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as mesmas quest&#245;es podem ser apresentadas em decorr&#234;ncia de seu tropismo epitelial e express&#227;o de prote&#237;nas potencialmente oncog&#234;nicas &#40;ant&#237;genos T&#41;&#46; Dado o tropismo observado de MCPyV e HPyV6 para c&#233;lulas epiteliais&#44; a natureza multifatorial da tumorig&#234;nese e a conhecida associa&#231;&#227;o com doen&#231;as cut&#226;neas correlacionadas&#44; objetivou&#8208;se investigar o DNA desses poliomav&#237;rus humanos com o intuito de elucidar seu poss&#237;vel envolvimento em processos neopl&#225;sicos&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Expandindo um relato anterior&#44; no qual o grupo dos autores observou a presen&#231;a de MCPyV no CBC por meio de abordagem qualitativa&#44; com 25&#44;7&#37; de positividade viral&#44;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">4</span></a> aqui objetivou&#8208;se avaliar e quantificar sua presen&#231;a em v&#225;rias les&#245;es cut&#226;neas malignas e n&#227;o malignas em um popula&#231;&#227;o brasileira&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">M&#233;todo</span><p id="par0020" class="elsevierStylePara elsevierViewall">Foram coletadas 181 amostras congeladas de les&#227;o&#44; pele perilesional e pele normal provenientes de 87 pacientes atendidos no Hospital Universit&#225;rio Ant&#244;nio Pedro &#40;HUAP&#8208;UFF&#41;&#44; entre setembro de 2017 e dezembro de 2018&#46; Dados sobre idade&#44; sexo&#44; estado imunol&#243;gico&#44; etnia e localiza&#231;&#227;o do tumor foram coletados durante a entrevista com o m&#233;dico examinador&#46; A etnia&#44; classificada como &#8216;branca&#8217; ou &#8216;n&#227;o branca&#8217;&#44; foi definida pelo dermatologista de acordo com o fototipo do paciente&#44; enquanto a localiza&#231;&#227;o do tumor foi usada para inferir a exposi&#231;&#227;o solar &#40;alta&#44; moderada ou baixa&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">5</span></a> O diagn&#243;stico histopatol&#243;gico de todas as les&#245;es foi realizado pelo Departamento de Patologia do HUAP&#8208;UFF&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Em rela&#231;&#227;o &#224; amostragem&#44; as bi&#243;psias das les&#245;es consistiram em bi&#243;psias por <span class="elsevierStyleItalic">shaving</span> das les&#245;es&#44; bi&#243;psias da pele perilesional removida pela equipe cir&#250;rgica para garantir a remo&#231;&#227;o completa do tumor&#44; posteriormente confirmada como &#8220;livre de les&#227;o&#8221; por histopatologia&#44; e amostras de pele normal foram obtidas no procedimento para fechar a incis&#227;o cir&#250;rgica&#46; Todas as amostras foram fragmentadas e digeridas com proteinase K &#40;Promega&#174; &#8211; Madison&#44; EUA&#41;&#44; e o DNA foi extra&#237;do utilizando&#8208;se kit comercial de acordo com as instru&#231;&#245;es do fabricante &#40;RTP&#174; DNA&#47;RNA Kit &#8211; Molecular Stratec Biomedical &#8211; Berlim&#44; Alemanha&#41;&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">O DNA de MCPyV e HPyV6 foi quantificado por ensaios TaqMan&#174; qPCR com base em protocolos descritos anteriormente&#46;<a class="elsevierStyleCrossRefs" href="#bib0105"><span class="elsevierStyleSup">6&#44;7</span></a> O gene beta&#8208;globina tamb&#233;m foi amplificado via qPCR para inferir a porcentagem de c&#233;lulas infectadas &#40;DNAviralgenebeta&#8722;globina&#47;2&#41;&#46; A an&#225;lise estat&#237;stica foi realizada com o <span class="elsevierStyleItalic">software</span> SPSS v&#46; 20 &#40;SPSS Inc&#46; &#8211; Chicago&#44; IL&#44; Estados Unidos&#41;&#46; O consentimento informado por escrito foi obtido de todos os indiv&#237;duos que concordaram em participar&#46; Este estudo foi aprovado pelo Comit&#234; de &#201;tica da Universidade&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Resultados</span><p id="par0035" class="elsevierStylePara elsevierViewall">As caracter&#237;sticas demogr&#225;ficas e cl&#237;nicas dos 87 pacientes com CPNM est&#227;o resumidas na <a class="elsevierStyleCrossRef" href="#tbl0005">tabela 1</a>&#46; No geral&#44; a maioria foi classificada como sendo de etnia branca &#40;80&#44;5&#37;&#41;&#44; do sexo feminino &#40;55&#44;2&#37;&#41;&#44; acima de 65 anos &#40;58&#44;1&#37;&#41; e teve o CPNM diagnosticado em &#225;reas com alta exposi&#231;&#227;o ao sol &#40;70&#44;2&#37;&#41;&#59; o carcinoma basocelular &#40;CBC&#41; foi o tipo histopatol&#243;gico mais frequente &#40;60&#44;9&#37;&#41;&#46; As frequ&#234;ncias virais de acordo com idade&#44; sexo e etnia n&#227;o foram significativas&#46; Outras les&#245;es encontradas&#44; classificadas como pr&#233;&#8208;malignas&#44; inclu&#237;ram elastose solar&#44; ceratoacantoma&#44; doen&#231;a de Bowen e hidradenite&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0040" class="elsevierStylePara elsevierViewall">A detec&#231;&#227;o de MCPyV foi elevada no total de bi&#243;psias estudadas &#40;40&#44;2&#37;&#41; em compara&#231;&#227;o com HPyV6 &#40;9&#44;6&#37;&#41;&#46; Embora a detec&#231;&#227;o tenha sido estatisticamente semelhante por tipo de les&#227;o &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">tabela 2</a>&#41;&#44; o MCPyV foi mais frequente em amostras neopl&#225;sicas e pr&#233;&#8208;malignas em conjunto do que em amostras n&#227;o malignas &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;047&#41;&#46; As cargas de MCPyV e porcentagem de c&#233;lulas infectadas n&#227;o foram associadas ao tipo de les&#227;o&#44; tipo de amostra e exposi&#231;&#227;o solar&#46; Curiosamente&#44; a porcentagem de c&#233;lulas infectadas com HPyV6 foi maior &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;012&#41; em amostras de &#225;reas com baixa exposi&#231;&#227;o solar e pele normal&#44; embora a amostragem baixa exija cautela&#46; As cargas de MCPyV foram maiores no subtipo CEC do que no CBC &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;016&#41;&#44; mas n&#227;o em porcentagem de c&#233;lulas infectadas &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;721&#59; dados n&#227;o mostrados&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0045" class="elsevierStylePara elsevierViewall">A concord&#226;ncia da detec&#231;&#227;o de MCPyV entre les&#227;o e pele