o clonal&#44; uma segunda muta&#231;&#227;o &#233; necess&#225;ria para o desenvolvimento dessa neoplasia&#44; o que justifica em parte a raridade dessa entidade&#46; A segunda muta&#231;&#227;o pode ser induzida pela exposi&#231;&#227;o aos raios UV e &#233; representada pela truncagem do LT&#8208;Ag do MCPyV&#46; Essa muta&#231;&#227;o&#44; em &#250;ltima an&#225;lise&#44; levar&#225; a uma inibi&#231;&#227;o da prote&#237;na supressora de tumor RB nessas c&#233;lulas infectadas&#44; acarretando no aumento dos fatores de transcri&#231;&#227;o E2F e desencadeamento da fase S do ciclo celular&#44; de maneira semelhante ao que ocorre no mecanismo de oncog&#234;nese pela oncoprote&#237;na E7 do HPV&#46; O LT&#8208;Ag tamb&#233;m contribui para a oncog&#234;nese por meio do est&#237;mulo &#224; angiog&#234;nese e &#224; atividade da telomerase&#44; al&#233;m da inibi&#231;&#227;o de vias intracelulares que levam &#224; apoptose&#46; O sT&#8208;Ag tamb&#233;m parece ter m&#250;ltiplas fun&#231;&#245;es oncog&#234;nicas e agiria em conjunto com o LT&#8208;Ag para a conclus&#227;o desse processo&#46;<a class="elsevierStyleCrossRef" href="#bib0545"><span class="elsevierStyleSup">35</span></a> Feng et al&#46;<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">8</span></a> descrevem a integra&#231;&#227;o do genoma do MCPyV ao genoma celular anteriormente &#224; expans&#227;o clonal das c&#233;lulas neopl&#225;sicas&#44; al&#233;m dessas muta&#231;&#245;es tumor&#8208;espec&#237;ficas de truncagem do LT&#8208;Ag&#46;<a class="elsevierStyleCrossRefs" href="#bib0410"><span class="elsevierStyleSup">8&#44;36</span></a> Tais muta&#231;&#245;es t&#234;m sido relatadas tamb&#233;m em uma parcela de leucemia linfoc&#237;tica cr&#244;nica<a class="elsevierStyleCrossRef" href="#bib0555"><span class="elsevierStyleSup">37</span></a> e c&#226;ncer de pulm&#227;o de c&#233;lulas n&#227;o pequenas&#46;<a class="elsevierStyleCrossRef" href="#bib0560"><span class="elsevierStyleSup">38</span></a> O genoma viral tamb&#233;m foi encontrado em c&#226;ncer de c&#233;lulas escamosas e adenocarcinomas cervicais<a class="elsevierStyleCrossRef" href="#bib0565"><span class="elsevierStyleSup">39</span></a> e leucemias linfoides&#44;<a class="elsevierStyleCrossRefs" href="#bib0570"><span class="elsevierStyleSup">40&#44;41</span></a> embora n&#227;o exista ainda comprova&#231;&#227;o etiol&#243;gica do MCPyV em malignidades diferentes de CCM&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">Estudos recentes t&#234;m dado maior relev&#226;ncia ao papel oncog&#234;nico do sT&#8208;Ag do que se pensava anteriormente&#46; Uma diferen&#231;a fundamental entre o MCPyV e outros PyV &#233; que o sT&#8208;Ag parece estar diretamente envolvido na transforma&#231;&#227;o neopl&#225;sica induzida por MCPyV no CCM&#46;<a class="elsevierStyleCrossRef" href="#bib0580"><span class="elsevierStyleSup">42</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">Liu et al&#46;&#44;<a class="elsevierStyleCrossRefs" href="#bib0530"><span class="elsevierStyleSup">32&#44;42</span></a> depois de examinar queratin&#243;citos epid&#233;rmicos&#44; fibroblastos d&#233;rmicos&#44; c&#233;lulas de Merkel e muitos outros tipos de c&#233;lulas na pele&#44; descobriram que apenas os fibroblastos d&#233;rmicos s&#227;o permissivos &#224; entrada&#44; transcri&#231;&#227;o e replica&#231;&#227;o do MCPyV&#46;<a class="elsevierStyleCrossRefs" href="#bib0530"><span class="elsevierStyleSup">32&#44;42</span></a> Esses fibroblastos&#44; quando tratados com fator de crescimento epid&#233;rmico e fator de crescimento b&#225;sico de fibroblastos&#44; foram particularmente eficazes no suporte &#224; infec&#231;&#227;o pelo MCPyV&#44; e como esses fatores de crescimento costumam ser tipicamente regulados positivamente em locais de feridas cut&#226;neas&#44; sugere&#8208;se que o processo de cicatriza&#231;&#227;o possa induzir um microambiente tecidual prop&#237;cio &#224; infec&#231;&#227;o e replica&#231;&#227;o do MCPyV&#46;<a class="elsevierStyleCrossRefs" href="#bib0530"><span class="elsevierStyleSup">32&#44;42</span></a></p><p id="par0095" class="elsevierStylePara elsevierViewall">Tem sido sugerido&#44; em estudos inicialmente realizados na popula&#231;&#227;o australiana&#44; que a participa&#231;&#227;o do MCPyV na g&#234;nese do CCM seja pouco frequente em tumores localizados em &#225;reas fotodanificadas de indiv&#237;duos de pele clara&#46;<a class="elsevierStyleCrossRef" href="#bib0585"><span class="elsevierStyleSup">43</span></a> Essa informa&#231;&#227;o &#233; corroborada pela menor frequ&#234;ncia de detec&#231;&#227;o do DNA viral em casos de CCM associados &#224; diferencia&#231;&#227;o escamosa&#44; que costuma ocorrer apenas em &#225;reas fotodanificadas&#44; levando &#224; hip&#243;tese de que haja uma via alternativa de oncog&#234;nese nesses tumores independente do v&#237;rus&#46;<a class="elsevierStyleCrossRefs" href="#bib0590"><span class="elsevierStyleSup">44&#44;45</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">A taxa de positividade viral vista em tumores de regi&#245;es com e sem fotoexposi&#231;&#227;o tamb&#233;m foi estudada por Dabner et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0600"><span class="elsevierStyleSup">46</span></a> utilizando&#8208;se como par&#226;metros histol&#243;gicos a elastose solar na derme e a displasia epid&#233;rmica como sinais de dano act&#237;nico cr&#244;nico&#46; Os resultados demonstram o mesmo padr&#227;o&#44; com menor presen&#231;a viral em tumores de &#225;reas fotoexpostas&#46; Em conson&#226;ncia&#44; Paik et al&#46;<a class="elsevierStyleCrossRef" href="#bib0595"><span class="elsevierStyleSup">45</span></a> tamb&#233;m demonstraram menor positividade do MCPyV em CCM por imuno&#8208;histoqu&#237;mica em indiv&#237;duos australianos&#44; com taxa de detec&#231;&#227;o de 7&#44;7&#37; &#40;3 em 39&#41; nos tumores localizados na cabe&#231;a e pesco&#231;o e de 24&#44;6&#37; &#40;16 em 65&#41; em outras localiza&#231;&#245;es do corpo&#46; Esses estudos refor&#231;am a possibilidade de que os tumores localizados em regi&#245;es fotoexpostas&#44; como cabe&#231;a e pesco&#231;o&#44; tenham outras vias de carcinog&#234;nese n&#227;o relacionadas &#224; presen&#231;a viral&#44; o que explicaria a baixa detec&#231;&#227;o por esse m&#233;todo nesses tumores&#46;<a class="elsevierStyleCrossRef" href="#bib0595"><span class="elsevierStyleSup">45</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">No entanto&#44; h&#225; estudos que apontam na dire&#231;&#227;o contr&#225;ria&#44; demonstrando maior presen&#231;a do DNA viral&#44; por meio da t&#233;cnica de PCR&#44; em CPNM de locais fotoexpostos&#46; Esse resultado levanta a hip&#243;tese de que a carcinog&#234;nese viral age como fator complementar &#224; carcinog&#234;nse induzida pela radia&#231;&#227;o UV&#46;<a class="elsevierStyleCrossRef" href="#bib0605"><span class="elsevierStyleSup">47</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">At&#233; o presente momento&#44; ainda n&#227;o existe um teste padr&#227;o&#8208;ouro para a detec&#231;&#227;o do MCPyV&#44; e mesmo a utiliza&#231;&#227;o combinada de PCR e imuno&#8208;histoqu&#237;mica &#40;IHQ&#41; tem resultados sub&#243;timos&#46;<a class="elsevierStyleCrossRef" href="#bib0610"><span class="elsevierStyleSup">48</span></a> Estudos anteriores que utilizaram as duas t&#233;cnicas combinadas para a detec&#231;&#227;o