perilesional foi razo&#225;vel &#40;kappa<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;301&#41;&#44; indicando dissemina&#231;&#227;o viral modesta ao redor da les&#227;o &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">tabela 3</a>&#41;&#46; A baixa taxa de detec&#231;&#227;o de HPyV6 tornou esta an&#225;lise inconclusiva&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Discuss&#227;o</span><p id="par0050" class="elsevierStylePara elsevierViewall">O presente estudo mostrou que a detec&#231;&#227;o de MCPyV &#233; significativamente maior em amostras neopl&#225;sicas e pr&#233;&#8208;malignas combinadas&#44; embora a carga viral n&#227;o tenha seguido o mesmo padr&#227;o&#46; &#201; poss&#237;vel que a resposta inflamat&#243;ria e&#47;ou processos de transforma&#231;&#227;o no tecido lesado criem condi&#231;&#227;o mais permissiva para a replica&#231;&#227;o de baixo n&#237;vel de MCPyV&#44; ou a infec&#231;&#227;o por MCPyV promova estado permissivo que possibilita o desenvolvimento de les&#227;o tecidual&#47;transforma&#231;&#227;o celular&#46; Essas hip&#243;teses foram feitas principalmente para o desenvolvimento de CCM positivo para MCPyV&#46;<a class="elsevierStyleCrossRefs" href="#bib0115"><span class="elsevierStyleSup">8&#44;9</span></a> Um dos pilares do CCM positivo para MCPyV &#233; a integra&#231;&#227;o clonal do DNA viral antes ou nos est&#225;gios iniciais da prolifera&#231;&#227;o de c&#233;lulas tumorais&#44; o que se traduz em alta porcentagem de c&#233;lulas infectadas&#46;<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">1&#44;9</span></a> Isso n&#227;o foi observado no presente estudo&#44; apoiando o entendimento de que a integra&#231;&#227;o clonal de MCPyV &#233; relevante para o desenvolvimento do CCM&#44; mas n&#227;o para outros tipos de CPNM ou condi&#231;&#245;es pr&#233;&#8208;malignas&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Este &#233; o primeiro estudo a detectar HPyV6 em amostras de pele saud&#225;vel em uma popula&#231;&#227;o brasileira&#44; com relato anterior mostrando apenas uma amostra com DNA de HPyV6 detect&#225;vel em uma les&#227;o de sarcoma de Kaposi &#40;SK&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">10</span></a> Relatos de outros grupos populacionais mostram positividade mais alta &#40;14&#37; a 27&#44;6&#37;&#41; de HPyV6 em amostras de pele saud&#225;veis de indiv&#237;duos imunocompetentes&#46;<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">3&#44;11</span></a> Em conjunto&#44; esses resultados podem sugerir uma infec&#231;&#227;o geral menor em indiv&#237;duos brasileiros&#44; mas a certeza exigiria uma an&#225;lise populacional maior&#46; Al&#233;m disso&#44; o HPyV6 foi encontrado em 42&#44;3&#37; dos ceratoacantomas &#40;CA&#41;&#44; bem como com alta carga em uma &#250;nica les&#227;o de CA de um paciente com melanoma&#46;<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">12&#44;13</span></a> Neste estudo&#44; entretanto&#44; a presen&#231;a de HPyV6 n&#227;o foi detectada em amostras de CA&#44; mas isso pode ser devido ao pequeno tamanho da amostra &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>3&#41;&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">Outro achado digno de nota &#233; que o HPyV6 apresentou maior porcentagem de c&#233;lulas infectadas em amostras de pele saud&#225;vel&#44; bem como em les&#245;es em &#225;reas com baixa exposi&#231;&#227;o solar &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;012&#41;&#46; A carga viral n&#227;o mostrou signific&#226;ncia vari&#225;vel&#46; A presen&#231;a de HPyV6 em todos os tipos de amostras com carga semelhante indica que a infec&#231;&#227;o n&#227;o &#233; afetada positiva ou negativamente por altera&#231;&#245;es teciduais ou processos tumorig&#234;nicos&#46; O contr&#225;rio tamb&#233;m pode ser deduzido&#58; que a infec&#231;&#227;o por HPyV6 parece n&#227;o favorecer nem dificultar tais processos&#44; tornando improv&#225;vel um mecanismo oncog&#234;nico sin&#233;rgico por meio de mera infec&#231;&#227;o&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Os presentes achados de cargas virais semelhantes independentemente do tipo de amostra &#40;les&#227;o&#44; pele perilesional e pele normal&#41; indicam que a presen&#231;a viral n&#227;o est&#225; condicionada &#224; presen&#231;a ou aus&#234;ncia de les&#227;o neopl&#225;sica&#46; Isso leva a algumas hip&#243;teses n&#227;o mutuamente exclusivas&#58; i&#41; a dispers&#227;o viral &#233; independente do desenvolvimento da les&#227;o e o v&#237;rus pode estar presente antes do in&#237;cio do desenvolvimento da les&#227;o&#59; ii&#41; o v&#237;rus se dissemina de ou para a les&#227;o de forma vari&#225;vel&#44; sem participar do processo oncog&#234;nico&#59; iii&#41; a infec&#231;&#227;o viral promove um estado permissivo para transforma&#231;&#227;o celular e&#44; ap&#243;s o in&#237;cio do processo oncog&#234;nico&#44; o v&#237;rus n&#227;o &#233; mais detectado na les&#227;o devido a um mecanismo <span class="elsevierStyleItalic">hit&#8208;and&#8208;run</span>&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">14</span></a> Considerando este &#250;ltimo&#44; as prote&#237;nas do ant&#237;geno T dos poliomav&#237;rus humanos&#44; que s&#227;o conhecidas por possu&#237;rem propriedades oncog&#234;nicas&#44;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">15</span></a> poderiam induzir a transforma&#231;&#227;o maligna sem a necessidade de persist&#234;ncia viral&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Conclus&#227;o</span><p id="par0070" class="elsevierStylePara elsevierViewall">Os achados de maior porcentagem de c&#233;lulas infectadas por HPyV6 na pele normal e MCPyV sendo mais frequente no grupo neopl&#225;sico e pr&#233;&#8208;maligno s&#227;o intrigantes&#46; No geral&#44; esses resultados aumentam o conhecimento sobre infec&#231;&#245;es por HPyV em diferentes CPNM&#44; embora uma amostra maior possa gerar novas correla&#231;&#245;es&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Suporte financeiro</span><p id="par0075" class="elsevierStylePara elsevierViewall">Este estudo foi financiado pelo FUNADERM &#40;Fundo de Apoio &#224; Dermatologia&#41;&#46; Este estudo tamb&#233;m foi parcialmente financiado pela FAPERJ &#40;Funda&#231;&#227;o de Pesquisa