do MCPyV em CCM tiveram maior positividade com a t&#233;cnica de PCR&#44; o que sugere sua maior sensibilidade&#46;<a class="elsevierStyleCrossRefs" href="#bib0590"><span class="elsevierStyleSup">44&#44;49&#8211;52</span></a> No entanto&#44; outros autores descreveram a detec&#231;&#227;o do MCPyV em CCM com t&#233;cnicas combinadas em que houve maior detec&#231;&#227;o viral por meio da IHQ &#8211; os autores atribu&#237;ram esse achado &#224; grande diversidade de metodologias na t&#233;cnica de PCR para o MCPyV&#44; como utiliza&#231;&#227;o de <span class="elsevierStyleItalic">primer</span> com diferentes sequ&#234;ncias gen&#233;ticas&#44; n&#250;mero de conjuntos de <span class="elsevierStyleItalic">primers</span> do v&#237;rus detectado&#44; diferen&#231;as na sequ&#234;ncia humana de refer&#234;ncia que &#233; amplificada e os limites de corte usados para considerar um teste positivo&#46; &#201; poss&#237;vel que o ensaio de PCR mais sens&#237;vel e espec&#237;fico para detec&#231;&#227;o de MCPyV ainda n&#227;o tenha sido comparado com os ensaios de IHC&#46;<a class="elsevierStyleCrossRef" href="#bib0610"><span class="elsevierStyleSup">48</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">C&#226;ncer de pele n&#227;o melanoma e carcinoma de queratin&#243;citos relacionados ao poliomav&#237;rus de c&#233;lulas de Merkel</span><p id="par0115" class="elsevierStylePara elsevierViewall">O c&#226;ncer de pele n&#227;o melanoma &#40;CPNM&#41; ou CQ engloba basicamente todas as malignidades cut&#226;neas que n&#227;o se referem ao melanoma&#46; No entanto&#44; grande parte desses tumores correspondem ao carcinoma basocelular &#40;CBC&#41;&#44; ao carcinoma cut&#226;neo de c&#233;lulas escamosas ou carcinoma espinocelular &#40;CEC&#41; e suas variantes&#46;<a class="elsevierStyleCrossRef" href="#bib0635"><span class="elsevierStyleSup">53</span></a> O CQ n&#227;o inclui outros tipos de malignidades cut&#226;neas mais raras e com comportamentos distintos&#44; como o pr&#243;prio CCM&#44; o dermatofibrossarcoma&#44; linfomas cut&#226;neos&#44; carcinomas seb&#225;ceos&#44; angiossarcomas e outros tumores dos anexos cut&#226;neos&#46;<a class="elsevierStyleCrossRef" href="#bib0640"><span class="elsevierStyleSup">54</span></a></p><p id="par0120" class="elsevierStylePara elsevierViewall">Considerando o papel do MCPyV no desenvolvimento do CCM e sua detec&#231;&#227;o em diversos outros tecidos e tumores do corpo humano&#44; alguns pesquisadores come&#231;aram a investigar um poss&#237;vel papel etiol&#243;gico desse v&#237;rus na g&#234;nese de outros tumores&#44; majoritariamente em CQ&#46;<a class="elsevierStyleCrossRef" href="#bib0645"><span class="elsevierStyleSup">55</span></a> Na maioria desses estudos&#44;<a class="elsevierStyleCrossRefs" href="#bib0415"><span class="elsevierStyleSup">9&#8211;13</span></a> o DNA do MCPyV foi detectado pela t&#233;cnica de PCR&#44; havendo&#44; no entanto&#44; alguns estudos em que o LT&#8208;Ag tamb&#233;m foi investigado pela t&#233;cnica de IHQ&#44; demonstrando na maioria das vezes uma positividade menor do que na t&#233;cnica de PCR&#46;<a class="elsevierStyleCrossRef" href="#bib0645"><span class="elsevierStyleSup">55</span></a></p><p id="par0125" class="elsevierStylePara elsevierViewall">Kassem et al&#46;<a class="elsevierStyleCrossRef" href="#bib0420"><span class="elsevierStyleSup">10</span></a> demonstraram a presen&#231;a do MCPyV pela t&#233;cnica de PCR em 36 de 96 &#40;37&#44;5&#37;&#41; CBC acometendo pacientes imunocompetentes&#46; Em rela&#231;&#227;o aos CBC de pacientes imunossuprimidos&#44; os valores foram surpreendentemente altos&#44; positivos em 72&#44;2&#37; dos casos&#46; Os mesmos autores descrevem a presen&#231;a de MCPyV em 7 de 28 casos &#40;25&#37;&#41; de CEC em pacientes imunocompetentes&#46; Semelhante ao que ocorreu com os CBC&#44; o percentual subiu para 52&#37; em pacientes imunossuprimidos&#46; Tamb&#233;m foi descrita alta positividade na doen&#231;a de Bowen &#40;DB&#41;&#44; com 17&#44;4&#37; de positividade entre pacientes imunocompetentes e 69&#37; entre pacientes imunossuprimidos&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">Ainda em 2009&#44; Dworkin et al&#46;<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">9</span></a> descreveram positividade do MCPyV em 26 de 177 &#40;15&#37;&#41; CEC oriundos de pacientes imunocompetentes&#46;<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">9</span></a> Al&#233;m da positividade nos CEC&#44; tamb&#233;m se descreveu positividade de 17&#37; na pele adjacente ao tumor &#40;11 de 63 amostras&#41;&#46; Houve&#44; entre os casos pareados &#40;tumor e pele adjacente ao tumor&#41;&#44; uma concord&#226;ncia &#40;presen&#231;a ou aus&#234;ncia do DNA viral em ambos os esp&#233;cimes&#41; de 87&#37;&#46; Esse achado sugere que&#44; apesar da aus&#234;ncia de altera&#231;&#245;es histol&#243;gicas espec&#237;ficas&#44; o v&#237;rus j&#225; poderia estar presente na &#225;rea perilesional&#44; levando ao futuro desenvolvimento da les&#227;o tumoral&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">Zur Hausen et al&#46;<a class="elsevierStyleCrossRef" href="#bib0650"><span class="elsevierStyleSup">56</span></a> examinaram um total de 56 CQ oriundos de 11 pacientes imunossuprimidos &#40;25 CEC&#44; 13 DB e 18 CBC&#41; e 147 tumores oriundos de 125 pacientes imunocompetentes &#40;28 CEC&#44; 23 doen&#231;as de Bowen e 96 CBC&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0650"><span class="elsevierStyleSup">56</span></a> Houve detec&#231;&#227;o significantemente mais frequente de positividade para MCPyV nos tumores cut&#226;neos de pacientes imunossuprimidos nos tr&#234;s tipos de tumor&#44; com signific&#226;ncia estat&#237;stica &#40;p &#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#46; Todos os produtos de PCR tamb&#233;m foram sequenciados nesse estudo&#59; as muta&#231;&#245;es espec&#237;ficas do tumor na &#225;rea do LT&#8208;Ag n&#227;o puderam ser detectadas&#46; A carga viral tamb&#233;m foi analisada&#44; e na grande maioria dos CQ&#44; a carga viral do MCPyV estava bem abaixo dos casos de CCM positivos para MCPyV usados como controles&#46;<a class="elsevierStyleCrossRef" href="#bib0650"><span class="elsevierStyleSup">56</span></a></p><p id="par0140" class="elsevierStylePara elsevierViewall">Wieland et al&#46;<a class="elsevierStyleCrossRef" href="#bib0655"><span class="elsevierStyleSup">57</span></a> analisaram a presen&#231;a do MCPyV pela t&#233;cnica de PCR em 355 amostras de pele&#44; incluindo uma grande gama de CQ&#44; melanomas&#44; les&#245;es benignas e pele sadia perilesional&#46;<a class="elsevierStyleCrossRef" href="#bib0655"><span class="elsevierStyleSup">57</span></a> Houve positividade para a presen&#231;a viral em tr&#234;s dos 21 CBC &#40;14&#37;&#41;&#44; um de seis CEC &#40;17&#37;&#41;&#44; um de quatro doen&#231;as de Bowen &#40;25&#37;&#41;&#44; tr&#234;s de sete ceratoacantomas &#40;43&#37;&#41;&#44; dois de 12 melanomas &#40;17&#37;&#41;&#44; nenhum caso positivo em verrugas virais e ceratoses act&#237;nicas&#44; e oito de 34 casos de detec&#231;&#227;o em pele sadia perilesional &#40;24&#37;&#41;&#46; O DNA viral foi encontrado em 30 dos 34 casos de CCM utilizados como controle&#44; e com carga viral maior do que a encontrada nos CQ&#44; resultado similar ao descrito por Zur Hausen et al&#46;<a class="elsevierStyleCrossRefs" href="#bib0650"><span class="elsevierStyleSup">56&#44;57</span></a></p><p id="par0145" class="elsevierStylePara elsevierViewall">Garneski et al&#46;<a class="elsevierStyleCrossRef" href="#bib0585"><span class="elsevierStyleSup">43</span></a> encontraram uma taxa de 13&#37; de positividade do MCPyV em CEC&#44; em que duas das 15 les&#245;es de CEC estudadas albergavam o DNA viral&#46;<a class="elsevierStyleCrossRef" href="#bib0585"><span class="elsevierStyleSup">43</span></a> Em contrapartida&#44; Reisinger et al&#46;<a class="elsevierStyleCrossRef" href="#bib0660"><span class="elsevierStyleSup">58</span></a> pesquisaram a positividade do LT&#8208;Ag por IHQ&#44; utilizando o anticorpo CM2B4 em 20 pacientes com CCM e em alguns CBC e CEC oriundos desses mesmos pacientes&#46; Um total de 12 desses pacientes apresentavam CBC e CEC que se desenvolveram ap&#243;s a detec&#231;&#227;o do CCM&#59; a pesquisa do LT&#8208;Ag por IHQ utilizando o anticorpo monoclonal CM2B4 veio negativa em todos os 12 casos&#46; De maneira oposta&#44; esses pacientes tinham alta positividade de 92&#37; &#40;11 em 12&#41; para o LT&#8208;Ag visto por IHQ em seus CCM&#46;<a class="elsevierStyleCrossRef" href="#bib0660"><span class="elsevierStyleSup">58</span></a> Rollison et al&#46;<a class="elsevierStyleCrossRef" href="#bib0665"><span class="elsevierStyleSup">59</span></a> descreveram um percentual de 38&#37; de positividade do MCPyV DNA em amostras de tecido congelado fresco de CEC obtidos de pacientes imunocompetentes&#46; A presen&#231;a do MCPyV DNA se associou a altos n&#237;veis de anticorpos anti&#8208;MCPyV circulantes&#46;<a class="elsevierStyleCrossRef" href="#bib0665"><span class="elsevierStyleSup">59</span></a> Esse expressivo percentual em pacientes imunocompetentes pode ser decorrente do fato de as amostras terem sido estudadas imediatamente ap&#243;s sua retirada e n&#227;o ap&#243;s processamento do material em blocos de parafina&#44; evitando a poss&#237;vel degrada&#231;&#227;o parcial do material gen&#233;tico presente&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">Em conson&#226;ncia com esses estudos&#44; Mertz et al&#46;<a class="elsevierStyleCrossRef" href="#bib0670"><span class="elsevierStyleSup">60</span></a> detectaram o DNA do MCPyV por PCR em dois &#40;10&#37;&#41; de 20 pacientes com DB&#46; Em um desses pacientes&#44; que era imunossuprimido por transplante renal&#44; foram tamb&#233;m avaliadas diversas outras les&#245;es cut&#226;neas&#44; com positividade para o MCPyV em quatro de quatro verrugas virais &#40;100&#37;&#41;&#44; tr&#234;s de seis doen&#231;as de Bowen &#40;50&#37;&#41;&#44; e duas de tr&#234;s ceratoses seborreicas &#40;66&#44;6&#37;&#41;&#46; Em uma segunda coorte realizada em pacientes imunossuprimidos e submetidos a transplante renal&#44; o DNA do MCPyV foi encontrado em uma de 16 verrugas virais &#40;6&#44;3&#37;&#41;&#44; em duas de 21 Doen&#231;as de Bowen &#40;9&#44;5&#37;&#41;&#46; Em indiv&#237;duos imunocompetentes&#44; o DNA do MCPyV foi encontrado em duas das 30 verrugas virais &#40;6&#44;7&#37;&#41; e em duas das 24 Doen&#231;as de Bowen &#40;8&#44;3&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0670"><span class="elsevierStyleSup">60</span></a></p><p id="par0155" class="elsevierStylePara elsevierViewall">Os mesmos pesquisadores&#44;<a class="elsevierStyleCrossRef" href="#bib0435"><span class="elsevierStyleSup">13</span></a> em 2013&#44; encontraram positividade para o v&#237;rus em 28 de 71 &#40;39&#44;4&#37;&#41; CBC retirados de pacientes imunocompetentes&#46; Essa taxa subiu para 47&#44;1&#37; em imunossuprimidos&#44; em que oito de 17 CBC albergavam o DNA viral&#46; Em contraste com a frequente detec&#231;&#227;o viral por PCR nese estudo&#44; a IHQ para a pesquisa do LT&#8208;Ag no tecido tumoral foi positiva apenas em dois dos 17 casos de CBC que acometiam pacientes imunossuprimidos&#44; e negativa em todos CBC dos pacientes imunocompetentes&#46;<a class="elsevierStyleCrossRef" href="#bib0435"><span class="elsevierStyleSup">13</span></a> Nesse mesmo ano&#44; Murakami et al&#46;<a class="elsevierStyleCrossRef" href="#bib0675"><span class="elsevierStyleSup">61</span></a> encontraram quatro de 30 &#40;13&#37;&#41; CEC positivos para MCPyV&#59; desses quatro&#44; dois tamb&#233;m eram positivos para LT&#8208;Ag pela IHQ&#46; Tamb&#233;m foi descrito no mesmo estudo uma total negatividade para a presen&#231;a do MCPyV pela PCR em 10 casos de CBC&#44; n&#227;o obstante o fato do pequeno n&#250;mero total de casos dificultar a an&#225;lise&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">Becker et al&#46;&#44; ap&#243;s confirmarem a presen&#231;a do MCPyV em 45 de 53 &#40;84&#44;9&#37;&#41; pacientes com CCM&#44; descreveram positividade viral em tr&#234;s de 24 &#40;12&#44;5&#37;&#41; casos de CBC&#46;<a class="elsevierStyleCrossRef" href="#bib0680"><span class="elsevierStyleSup">62</span></a></p><p id="par0165" class="elsevierStylePara elsevierViewall">Neto et al&#46;<a class="elsevierStyleCrossRef" href="#bib0680"><span class="elsevierStyleSup">62</span></a> tamb&#233;m fizeram an&#225;lise recente entre a presen&#231;a de MCPyV e tumores cut&#226;neos&#44; analisando 10 casos de CBC e 10 de CEC&#46; Pela t&#233;cnica de PCR com extra&#231;&#227;o do material gen&#233;tico de material guardado em bloco de parafina&#44; foi detectado material gen&#233;tico do MCPyV em quatro dos 20 casos&#44; em compara&#231;&#227;o com a presen&#231;a em 100&#37; dos 20 casos de CCM analisados tamb&#233;m nesse estudo&#46;<a class="elsevierStyleCrossRef" href="#bib0685"><span class="elsevierStyleSup">63</span></a></p><p id="par0170" class="elsevierStylePara elsevierViewall">Ridd et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0685"><span class="elsevierStyleSup">63</span></a> ap&#243;s investigarem a presen&#231;a do DNA do MCPyV por PCR em 85 casos de CEC&#44; 37 ceratoacantomas&#44; 28 doen&#231;as de Bowen e seis ceratoses act&#237;nicas&#44; encontraram positividade apenas em um caso de ceratoacantoma&#46; A t&#233;cnica de PCR desse estudo foi validada em uma coorte de CCM&#44; que demonstrou 54&#37; &#40;7&#47;13&#41; dos tumores positivos para a presen&#231;a do MCPyV&#46;<a class="elsevierStyleCrossRef" href="#bib0690"><span class="elsevierStyleSup">64</span></a></p><p id="par0175" class="elsevierStylePara elsevierViewall">Kaibuchi&#8208;Noda et al&#46;<a class="elsevierStyleCrossRef" href="#bib0695"><span class="elsevierStyleSup">65</span></a> descreveram um relato de caso em que um paciente imunossuprimido&#44; um ano ap&#243;s ter CEC ressecado&#44; apresentou met&#225;stases diagnosticadas como CCM&#44; tendo realizado a pesquisa do DNA do MCPyV por PCR e do LT&#8208;Ag por IHQ&#46;<a class="elsevierStyleCrossRef" href="#bib0695"><span class="elsevierStyleSup">65</span></a> O estudo revelou que o DNA do MCPyV foi detectado na les&#227;o de CEC&#44; indicando que a infec&#231;&#227;o pelo MCPyV ocorrera pelo menos um ano antes da ocorr&#234;ncia de CCM metast&#225;tico&#46; No entanto&#44; o n&#250;mero de c&#243;pias do MCPyV por c&#233;lula na les&#227;o de CCM foi maior que na de CEC&#44; e a pesquisa do LT&#8208;Ag pela IHQ foi positiva apenas no CCM&#44; colocando em d&#250;vida se houve participa&#231;&#227;o efetiva do MCPyV na g&#234;nese de ambos os tumores ou se apenas no CCM&#46;<a class="elsevierStyleCrossRef" href="#bib0695"><span class="elsevierStyleSup">65</span></a></p><p id="par0180" class="elsevierStylePara