do Rio de Janeiro&#41; e Coordena&#231;&#227;o de Aperfei&#231;oamento de Pessoal de N&#237;vel Superior &#40;CAPES&#41; &#8211; C&#243;digo Financeiro 001&#46; Varella RB&#46; Recebeu suporte financeiro parcial do Conselho Nacional de Desenvolvimento Cient&#237;fico e Tecnol&#243;gico &#8211; CNPq&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Contribui&#231;&#227;o dos autores</span><p id="par0080" class="elsevierStylePara elsevierViewall">Marianna Venceslau&#58; Aprova&#231;&#227;o da vers&#227;o final do manuscrito&#59; concep&#231;&#227;o e planejamento do estudo&#59; elabora&#231;&#227;o e reda&#231;&#227;o do manuscrito&#59; obten&#231;&#227;o&#44; an&#225;lise e interpreta&#231;&#227;o dos dados&#59; revis&#227;o cr&#237;tica da literatura&#59; revis&#227;o cr&#237;tica do manuscrito&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">Gabriella Costa&#58; Aprova&#231;&#227;o da vers&#227;o final do manuscrito&#59; obten&#231;&#227;o&#44; an&#225;lise e interpreta&#231;&#227;o dos dados&#59; revis&#227;o cr&#237;tica da literatura&#59; revis&#227;o cr&#237;tica do manuscrito&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">Maria Angelica Guimar&#227;es&#58; Aprova&#231;&#227;o da vers&#227;o final do manuscrito&#59; concep&#231;&#227;o e planejamento do estudo&#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; revis&#227;o cr&#237;tica da literatura&#59; revis&#227;o cr&#237;tica do manuscrito&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Rafael Varella&#58; An&#225;lise estat&#237;stica&#59; Aprova&#231;&#227;o da vers&#227;o final do manuscrito&#59; concep&#231;&#227;o e planejamento do estudo&#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; revis&#227;o cr&#237;tica do manuscrito&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">Flavio Luz&#58; Aprova&#231;&#227;o da vers&#227;o final do manuscrito&#59; concep&#231;&#227;o e planejamento do estudo&#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; revis&#227;o cr&#237;tica do manuscrito&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Conflito de interesses</span><p id="par0105" class="elsevierStylePara elsevierViewall">Nenhum&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Fundamentos</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Poliomav&#237;rus humanos&#44; como MCPyV e HPyV6&#44; s&#227;o frequentemente encontrados como parte da microbiota da pele saud&#225;vel e t&#234;m sido associados ao carcinoma de c&#233;lulas de Merkel &#40;CCM&#41; e dermatoses pruriginosas e discerat&#243;ticas&#44; respectivamente&#46; Sua presen&#231;a em outros tipos de afec&#231;&#245;es da pele varia muito dependendo do tipo de les&#227;o e da popula&#231;&#227;o&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Objetivo</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Analisar comparativamente a presen&#231;a de MCPyV e HPyV6 em c&#226;ncer de pele n&#227;o melanoma e pele saud&#225;vel&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">M&#233;todos</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Foram utilizadas t&#233;cnicas de qPCR para quantificar esses pat&#243;genos em CPNM&#44; doen&#231;as pr&#233;&#8208;malignas e pele saud&#225;vel de 87 pacientes&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Resultados</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">MCPyV foi detectado em mais de 40&#37; das amostras&#44; enquanto HPyV6 em 9&#44;6&#37;&#46; A carga de MCPyV foi maior em carcinomas espinocelulares &#40;CEC&#41; em compara&#231;&#227;o com carcinomas basocelulares &#40;CBC&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;016&#41;&#44; e HPyV6 apresentou maior porcentagem de c&#233;lulas infectadas em &#225;reas de baixa exposi&#231;&#227;o solar&#44; bem como na pele normal &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;012&#41;&#46; Concord&#226;ncia razo&#225;vel &#40;kappa<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;301&#41; foi encontrada entre a detec&#231;&#227;o de MCPyV nas les&#245;es e sua respectiva pele perilesional&#44; indicando processo aleat&#243;rio de dissemina&#231;&#227;o local do v&#237;rus&#46;</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Limita&#231;&#245;es do estudo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">A falta de amostra maior de diferentes tipos de les&#245;es e an&#225;lises de express&#227;o de prote&#237;nas limita os achados de correla&#231;&#227;o&#46;</p><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Conclus&#227;o</span>&#58; Este &#233; o primeiro relato de detec&#231;&#227;o de HPyV6 na pele saud&#225;vel de uma popula&#231;&#227;o brasileira&#44; mas o papel de ambos os poliomav&#237;rus no CPNM ainda n&#227;o foi demonstrado&#46;</p></span>"
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Detec&#231;&#227;o &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&#37; c&#233;lulas infectadas&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">4&#44;1&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">4&#44;65 E&#8208;03&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">0&nbsp;\t\t\t\t\t\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">&#8211;&nbsp;\t\t\t\t\t\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">&#8211;&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"><span class="elsevierStyleHsp" style=""></span>N&#227;o maligna&nbsp;\t\t\t\t\t\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">20&#44;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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;74 E<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>04&nbsp;\t\t\t\t\t\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">4&#44;21 E&#8208;02&nbsp;\t\t\t\t\t\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">5&#44;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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;91 E<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>03&nbsp;\t\t\t\t\t\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">2&#44;32 E&#8208;01&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  " colspan="7" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="7" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Exposi&#231;&#227;o solar da les&#227;o</span></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"><span class="elsevierStyleHsp" style=""></span>Alta&nbsp;\t\t\t\t\t\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">32&#44;5&nbsp;\t\t\t\t\t\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">3&#44;24 E<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>04&nbsp;\t\t\t\t\t\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">4&#44;88 E&#8208;02&nbsp;\t\t\t\t\t\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">7&#44;3&nbsp;\t\t\t\t\t\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">2&#44;00 E<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>03&nbsp;\t\t\t\t\t\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">4&#44;6 E&#8208;04&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"><span class="elsevierStyleHsp" style=""></span>Moderada&nbsp;\t\t\t\t\t\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">4&#44;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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;40 E<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>04&nbsp;\t\t\t\t\t\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">4&#44;82 E&#8208;03&nbsp;\t\t\t\t\t\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">1&#44;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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#44;23 E<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>03&nbsp;\t\t\t\t\t\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">1&#44;95 E&#8208;08&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
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Baixa&nbsp;\t\t\t\t\t\t\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">3&#44;6&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\ttop\n
                  \t\t\t\t">2&#44;99 E<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>03&nbsp;\t\t\t\t\t\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">1&#44;24 E&#8208;02&nbsp;\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\ttop\n
                  \t\t\t\t">1&#44;1&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">8&#44;11 E&#8208;011</span><a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">18&#44;3&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1&#44;58 E<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>04&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#44;82 E&#8208;02&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">5&#44;8&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">2&#44;10 E<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>03&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">5&#44;54 E&#8208;02&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">2&#44;9&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleBold">8&#44;00 E&#8208;01</span><a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
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          "pt" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Concord&#226;ncia da detec&#231;&#227;o de MCPyV em les&#227;o de pele e tecido perilesional correlacionado</p>"
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Artigo original
Quantificação dos poliomavírus humanos MCPyV e HPyV6 em lesões cutâneas malignas e não malignas
Marianna T. Venceslaua,
Autor para correspondência
venceslaumarianna@gmail.com

Autor para correspondência.
, Gabriella R.M. da Costaa, Maria Angelica A.M. Guimarãesa, Rafael B. Varellab, Flavio B. Luzc
a Departamento de Medicina Preventiva, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brasil
b Departamento de Microbiologia e Parasitologia, Instituto Biomédico, Universidade Federal Fluminense, Niterói, RJ, Brasil
c Departamento de Medicina Clínica, Setor de Dermatologia, Hospital Universitário Antônio Pedro, Universidade Federal Fluminense, Niterói, RJ, Brasil
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por outro lado&#44; tamb&#233;m parece infectar a pele cronicamente sem manifesta&#231;&#227;o cl&#237;nica&#44; mas tem sido associado a dermatoses pruriginosas e discerat&#243;ticas&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">2</span></a> Embora essas associa&#231;&#245;es sejam estabelecidas&#44; ambos os v&#237;rus foram encontrados em diferentes les&#245;es&#44; notadamente em c&#226;ncer de pele n&#227;o melanoma &#40;CPNM&#41;&#44; bem como em pele saud&#225;vel&#44; e parecem constituir parte da flora da pele em adultos saud&#225;veis&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">3</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">O MCPyV foi investigado em rela&#231;&#227;o ao envolvimento no processo multifatorial de outros CPNM al&#233;m do CCM&#44; seja pela persist&#234;ncia do v&#237;rus na les&#227;o ou como contribuinte inicial para a oncog&#234;nese&#46; Em rela&#231;&#227;o ao HPyV6&#44; as mesmas quest&#245;es podem ser apresentadas em decorr&#234;ncia de seu tropismo epitelial e express&#227;o de prote&#237;nas potencialmente oncog&#234;nicas &#40;ant&#237;genos T&#41;&#46; Dado o tropismo observado de MCPyV e HPyV6 para c&#233;lulas epiteliais&#44; a natureza multifatorial da tumorig&#234;nese e a conhecida associa&#231;&#227;o com doen&#231;as cut&#226;neas correlacionadas&#44; objetivou&#8208;se investigar o DNA desses poliomav&#237;rus humanos com o intuito de elucidar seu poss&#237;vel envolvimento em processos neopl&#225;sicos&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Expandindo um relato anterior&#44; no qual o grupo dos autores observou a presen&#231;a de MCPyV no CBC por meio de abordagem qualitativa&#44; com 25&#44;7&#37; de positividade viral&#44;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">4</span></a> aqui objetivou&#8208;se avaliar e quantificar sua presen&#231;a em v&#225;rias les&#245;es cut&#226;neas malignas e n&#227;o malignas em um popula&#231;&#227;o brasileira&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">M&#233;todo</span><p id="par0020" class="elsevierStylePara elsevierViewall">Foram coletadas 181 amostras congeladas de les&#227;o&#44; pele perilesional e pele normal provenientes de 87 pacientes atendidos no Hospital Universit&#225;rio Ant&#244;nio Pedro &#40;HUAP&#8208;UFF&#41;&#44; entre setembro de 2017 e dezembro de 2018&#46; Dados sobre idade&#44; sexo&#44; estado imunol&#243;gico&#44; etnia e localiza&#231;&#227;o do tumor foram coletados durante a entrevista