elsevierViewall">Estudos recentes tamb&#233;m indicam a presen&#231;a de outros HPyV em ceratoacantomas e outros CQ&#46; Beckervordersandforth et al&#46;<a class="elsevierStyleCrossRef" href="#bib0700"><span class="elsevierStyleSup">66</span></a> descreveram a presen&#231;a do HPyV6 por PCR em diversos tumores inclu&#237;dos no grupo de CPNM&#59; 25 dos 59 &#40;42&#44;3&#37;&#41; dos ceratoacantomas apresentavam material gen&#233;tico&#44; assim como 23 dos 109 &#40;21&#44;1&#37;&#41; casos de CBC e oito dos 86 &#40;9&#44;3&#37;&#41; casos de CCE&#46;<a class="elsevierStyleCrossRef" href="#bib0700"><span class="elsevierStyleSup">66</span></a></p><p id="par0185" class="elsevierStylePara elsevierViewall">A presen&#231;a do HPyV6&#44; assim como a de outros HPyV&#44; como o MCPyV&#44; TSPyV&#44; HPyV6&#44; HPyV7&#44; HPyV9 e HPyV10&#44; tamb&#233;m foi investigada em CEC de pacientes com melanoma em tratamento com inibidores de BRAF&#46;<a class="elsevierStyleCrossRef" href="#bib0705"><span class="elsevierStyleSup">67</span></a> At&#233; o momento&#44; os &#250;nicos fatores identificados que contribuem para o desenvolvimento de CEC nesses pacientes s&#227;o muta&#231;&#245;es nos genes <span class="elsevierStyleItalic">RAS</span>&#46; No entanto&#44; essas muta&#231;&#245;es explicam apenas 60&#37; dos tumores&#46; &#201; importante identificar o que est&#225; causando os tumores remanescentes&#46; Dezoito amostras de biopsia de seis pacientes foram avaliadas&#44; 10 &#40;62&#37;&#41; das 16 amostras continham muta&#231;&#245;es RAS&#59; o DNA de HPyV9&#44; HPyV10 e TSPyV estava ausente nas amostras&#44; o DNA do MCPyV estava presente em 13 das 18 amostras &#40;72&#44;22&#37;&#41;&#59; e o DNA do HPV&#44; HPyV6 e HPyV7 estava presente em todas as amostras&#46; Em geral&#44; a carga viral encontrada nesse estudo foi baixa&#44; com exce&#231;&#227;o do HPyV6&#44; que tamb&#233;m foi detectado por IHQ com os ant&#237;genos da prote&#237;na central VP1&#46;<a class="elsevierStyleCrossRef" href="#bib0705"><span class="elsevierStyleSup">67</span></a> Haeggblom et al&#46; descreveram a presen&#231;a de PyV em ceratoacantomas e nevos de Spitz e&#44; apesar de n&#227;o haver predomin&#226;ncia de nenhuma esp&#233;cie espec&#237;fica&#44; foi encontrado material gen&#233;tico viral pela t&#233;cnica de PCR em 20 de 47 les&#245;es dessas afec&#231;&#245;es&#46;<a class="elsevierStyleCrossRef" href="#bib0710"><span class="elsevierStyleSup">68</span></a></p><p id="par0190" class="elsevierStylePara elsevierViewall">Estudo realizado por Toptan et al&#46;<a class="elsevierStyleCrossRef" href="#bib0715"><span class="elsevierStyleSup">69</span></a> investigou&#44; por meio de um anticorpo utilizado na t&#233;cnica de IHQ que detecta simultaneamente uma ampla gama de HPyV&#44; incluindo o MCPyV&#44; a presen&#231;a desse v&#237;rus em centenas de tumores&#44; dentre eles o CBC e o CEC&#46; N&#227;o foi detectada presen&#231;a do MCPyV nesses carcinomas cut&#226;neos&#44; e raras c&#233;lulas marcadas com esse anticorpo em alguns tumores espor&#225;dicos foi interpretado como infec&#231;&#227;o passageira e incidental&#46;<a class="elsevierStyleCrossRef" href="#bib0715"><span class="elsevierStyleSup">69</span></a></p><p id="par0195" class="elsevierStylePara elsevierViewall">Estudando 96 les&#245;es cut&#226;neas&#44; Bellott et al&#46;<a class="elsevierStyleCrossRef" href="#bib0430"><span class="elsevierStyleSup">12</span></a> detectaram a presen&#231;a do MCPyV em 31&#37; desses casos&#44; dos quais 23 &#40;33&#44;3&#37;&#41; dentre os 69 casos de CBC&#44; dois dos 11 CEC &#40;18&#37;&#41;&#44; duas das quatro doen&#231;as de Bowen &#40;50&#37;&#41; e&#44; dentre as outras 11 les&#245;es cut&#226;neas&#44; quatro &#40;36&#44;3&#37;&#41; foram positivos para o DNA viral &#40;duas ceratoses act&#237;nicas&#44; um dermatofibrosarcoma e um ceratoacantoma&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0430"><span class="elsevierStyleSup">12</span></a> Estudo mais recente pelo mesmo autor&#44;<a class="elsevierStyleCrossRef" href="#bib0720"><span class="elsevierStyleSup">70</span></a> dessa vez analisando a presen&#231;a do genoma viral do MCPyV pela t&#233;cnica de PCR e do LT&#8208;Ag maior pela t&#233;cnica de IHQ&#44; teve 103 amostras de CQ de 91 pacientes analisadas&#46; Quarenta e quatro &#40;42&#44;7&#37;&#41; tumores foram positivos para o v&#237;rus via PCR&#44; 34 de 85 &#40;40&#37;&#41; no grupo CBC&#44; seis de 12 &#40;50&#37;&#41; no CEC&#44; dois de quatro &#40;50&#37;&#41; para DB e um de dois &#40;50&#37;&#41; para ceratoacantoma&#46; O resultado da IHQ mostra positividade total em 18 casos &#40;17&#44;7&#37;&#41;&#44; sete casos de positividade apenas no tumor &#40;6&#44;9&#37;&#41;&#44; oito no infiltrado peritumoral &#40;7&#44;9&#37;&#41; e tr&#234;s em ambos &#40;3&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0720"><span class="elsevierStyleSup">70</span></a></p><p id="par0200" class="elsevierStylePara elsevierViewall">Costa et al&#46;<a class="elsevierStyleCrossRef" href="#bib0725"><span class="elsevierStyleSup">71</span></a> tamb&#233;m realizaram a pesquisa de diversos HPyV por meio da t&#233;cnica de PCR em tecidos cut&#226;neos&#44; incluindo casos de CQ&#44; melanoma&#44; sarcoma de Kaposi&#44; CCM e pele normal&#46; O MCPyV foi o HPyV mais encontrado&#44; presente em dois de 20 &#40;10&#37;&#41; CBC e tr&#234;s de 20 &#40;15&#37;&#41; CEC&#44; al&#233;m de n&#227;o estar presente em um total de 20 casos de pele normal&#46;<a class="elsevierStyleCrossRef" href="#bib0725"><span class="elsevierStyleSup">71</span></a></p><p id="par0205" class="elsevierStylePara elsevierViewall">Os principais estudos que investigaram a presen&#231;a de part&#237;culas virais do MCPyV em CQ se encontram reunidos em ordem cronol&#243;gica na <a class="elsevierStyleCrossRef" href="#tbl0005">tabela 1</a>&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Discuss&#227;o</span><p id="par0210" class="elsevierStylePara elsevierViewall">Existem muitas suposi&#231;&#245;es para a varia&#231;&#227;o da preval&#234;ncia do MCPyV nos CQ entre diferentes estudos e as diverg&#234;ncias desses resultados com os de IHQ&#46;</p><p id="par0215" class="elsevierStylePara elsevierViewall">A detec&#231;&#227;o do DNA do MCPyV pela t&#233;cnica de PCR pode ser afetada pelos <span class="elsevierStyleItalic">primers</span> que foram usados&#46; De fato&#44; a maioria dos estudos aplicou os <span class="elsevierStyleItalic">primers</span> LT&#8208;Ag originalmente usados por Feng et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">8</span></a> considerados superiores aos <span class="elsevierStyleItalic">primers</span> direcionados contra a VP1&#46;<a class="elsevierStyleCrossRef" href="#bib0645"><span class="elsevierStyleSup">55</span></a></p><p id="par0220" class="elsevierStylePara elsevierViewall">A qualidade das amostras tamb&#233;m pode afetar o resultado da rea&#231;&#227;o de PCR&#44; pois v&#225;rios estudos relataram que a detec&#231;&#227;o do DNA do MCPyV em tecidos frescos congelados &#233; mais confi&#225;vel quando em compara&#231;&#227;o com a detec&#231;&#227;o em amostras fixadas na parafina&#46;<a class="elsevierStyleCrossRef" href="#bib0645"><span class="elsevierStyleSup">55</span></a></p><p id="par0225" class="elsevierStylePara elsevierViewall">O DNA viral &#233; extra&#237;do de um fragmento do tumor&#44; tendo acesso a somente um subgrupo das c&#233;lulas presentes na neoplasia&#46; H&#225; a possibilidade de que haja part&#237;culas virais presentes em locais do tumor que n&#227;o tenham sido analisados em conjunto pela PCR e pela IHQ&#46; O tumor &#233; composto por diversas linhagens celulares heterog&#234;neas que cont&#234;m c&#233;lulas tumorais&#44; infiltrados celulares imunes como de linf&#243;citos&#44; c&#233;lulas endoteliais e fibroblastos associados ao c&#226;ncer&#46; Sabendo que os fibroblastos podem suportar a replica&#231;&#227;o viral e podem ser c&#233;lulas hospedeiras genu&#237;nas para esse v&#237;rus&#44;<a class="elsevierStyleCrossRef" href="#bib0530"><span class="elsevierStyleSup">32</span></a> e tamb&#233;m que os mon&#243;citos infiltrados podem ser reservat&#243;rios para o v&#237;rus&#44;<a class="elsevierStyleCrossRef" href="#bib0730"><span class="elsevierStyleSup">72</span></a> produtos de PCR positivos podem derivar de infec&#231;&#227;o viral nessas c&#233;lulas&#46;</p><p id="par0230" class="elsevierStylePara elsevierViewall">M&#233;todos baseados em PCR tamb&#233;m s&#227;o propensos &#224; contamina&#231;&#227;o&#44; j&#225; que se postula que o MCPyV seja eliminado cronicamente pela pele&#44; podendo fazer parte de sua microbiota&#59;<a class="elsevierStyleCrossRef" href="#bib0735"><span class="elsevierStyleSup">73</span></a> a contamina&#231;&#227;o durante a coleta no manuseio das amostras n&#227;o pode ser exclu&#237;da&#46;</p><p id="par0235" class="elsevierStylePara elsevierViewall">A detec&#231;&#227;o simult&#226;nea do LT&#8208;Ag pela IHQ e do seu material gen&#233;tico por PCR nesses tecidos tumorais pode demonstrar evid&#234;ncias de uma participa&#231;&#227;o ativa do v&#237;rus na manuten&#231;&#227;o do crescimento cancer&#237;geno&#44; e todos esses estudos demonstram que&#44; para ajudar a elucidar se o MCPyV est&#225; realmente associado &#224; g&#234;nese dos CQ&#44; mais estudos epidemiol&#243;gicos ainda s&#227;o necess&#225;rios&#46;<a class="elsevierStyleCrossRef" href="#bib0735"><span class="elsevierStyleSup">73</span></a></p><p id="par0240" class="elsevierStylePara elsevierViewall">Outras etapas que s&#227;o ainda importantes para a elucida&#231;&#227;o dessa quest&#227;o entre o poss&#237;vel papel etiol&#243;gico do MCPyV em tumores outros que n&#227;o o CCM&#44; s&#227;o&#58;</p><p id="par0245" class="elsevierStylePara elsevierViewall">O estado do genoma do v&#237;rus deve ser determinado&#44; se episomal ou integrado&#44; j&#225; que a integra&#231;&#227;o do genoma viral parece ser um pr&#233;&#8208;requisito para o desenvolvimento do processo neopl&#225;sico associado a esse v&#237;rus&#59;<a class="elsevierStyleCrossRef" href="#bib0645"><span class="elsevierStyleSup">55</span></a></p><p id="par0250" class="elsevierStylePara elsevierViewall">O gene que codifica o LT&#8208;Ag deve ser sequenciado para determinar se h&#225; a express&#227;o das muta&#231;&#245;es tumor&#8208;espec&#237;ficas de do LT&#8208;Ag truncado&#59;<a class="elsevierStyleCrossRef" href="#bib0645"><span class="elsevierStyleSup">55</span></a></p><p id="par0255" class="elsevierStylePara elsevierViewall">Hibridiza&#231;&#227;o <span class="elsevierStyleItalic">in situ</span> para o DNA ou RNA viral deve ser feita para garantir que as sequ&#234;ncias virais sejam detectadas em c&#233;lulas tumorais e n&#227;o em outros tipos de c&#233;lulas adjacentes ao tumor&#46;<a class="elsevierStyleCrossRef" href="#bib0645"><span class="elsevierStyleSup">55</span></a></p><p id="par0260" class="elsevierStylePara elsevierViewall">Amostras de tumor em diferentes est&#225;dios de desenvolvimento tamb&#233;m devem ser examinadas&#44; j&#225; que o v&#237;rus pode estar envolvido apenas no in&#237;cio do processo neopl&#225;sico&#44; n&#227;o sendo necess&#225;rio para a progress&#227;o do tumor&#46;<a class="elsevierStyleCrossRef" href="#bib0645"><span class="elsevierStyleSup">55</span></a> De fato&#44; um mecanismo de ataque e fuga para a a&#231;&#227;o oncog&#234;nica do MCPyV em alguns casos de CCM foi sugerido por Houben et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0740"><span class="elsevierStyleSup">74</span></a> no qual a oncog&#234;nese viral s&#243; seria essencial para desencadear o in&#237;cio do processo&#46;<a class="elsevierStyleCrossRef" href="#bib0740"><span class="elsevierStyleSup">74</span></a></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Conclus&#227;o</span><p id="par0265" class="elsevierStylePara elsevierViewall">Diversas informa&#231;&#245;es&#44; como a alta soropreval&#234;ncia de MCPyV na popula&#231;&#227;o humana&#44; os potenciais oncog&#234;nicos <span class="elsevierStyleItalic">in vitro</span> do LT&#8208;Ag e do sT&#8208;Ag e seu papel etiol&#243;gico no CCM&#44; sugerem que o MCPyV pode desempenhar um papel&#44; de maneira isolada ou em associa&#231;&#227;o com outros fatores&#44; em outros tipos de c&#226;ncer no homem&#44; especialmente em indiv&#237;duos com sistema imunol&#243;gico comprometido&#59; entretanto&#44; essa rela&#231;&#227;o causal entre o MCPyV e CQ ainda n&#227;o pode ser estabelecida&#46;<a class="elsevierStyleCrossRef" href="#bib0645"><span class="elsevierStyleSup">55</span></a></p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Suporte financeiro</span><p id="par0270" class="elsevierStylePara elsevierViewall">O presente estudo faz parte da tese de doutorado do autor principal e foi contemplado com bolsa de pesquisa do FUNADERM &#40;Fundo de Apoio &#224; Dermatologia&#41;&#44; &#243;rg&#227;o da Sociedade Brasileira de Dermatologia&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Contribui&#231;&#227;o dos autores</span><p id="par0275" class="elsevierStylePara elsevierViewall">Thiago Rubim Bellott&#58; Concep&#231;&#227;o e o desenho do estudo&#59; levantamento dos dados&#44; ou an&#225;lise e interpreta&#231;&#227;o dos dados&#59; reda&#231;&#227;o do artigo ou revis&#227;o cr&#237;tica do conte&#250;do intelectual importante&#59; obten&#231;&#227;o&#44; an&#225;lise e interpreta&#231;&#227;o dos dados&#59; participa&#231;&#227;o efetiva na orienta&#231;&#227;o da pesquisa&#59; participa&#231;&#227;o intelectual em conduta proped&#234;utica e&#47;ou terap&#234;utica de casos estudados&#59; revis&#227;o cr&#237;tica da literatura&#59; aprova&#231;&#227;o final da vers&#227;o final do manuscrito&#46;</p><p id="par0280" class="elsevierStylePara elsevierViewall">Fl&#225;vio Barbosa Luz&#58; Concep&#231;&#227;o e o desenho do estudo&#59; reda&#231;&#227;o do artigo ou revis&#227;o cr&#237;tica do conte&#250;do intelectual importante&#59; obten&#231;&#227;o&#44; an&#225;lise e interpreta&#231;&#227;o dos dados&#59; participa&#231;&#227;o efetiva na orienta&#231;&#227;o da pesquisa&#59; participa&#231;&#227;o intelectual em conduta proped&#234;utica e&#47;ou terap&#234;utica de casos estudados&#59; aprova&#231;&#227;o final da vers&#227;o final do manuscrito&#46;</p><p id="par0285" class="elsevierStylePara elsevierViewall">Anna Karolinne Fausto&#58; Participa&#231;&#227;o efetiva na orienta&#231;&#227;o da pesquisa&#59; participa&#231;&#227;o intelectual em conduta proped&#234;utica e&#47;ou terap&#234;utica de casos estudados&#59; aprova&#231;&#227;o final da vers&#227;o final do manuscrito&#46;</p><p id="par0290" class="elsevierStylePara elsevierViewall">Rafael Brand&#227;o Varella&#58; Participa&#231;&#227;o efetiva na orienta&#231;&#227;o da pesquisa&#59; participa&#231;&#227;o intelectual em conduta proped&#234;utica e&#47;ou terap&#234;utica de casos estudados&#59; aprova&#231;&#227;o final da vers&#227;o final do manuscrito&#46;</p><p id="par0295" class="elsevierStylePara elsevierViewall">Mayra Carrijo Rochael&#59; Participa&#231;&#227;o efetiva na orienta&#231;&#227;o da pesquisa&#59; participa&#231;&#227;o intelectual em conduta proped&#234;utica e&#47;ou terap&#234;utica de casos estudados&#59; aprova&#231;&#227;o final da vers&#227;o final do manuscrito&#46;</p><p id="par0300" class="elsevierStylePara elsevierViewall">Luciana Pantale&#227;o&#58; Participa&#231;&#227;o efetiva na orienta&#231;&#227;o da pesquisa&#59; participa&#231;&#227;o intelectual em conduta proped&#234;utica e&#47;ou terap&#234;utica de casos estudados&#59; aprova&#231;&#227;o final da vers&#227;o final do manuscrito&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Conflito de interesses</span><p id="par0305" class="elsevierStylePara elsevierViewall">Nenhum&#46;</p></span></span>"