com o m&#233;dico examinador&#46; A etnia&#44; classificada como &#8216;branca&#8217; ou &#8216;n&#227;o branca&#8217;&#44; foi definida pelo dermatologista de acordo com o fototipo do paciente&#44; enquanto a localiza&#231;&#227;o do tumor foi usada para inferir a exposi&#231;&#227;o solar &#40;alta&#44; moderada ou baixa&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">5</span></a> O diagn&#243;stico histopatol&#243;gico de todas as les&#245;es foi realizado pelo Departamento de Patologia do HUAP&#8208;UFF&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Em rela&#231;&#227;o &#224; amostragem&#44; as bi&#243;psias das les&#245;es consistiram em bi&#243;psias por <span class="elsevierStyleItalic">shaving</span> das les&#245;es&#44; bi&#243;psias da pele perilesional removida pela equipe cir&#250;rgica para garantir a remo&#231;&#227;o completa do tumor&#44; posteriormente confirmada como &#8220;livre de les&#227;o&#8221; por histopatologia&#44; e amostras de pele normal foram obtidas no procedimento para fechar a incis&#227;o cir&#250;rgica&#46; Todas as amostras foram fragmentadas e digeridas com proteinase K &#40;Promega&#174; &#8211; Madison&#44; EUA&#41;&#44; e o DNA foi extra&#237;do utilizando&#8208;se kit comercial de acordo com as instru&#231;&#245;es do fabricante &#40;RTP&#174; DNA&#47;RNA Kit &#8211; Molecular Stratec Biomedical &#8211; Berlim&#44; Alemanha&#41;&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">O DNA de MCPyV e HPyV6 foi quantificado por ensaios TaqMan&#174; qPCR com base em protocolos descritos anteriormente&#46;<a class="elsevierStyleCrossRefs" href="#bib0105"><span class="elsevierStyleSup">6&#44;7</span></a> O gene beta&#8208;globina tamb&#233;m foi amplificado via qPCR para inferir a porcentagem de c&#233;lulas infectadas &#40;DNAviralgenebeta&#8722;globina&#47;2&#41;&#46; A an&#225;lise estat&#237;stica foi realizada com o <span class="elsevierStyleItalic">software</span> SPSS v&#46; 20 &#40;SPSS Inc&#46; &#8211; Chicago&#44; IL&#44; Estados Unidos&#41;&#46; O consentimento informado por escrito foi obtido de todos os indiv&#237;duos que concordaram em participar&#46; Este estudo foi aprovado pelo Comit&#234; de &#201;tica da Universidade&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Resultados</span><p id="par0035" class="elsevierStylePara elsevierViewall">As caracter&#237;sticas demogr&#225;ficas e cl&#237;nicas dos 87 pacientes com CPNM est&#227;o resumidas na <a class="elsevierStyleCrossRef" href="#tbl0005">tabela 1</a>&#46; No geral&#44; a maioria foi classificada como sendo de etnia branca &#40;80&#44;5&#37;&#41;&#44; do sexo feminino &#40;55&#44;2&#37;&#41;&#44; acima de 65 anos &#40;58&#44;1&#37;&#41; e teve o CPNM diagnosticado em &#225;reas com alta exposi&#231;&#227;o ao sol &#40;70&#44;2&#37;&#41;&#59; o carcinoma basocelular &#40;CBC&#41; foi o tipo histopatol&#243;gico mais frequente &#40;60&#44;9&#37;&#41;&#46; As frequ&#234;ncias virais de acordo com idade&#44; sexo e etnia n&#227;o foram significativas&#46; Outras les&#245;es encontradas&#44; classificadas como pr&#233;&#8208;malignas&#44; inclu&#237;ram elastose solar&#44; ceratoacantoma&#44; doen&#231;a de Bowen e hidradenite&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0040" class="elsevierStylePara elsevierViewall">A detec&#231;&#227;o de MCPyV foi elevada no total de bi&#243;psias estudadas &#40;40&#44;2&#37;&#41; em compara&#231;&#227;o com HPyV6 &#40;9&#44;6&#37;&#41;&#46; Embora a detec&#231;&#227;o tenha sido estatisticamente semelhante por tipo de les&#227;o &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">tabela 2</a>&#41;&#44; o MCPyV foi mais frequente em amostras neopl&#225;sicas e pr&#233;&#8208;malignas em conjunto do que em amostras n&#227;o malignas &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;047&#41;&#46; As cargas de MCPyV e porcentagem de c&#233;lulas infectadas n&#227;o foram associadas ao tipo de les&#227;o&#44; tipo de amostra e exposi&#231;&#227;o solar&#46; Curiosamente&#44; a porcentagem de c&#233;lulas infectadas com HPyV6 foi maior &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;012&#41; em amostras de &#225;reas com baixa exposi&#231;&#227;o solar e pele normal&#44; embora a amostragem baixa exija cautela&#46; As cargas de MCPyV foram maiores no subtipo CEC do que no CBC &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;016&#41;&#44; mas n&#227;o em porcentagem de c&#233;lulas infectadas &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;721&#59; dados n&#227;o mostrados&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0045" class="elsevierStylePara elsevierViewall">A concord&#226;ncia da detec&#231;&#227;o de MCPyV entre les&#227;o e pele perilesional foi razo&#225;vel &#40;kappa<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;301&#41;&#44; indicando dissemina&#231;&#227;o viral modesta ao redor da les&#227;o &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">tabela 3</a>&#41;&#46; A baixa taxa de detec&#231;&#227;o de HPyV6 tornou esta an&#225;lise inconclusiva&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Discuss&#227;o</span><p id="par0050" class="elsevierStylePara elsevierViewall">O presente estudo mostrou que a detec&#231;&#227;o de MCPyV &#233; significativamente maior em amostras neopl&#225;sicas e pr&#233;&#8208;malignas combinadas&#44; embora a carga viral n&#227;o tenha seguido o mesmo padr&#227;o&#46; &#201; poss&#237;vel que a resposta inflamat&#243;ria e&#47;ou processos de transforma&#231;&#227;o no tecido lesado criem condi&#231;&#227;o mais permissiva para a replica&#231;&#227;o de baixo n&#237;vel de MCPyV&#44; ou a infec&#231;&#227;o por MCPyV promova estado permissivo que possibilita o desenvolvimento de les&#227;o tecidual&#47;transforma&#231;&#227;o celular&#46; Essas hip&#243;teses foram feitas principalmente para o desenvolvimento de CCM positivo para MCPyV&#46;<a class="elsevierStyleCrossRefs" href="#bib0115"><span class="elsevierStyleSup">8&#44;9</span></a> Um dos pilares do CCM positivo para MCPyV &#233; a integra&#231;&#227;o clonal do DNA viral antes ou nos est&#225;gios iniciais da prolifera&#231;&#227;o de c&#233;lulas tumorais&#44; o que se traduz em alta porcentagem de c&#233;lulas infectadas&#46;<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">1&#44;9</span></a> Isso n&#227;o foi observado no presente estudo&#44; apoiando o entendimento de que a integra&#231;&#227;o clonal de MCPyV &#233; relevante para o desenvolvimento do CCM&#44; mas n&#227;o para outros tipos de CPNM ou condi&#231;&#245;es pr&#233;&#8208;malignas&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Este &#233; o primeiro estudo a detectar HPyV6 em amostras de pele saud&#225;vel em uma popula&#231;&#227;o brasileira&#44; com relato anterior mostrando apenas uma amostra com DNA de HPyV6 detect&#225;vel em uma les&#227;o de sarcoma de Kaposi &#40;SK&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">10</span></a> Relatos de outros grupos populacionais mostram positividade mais alta &#40;14&#37; a 27&#44;6&#37;&#41; de HPyV6 em amostras de pele saud&#225;veis de indiv&#237;duos imunocompetentes&#46;<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">3&#44;11</span></a> Em conjunto&#44; esses resultados podem sugerir uma infec&#231;&#227;o geral menor em indiv&#237;duos brasileiros&#44; mas a certeza exigiria uma an&#225;lise populacional maior&#46; Al&#233;m disso&#44; o HPyV6 foi encontrado em 42&#44;3&#37; dos ceratoacantomas &#40;CA&#41;&#44; bem como com alta carga em uma &#250;nica les&#227;o de CA de um paciente com melanoma&#46;<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">12&#44;13</span></a> Neste estudo&#44; entretanto&#44; a presen&#231;a de HPyV6 n&#227;o foi detectada em amostras de CA&#44; mas isso pode ser devido ao pequeno tamanho da amostra &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>3&#41;&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">Outro achado digno de nota &#233; que o HPyV6 apresentou maior porcentagem de c&#233;lulas infectadas em amostras de pele saud&#225;vel&#44; bem como em les&#245;es em &#225;reas com baixa exposi&#231;&#227;o solar &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;012&#41;&#46; A carga viral n&#227;o mostrou signific&#226;ncia vari&#225;vel&#46; A presen&#231;a de HPyV6 em todos os tipos de amostras com carga semelhante indica que a infec&#231;&#227;o n&#227;o &#233; afetada positiva ou negativamente por altera&#231;&#245;es teciduais ou processos tumorig&#234;nicos&#46; O contr&#225;rio tamb&#233;m pode ser deduzido&#58; que a infec&#231;&#227;o por HPyV6 parece n&#227;o favorecer nem dificultar tais processos&#44; tornando improv&#225;vel um mecanismo oncog&#234;nico sin&#233;rgico por meio de mera infec&#231;&#227;o&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Os presentes achados de cargas virais semelhantes independentemente do tipo de amostra &#40;les&#227;o&#44; pele perilesional e pele normal&#41; indicam que a presen&#231;a viral n&#227;o est&#225; condicionada &#224; presen&#231;a ou aus&#234;ncia de les&#227;o neopl&#225;sica&#46; Isso leva a algumas hip&#243;teses n&#227;o mutuamente exclusivas&#58; i&#41; a dispers&#227;o viral &#233; independente do desenvolvimento da les&#227;o e o v&#237;rus pode estar presente antes do in&#237;cio do desenvolvimento da les&#227;o&#59; ii&#41; o v&#237;rus se dissemina de ou para a les&#227;o de forma vari&#225;vel&#44; sem participar do processo oncog&#234;nico&#59; iii&#41; a infec&#231;&#227;o viral promove um estado permissivo para transforma&#231;&#227;o celular e&#44; ap&#243;s o in&#237;cio do processo oncog&#234;nico&#44; o v&#237;rus n&#227;o &#233; mais detectado na les&#227;o devido a um mecanismo <span class="elsevierStyleItalic">hit&#8208;and&#8208;run</span>&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">14</span></a> Considerando este &#250;ltimo&#44; as prote&#237;nas do ant&#237;geno T dos poliomav&#237;rus humanos&#44; que s&#227;o conhecidas por possu&#237;rem propriedades oncog&#234;nicas&#44;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">15</span></a> poderiam induzir a transforma&#231;&#227;o maligna sem a necessidade de persist&#234;ncia viral&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Conclus&#227;o</span><p id="par0070" class="elsevierStylePara elsevierViewall">Os achados de maior porcentagem de c&#233;lulas infectadas por HPyV6 na pele normal e MCPyV sendo mais frequente no grupo neopl&#225;sico e pr&#233;&#8208;maligno s&#227;o intrigantes&#46; No geral&#44; esses resultados aumentam o conhecimento sobre infec&#231;&#245;es por HPyV em diferentes CPNM&#44; embora uma amostra maior possa gerar novas correla&#231;&#245;es&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Suporte financeiro</span><p id="par0075" class="elsevierStylePara elsevierViewall">Este estudo foi financiado pelo FUNADERM &#40;Fundo de Apoio &#224; Dermatologia&#41;&#46; Este estudo tamb&#233;m foi parcialmente financiado pela FAPERJ &#40;Funda&#231;&#227;o de Pesquisa do Rio de Janeiro&#41; e Coordena&#231;&#227;o de Aperfei&#231;oamento de Pessoal de N&#237;vel Superior &#40;CAPES&#41; &#8211; C&#243;digo Financeiro 001&#46; Varella RB&#46; Recebeu suporte financeiro parcial do Conselho Nacional de Desenvolvimento Cient&#237;fico e Tecnol&#243;gico &#8211; CNPq&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Contribui&#231;&#227;o dos autores</span><p id="par0080" class="elsevierStylePara elsevierViewall">Marianna Venceslau&#58; Aprova&#231;&#227;o da vers&#227;o final do manuscrito&#59; concep&#231;&#227;o e planejamento do estudo&#59; elabora&#231;&#227;o e reda&#231;&#227;o do manuscrito&#59; obten&#231;&#227;o&#44; an&#225;lise e interpreta&#231;&#227;o dos dados&#59; revis&#227;o cr&#237;tica da literatura&#59; revis&#227;o cr&#237;tica do manuscrito&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">Gabriella Costa&#58; Aprova&#231;&#227;o da vers&#227;o final do manuscrito&#59; obten&#231;&#227;o&#44; an&#225;lise e interpreta&#231;&#227;o dos dados&#59; revis&#227;o cr&#237;tica da literatura&#59; revis&#227;o cr&#237;tica do manuscrito&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">Maria Angelica Guimar&#227;es&#58; Aprova&#231;&#227;o da vers&#227;o final do manuscrito&#59; concep&#231;&#227;o e planejamento do estudo&#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; revis&#227;o cr&#237;tica da literatura&#59; revis&#227;o cr&#237;tica do manuscrito&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Rafael Varella&#58; An&#225;lise estat&#237;stica&#59; Aprova&#231;&#227;o da vers&#227;o final do