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          "titulo" => "C&#226;ncer de pele n&#227;o melanoma e carcinoma de queratin&#243;citos relacionados ao poliomav&#237;rus de c&#233;lulas de Merkel"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">V&#237;rus t&#234;m sido frequentemente identificados em diversas neoplasias humanas&#44; embora seu papel etiol&#243;gico em alguns tumores ainda seja motivo de controv&#233;rsia&#46; Os principais v&#237;rus com capacidade oncog&#234;nica s&#227;o os poliomav&#237;rus&#44; especificamente o poliomav&#237;rus de c&#233;lulas de Merkel &#40;MCPyV&#41;&#46; Revis&#245;es recentes na taxonomia dos poliomav&#237;rus dividiram a fam&#237;lia Polyomaviridae em seis g&#234;neros&#44; incluindo 117 esp&#233;cies&#44; com um total de 14 esp&#233;cies que infectam humanos atualmente conhecidas&#46; Apesar de a oncogenicidade do poliomav&#237;rus ser largamente relatada na literatura desde 1950&#44; a primeira descri&#231;&#227;o de poliomav&#237;rus como agente etiol&#243;gico de neoplasia em humanos foi feita apenas em 2008&#44; com a descri&#231;&#227;o do MCPyV&#44; presente em cerca de 80&#37; dos casos de carcinoma de c&#233;lulas Merkel &#40;CCM&#41;&#44; com a integra&#231;&#227;o de seu genoma ao das c&#233;lulas tumorais e muta&#231;&#245;es tumor&#8208;espec&#237;ficas&#44; sendo considerado o agente etiol&#243;gico dessa neoplasia desde ent&#227;o&#46; O MCPyV tamb&#233;m j&#225; foi detectado em carcinomas de queratin&#243;citos&#44; como o carcinoma basocelular e o carcinoma de c&#233;lulas escamosas da pele em indiv&#237;duos com e sem imunossupress&#227;o&#46; Dados sobre a ocorr&#234;ncia de viroses oncog&#234;nicas e potencialmente envolvidas na oncog&#234;nese&#44; que causam persist&#234;ncia e inj&#250;ria tecidual&#44; relacionados ao poliomav&#237;rus de c&#233;lulas de Merkel ainda s&#227;o escassos&#44; permanecendo em aberto a hip&#243;tese de que o poliomav&#237;rus de c&#233;lulas de Merkel possa ter papel relevante na g&#234;nese de outros carcinomas cut&#226;neos al&#233;m do CCM&#46; Portanto&#44; o artigo se prop&#245;e ao aprofundamento no estado atual de conhecimento sobre a presen&#231;a do MCPyV em carcinomas de queratin&#243;citos&#46;</p></span>"
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          "pt" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Genoma do MCPyV&#58; regi&#227;o controle n&#227;o codificante &#40;NCCR&#44; <span class="elsevierStyleItalic">non coding control region</span>&#41;&#59; regi&#227;o de codifica&#231;&#227;o inicial <span class="elsevierStyleItalic">&#40;early region&#41;&#44;</span> que codifica os ant&#237;geno&#8208;T maior &#40;LT&#8208;Ag&#41; e T&#8208;small &#40;sT&#8208;Ag&#41;&#59; e regi&#227;o de codifica&#231;&#227;o tardia <span class="elsevierStyleItalic">&#40;late region&#41;&#46;</span> LT&#8208;Ag&#44; <span class="elsevierStyleItalic">Large T&#8208;antigen</span> ou ant&#237;geno&#8208;T maior&#59; sT&#8208;Ag&#44; s<span class="elsevierStyleItalic">mall&#8208;T antigen</span> ou ant&#237;geno&#8208;T menor&#59; RCNC&#44; regi&#227;o controle n&#227;o codificante ou <span class="elsevierStyleItalic">non&#8208;coding control region</span>&#59; VP1 e VP2&#44; prote&#237;na do caps&#237;dio viral 1 e 2&#46; Fonte&#58; reproduzida de Liu W et al&#46;&#44; 2016&#46;<a class="elsevierStyleCrossRef" href="#bib0445"><span class="elsevierStyleSup">15</span></a></p>"
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          "leyenda" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">IS&#44; imunossuprimido&#59; IC&#44; imunocompetente&#59;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Autores&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Tecidos investigados&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">PCR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Resultado&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">IHQ&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Resultado&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Kassem et al&#46;&#44; 2009</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CBC&#44; CEC&#44; DB</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sim&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CBC IS&#58; 13 de 18 &#40;72&#44;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#42;<span class="elsevierStyleItalic">Primers</span> para LT3 e VP1</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CEC IS&#58; 13 de 25 &#40;52&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">DB IS&#58; 9 de 13 &#40;69&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CBC IC&#58; 36 de 96 &#40;37&#44;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CEC IC&#58; 7 de 28 &#40;25&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">DB IC&#58; 4 de 23 &#40;17&#44;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dworkin et al&#46;&#44; 2009&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CEC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sim&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CEC IC&#58; 26 de 177 &#40;15&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#42;<span class="elsevierStyleItalic">Primers</span> para LT3 e VP1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Pele adjacente ao CEC&#58; 11 de 63 &#40;17&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Zur Hausen et al&#46;&#44; 2009&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sim&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">18 CBC IS<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#42;&#42;<span class="elsevierStyleItalic">Primers</span> n&#227;o descritos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">25 CEC IS<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13 DB IS<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CBC IC&#58; 36 de 96 &#40;37&#44;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">28 CEC IC<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">23 DB IC<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Wieland et al&#46;&#44; 2009&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sim&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CCM&#58; 30 de 34 &#40;88&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#42;<span class="elsevierStyleItalic">Primers</span> para LT1 e LT3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CCM Mx<span class="elsevierStyleSup">b</span>&#58; 