manuscrito&#59; concep&#231;&#227;o e planejamento do estudo&#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; revis&#227;o cr&#237;tica do manuscrito&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">Flavio Luz&#58; Aprova&#231;&#227;o da vers&#227;o final do manuscrito&#59; concep&#231;&#227;o e planejamento do estudo&#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; revis&#227;o cr&#237;tica do manuscrito&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Conflito de interesses</span><p id="par0105" class="elsevierStylePara elsevierViewall">Nenhum&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Fundamentos</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Poliomav&#237;rus humanos&#44; como MCPyV e HPyV6&#44; s&#227;o frequentemente encontrados como parte da microbiota da pele saud&#225;vel e t&#234;m sido associados ao carcinoma de c&#233;lulas de Merkel &#40;CCM&#41; e dermatoses pruriginosas e discerat&#243;ticas&#44; respectivamente&#46; Sua presen&#231;a em outros tipos de afec&#231;&#245;es da pele varia muito dependendo do tipo de les&#227;o e da popula&#231;&#227;o&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Objetivo</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Analisar comparativamente a presen&#231;a de MCPyV e HPyV6 em c&#226;ncer de pele n&#227;o melanoma e pele saud&#225;vel&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">M&#233;todos</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Foram utilizadas t&#233;cnicas de qPCR para quantificar esses pat&#243;genos em CPNM&#44; doen&#231;as pr&#233;&#8208;malignas e pele saud&#225;vel de 87 pacientes&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Resultados</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">MCPyV foi detectado em mais de 40&#37; das amostras&#44; enquanto HPyV6 em 9&#44;6&#37;&#46; A carga de MCPyV foi maior em carcinomas espinocelulares &#40;CEC&#41; em compara&#231;&#227;o com carcinomas basocelulares &#40;CBC&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;016&#41;&#44; e HPyV6 apresentou maior porcentagem de c&#233;lulas infectadas em &#225;reas de baixa exposi&#231;&#227;o solar&#44; bem como na pele normal &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;012&#41;&#46; Concord&#226;ncia razo&#225;vel &#40;kappa<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;301&#41; foi encontrada entre a detec&#231;&#227;o de MCPyV nas les&#245;es e sua respectiva pele perilesional&#44; indicando processo aleat&#243;rio de dissemina&#231;&#227;o local do v&#237;rus&#46;</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Limita&#231;&#245;es do estudo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">A falta de amostra maior de diferentes tipos de les&#245;es e an&#225;lises de express&#227;o de prote&#237;nas limita os achados de correla&#231;&#227;o&#46;</p><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Conclus&#227;o</span>&#58; Este &#233; o primeiro relato de detec&#231;&#227;o de HPyV6 na pele saud&#225;vel de uma popula&#231;&#227;o brasileira&#44; mas o papel de ambos os poliomav&#237;rus no CPNM ainda n&#227;o foi demonstrado&#46;</p></span>"
        "secciones" => array:5 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Fundamentos"
          ]
          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Objetivo"
          ]
          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "M&#233;todos"
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          3 => array:2 [
            "identificador" => "abst0020"
            "titulo" => "Resultados"
          ]
          4 => array:2 [
            "identificador" => "abst0025"
            "titulo" => "Limita&#231;&#245;es do estudo"
          ]
        ]
      ]
    ]
    "NotaPie" => array:2 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0020">Como citar este artigo&#58; Venceslau MT&#44; Costa GRM&#44; Guimar&#227;es MAAM&#44; Varella RB&#44; Luz FB&#46; Quantification of human polyomaviruses MCPyV and HPyV6 in malignant and non&#8208;malignant skin lesions&#46; An Bras Dermatol&#46; 2023&#59;98&#58;198&#8211;202&#46;</p>"
      ]
      1 => array:2 [
        "etiqueta" => "&#9734;&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0025">Trabalho realizado no Departamento de Medicina Preventiva&#44; Hospital Universit&#225;rio Clementino Fraga Filho&#44; Universidade Federal do Rio de Janeiro&#44; Rio de Janeiro&#44; RJ&#44; Brasil e Departamento de Medicina Cl&#237;nica&#44; Setor de Dermatologia&#44; Hospital Universit&#225;rio Ant&#244;nio Pedro&#44; Universidade Federal Fluminense&#44; Niter&#243;i&#44; RJ&#44; Brasil&#46;</p>"
      ]
    ]
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                  \t\t\t\t">67 &#40;17&#8211;91&#41;<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Alta&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">127 &#40;70&#44;2&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Moderada&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  " align="left" valign="\n
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          "leyenda" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Os resultados estatisticamente significativos &#40;p &#60;<span class="elsevierStyleHsp" style=""></span>0&#44;05&#41; est&#227;o em negrito&#46;</p>"
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">16<a class="elsevierStyleCrossRef" href="#tblfn0010"><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">3&#44;73 E<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>04&nbsp;\t\t\t\t\t\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">3&#44;89 E&#8208;02&nbsp;\t\t\t\t\t\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">4&#44;5&nbsp;\t\t\t\t\t\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">1&#44;97 E<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>03&nbsp;\t\t\t\t\t\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">2&#44;49 E&#8208;04&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"><span class="elsevierStyleHsp" style=""></span>Pr&#233;&#8208;maligna&nbsp;\t\t\t\t\t\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">4&#44;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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#44;5 E<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>04&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="left" valign="\n