5 de 5 &#40;100&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CBC IC&#58; 3 de 21 &#40;14&#44;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CEC IC&#58; 1 de 6 &#40;16&#44;6&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">DB IC&#58; 1 de 4 &#40;25&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ceratoacantoma IC&#58; 3 de 7 &#40;42&#44;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Pele adjacente ao CQ&#58; 8 de 34 &#40;23&#44;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Garneski et al&#46;&#44; 2009&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sim&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CCM EUA<span class="elsevierStyleSup">c</span>&#58; 11 de 16 &#40;69&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sim&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&#42;<span class="elsevierStyleItalic">Primers</span> para sT&#8208;Ag e LT&#8208;Ag&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CCM AUS<span class="elsevierStyleSup">d</span>&#58; 5 de 21 &#40;24&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CEC&#58; 2 de 15 &#40;13&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Pele foto&#8208;exposta&#58; 0 de 15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Becker et al&#46;&#44; 2009&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#42;<span class="elsevierStyleItalic">Primers</span> para LT&#8208;Ag&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CCM&#58; 45 de 53 &#40;84&#44;9&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CBC&#58; 3 de 24 &#40;12&#44;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ridd et al&#46;&#44; 2009&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#42;<span class="elsevierStyleItalic">Primers</span> para LT1&#44; LT3 e VP1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CEC&#58; 0 de 85&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">DB&#58; 0 de 28 Ceratoacantoma&#58; 1 de 37 &#40;2&#44;7&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ceratose act&#237;nica&#58; 0 de 6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Reisinger et al&#46;&#44; 2010&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sim&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CCM&#58; 15 de 20 &#40;75&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#42;Anticorpo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CBC<a class="elsevierStyleCrossRef" href="#tblfn0025"><span class="elsevierStyleSup">e</span></a>&#58; 0 de 9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Monoclonal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CEC<a class="elsevierStyleCrossRef" href="#tblfn0025"><span class="elsevierStyleSup">e</span></a>&#58; 0 de 3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mertz et al&#46;&#44; 2010&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sim&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">DB IS&#58; 2 de 20 &#40;10&#37;&#41; e 2 de 21 &#40;9&#44;5&#37;&#41;<span class="elsevierStyleSup">f</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#42;<span class="elsevierStyleItalic">Primers</span> para LT1&#44; LT3 e VP1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">DB IC&#58; 2 de 24 &#40;8&#44;3&#37;&#41;<span class="elsevierStyleSup">f</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Rollison et al&#46;&#44; 2012&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sim&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CEC&#58; 55 de 145 &#40;38&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#42;<span class="elsevierStyleItalic">Primers</span> para LT&#8208;Ag&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mertz et al&#46;&#44; 2013&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sim&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CBC IS&#58; 8 de 17 &#40;47&#44;1&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sim&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CBC IS&#58; 2 de 17 &#40;11&#44;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#42;<span class="elsevierStyleItalic">Primers</span> para LT&#8208;Ag&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CEC IS&#58; 4 de 15 &#40;26&#44;7&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#42;Anticorpo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CEC IS&#58; 1 de 15 &#40;6&#44;7&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CBC IC&#58; 28 de 71 &#40;39&#44;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Monoclonal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CBC IC&#58; 0 de 71&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CEC IC&#58; 17 de 60 &#40;28&#44;3&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CM2B4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CEC IC&#58; 0 de 60&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Pele normal&#58; 10 de 47 &#40;21&#44;3&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Murakami et al&#46;&#44; 2011&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sim&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CBC IC&#58; 0 de 10 &#40;0&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sim&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CEC IC&#58; 2 de 4<span class="elsevierStyleSup">g</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#42;<span class="elsevierStyleItalic">Primers</span> para LT3 e VP1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CEC IC&#58; 4 de 30 &#40;13&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#42;Anticorpo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Monoclonal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CM2B4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Bellott et al&#46;&#44; 2017&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sim&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CBC IC&#58; 23 de 69 &#40;33&#44;3&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#42;<span class="elsevierStyleItalic">Primers</span> para LT3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CEC IC&#58; 2 de 11 &#40;18&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">DB IC&#58; 2 e 4 DB &#40;50&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ceratoacantoma IC&#58; 1 de 1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Neto et al&#46;&#44; 2019&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sim&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CCM&#58; 13 de 13 &#40;100&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#42;<span class="elsevierStyleItalic">Primers</span> para LT&#8208;Ag&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CQ&#58; 4 de 20 &#40;20&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Costa et al&#46;&#44; 2021&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sim&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CCM&#58; 13 de 20 &#40;65&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#42;<span class="elsevierStyleItalic">Primers</span> para LT&#8208;Ag&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CBC&#58; 2 e 20 &#40;10&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CEC&#58; 3 de 20 &#40;15&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Bellott et al&#46;&#44; 2022&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sim&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CBC IC&#58; 34 de 85 &#40;40&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sim&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IHQ T<span class="elsevierStyleSup">h</span>&#58; 18 de 101 &#40;17&#44;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#42;<span class="elsevierStyleItalic">Primers</span> para LT3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CEC IC&#58; 6 de 12 &#40;50&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#42;Anticorpo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IHQ ST<span class="elsevierStyleSup">i</span>&#58; 10 de 101 &#40;9&#44;9&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">DB IC&#58; 2 de 4 &#40;50&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Monoclonal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IHQ SI<span class="elsevierStyleSup">j</span>&#58; 8 de 101 &#40;7&#44;9&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ceratoacantoma&#58; 1 de 2 &#40;50&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CM2B4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab3303773.png"
              ]
            ]
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          "notaPie" => array:2 [
            0 => array:3 [
              "identificador" => "tblfn0005"
              "etiqueta" => "a"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Dados n&#227;o disponibilizados no artigo&#59; <span class="elsevierStyleSup">b</span> Mx<span class="elsevierStyleSup">2</span> &#8211; met&#225;stases&#59; <span class="elsevierStyleSup">c</span> Estados Unidos&#59; <span class="elsevierStyleSup">d</span> Austr&#225;lia&#59;</p>"
            ]
            1 => array:3 [
              "identificador" => "tblfn0025"
              "etiqueta" => "e"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0010">CBC e CEC oriundos de pacientes com CCM com IHQ positiva para MCPyV&#59; <span class="elsevierStyleSup">f</span> Duas coortes realizadas no mesmo estudo&#59; <span class="elsevierStyleSup">g</span> IHQ realizada apenas nos casos positivos na PCR&#59; <span class="elsevierStyleSup">h</span> IHQ&#8208;T&#58; marca&#231;&#227;o total&#44; marcando c&#233;lulas do tumor&#44; c&#233;lulas do infiltrado linfoc&#237;tico peri&#8208;tumoral&#44; e ambos&#59; <span class="elsevierStyleSup">i</span> IHQ&#8208;ST&#58; marcando apenas c&#233;lulas do tumor&#44; em associa&#231;&#227;o ou n&#227;o com c&#233;lulas do infiltrado linfoc&#237;tico peri&#8208;tumoral&#59; <span class="elsevierStyleSup">j</span> IHQ&#8208;SI&#58; marcando apenas c&#233;lulas do infiltrado linfoc&#237;tico peri&#8208;tumoral&#46;</p> <p class="elsevierStyleNotepara" id="npar0015">&#42;Quando os primers foram descritos&#46;</p> <p class="elsevierStyleNotepara" id="npar0020">&#42;&#42;Quando os primers n&#227;o foram descritos&#46;</p>"
            ]
          ]
        ]
        "descripcion" => array:1 [
          "pt" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Principais estudos&#44; em ordem cronol&#243;gica&#44; que investigam a presen&#231;a de part&#237;culas virais do MCPyV em carcinoma de queratin&#243;citos</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "Refer&#234;ncias"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0015"
          "bibliografiaReferencia" => array:74 [
            0 => array:3 [
              "identificador" => "bib0375"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Global burden of cancers attributable to infections in 2008&#58; a review and synthetic analysis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "C&#46; Martel"
                            1 => "J&#46; Ferlay"
                            2 => "S&#46; Franceschi"
                            3 => "J&#46; Vignat"
                            4 => "F&#46; Bray"
                            5 => "D&#46; Forman"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S1470-2045(12)70137-7"
                      "Revista" => array:6 [
                        "tituloSerie" => "Lancet Oncol&#46;"
                        "fecha" => "2012"
                        "volumen" => "13"
                        "paginaInicial" => "607"
                        "paginaFinal" => "615"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22575588"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0380"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Global burden of cancers attributable to infections in 2012&#58; a synthetic analysis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "M&#46; Plummer"
                            1 => "C&#46; Martel"
                            2 => "J&#46; Vignat"
                            3 => "J&#46; Ferlay"
                            4 => "F&#46; Bray"
                            5 => "S&#46; Franceschi"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S2214-109X(16)30143-7"
                      "Revista" => array:6 [
                        "tituloSerie" => "Lancet Glob Health&#46;"
                        "fecha" => "2016"
                        "volumen" => "4"
                        "paginaInicial" => "e609"
                        "paginaFinal" => "e616"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27470177"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0385"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Infection and cancer&#58; global distribution and burden of diseases"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "J&#46;-K&#46; Oh"
                            1 => "E&#46; Weiderpass"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:4 [
                        "tituloSerie" => "Ann Glob Heal&#46;"
                        "fecha" => "2014"
                        "volumen" => "80"
                        "paginaInicial" => "384"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0390"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Human oncoviruses&#58; mucocutaneous manifestations&#44; pathogenesis&#44; therapeutics&#44; and prevention&#58; papillomaviruses and Merkel cell polyomavirus"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "C&#46;T&#46; Haley"
                            1 => "U&#46;N&#46; Mui"
                            2 => "R&#46; Vangipuram"
                            3 => "P&#46;L&#46; Rady"
                            4 => "S&#46;K&#46; Tyring"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jaad.2018.09.062"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Am Acad Dermatol&#46;"
                        "fecha" => "2019"
                        "volumen" => "81"
                        "paginaInicial" => "1"
                        "paginaFinal" => "21"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30502418"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib0395"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "monographs&#46;iarc &#91;Internet&#93;&#46; France&#46; World Health Organization&#46; International Agency for Research on Cancer&#46; IARC Monographs on the Evaluation of Carcinogenic Risks to Humans&#46; Volume 90 Human Papillomaviruses&#46; 2007&#46; &#91;Citado em 09 abr&#46; 2023&#93;&#46; Dispon&#237;vel em&#58; &#60;<a target="_blank" href="https://monographs.iarc.who.int/wp-content/uploads/2018/06/mono90.pdf">https&#58;&#47;&#47;monographs&#46;iarc&#46;who&#46;int&#47;wp&#8208;content&#47;uploads&#47;2018&#47;06&#47;mono90&#46;pdf</a>&#62;&#46;"
                ]
              ]
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Article information
ISSN: 26662752
Original language: Portuguese
DOI:10.1016/j.abdp.2023.04.013
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