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                  \t\t\t\t">4&#44;65 E&#8208;03&nbsp;\t\t\t\t\t\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">0&nbsp;\t\t\t\t\t\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
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                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\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
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                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
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                  \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"><span class="elsevierStyleHsp" style=""></span>N&#227;o maligna&nbsp;\t\t\t\t\t\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">20&#44;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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;74 E<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>04&nbsp;\t\t\t\t\t\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">4&#44;21 E&#8208;02&nbsp;\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\ttop\n
                  \t\t\t\t">5&#44;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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;91 E<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>03&nbsp;\t\t\t\t\t\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">2&#44;32 E&#8208;01&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  " colspan="7" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="7" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Exposi&#231;&#227;o solar da les&#227;o</span></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"><span class="elsevierStyleHsp" style=""></span>Alta&nbsp;\t\t\t\t\t\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">32&#44;5&nbsp;\t\t\t\t\t\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">3&#44;24 E<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>04&nbsp;\t\t\t\t\t\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">4&#44;88 E&#8208;02&nbsp;\t\t\t\t\t\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">7&#44;3&nbsp;\t\t\t\t\t\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">2&#44;00 E<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>03&nbsp;\t\t\t\t\t\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">4&#44;6 E&#8208;04&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"><span class="elsevierStyleHsp" style=""></span>Moderada&nbsp;\t\t\t\t\t\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">4&#44;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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;40 E<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>04&nbsp;\t\t\t\t\t\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">4&#44;82 E&#8208;03&nbsp;\t\t\t\t\t\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">1&#44;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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#44;23 E<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>03&nbsp;\t\t\t\t\t\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">1&#44;95 E&#8208;08&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"><span class="elsevierStyleHsp" style=""></span>Baixa&nbsp;\t\t\t\t\t\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">3&#44;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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#44;99 E<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>03&nbsp;\t\t\t\t\t\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">1&#44;24 E&#8208;02&nbsp;\t\t\t\t\t\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">1&#44;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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#44;59 E<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>03&nbsp;\t\t\t\t\t\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"><span class="elsevierStyleBold">8&#44;11 E&#8208;011</span><a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">b</span></a>&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  " colspan="7" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="7" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Tipo de amostra</span></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"><span class="elsevierStyleHsp" style=""></span>Les&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">18&#44;3&nbsp;\t\t\t\t\t\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">1&#44;58 E<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>04&nbsp;\t\t\t\t\t\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">4&#44;82 E&#8208;02&nbsp;\t\t\t\t\t\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">5&#44;8&nbsp;\t\t\t\t\t\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">2&#44;10 E<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>03&nbsp;\t\t\t\t\t\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">2&#44;5 E&#8208;04&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"><span class="elsevierStyleHsp" style=""></span>Perilesional&nbsp;\t\t\t\t\t\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">11&#44;2&nbsp;\t\t\t\t\t\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">3&#44;73 E<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>04&nbsp;\t\t\t\t\t\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">5&#44;54 E&#8208;02&nbsp;\t\t\t\t\t\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">2&#44;9&nbsp;\t\t\t\t\t\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">4&#44;72 E<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>02&nbsp;\t\t\t\t\t\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">3&#44;9 E&#8208;04&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"><span class="elsevierStyleHsp" style=""></span>Pele normal&nbsp;\t\t\t\t\t\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">10&#44;7&nbsp;\t\t\t\t\t\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">6&#44;23 E<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>03&nbsp;\t\t\t\t\t\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">3&#44;71 E&#8208;03&nbsp;\t\t\t\t\t\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">1&#44;2&nbsp;\t\t\t\t\t\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">2&#44;72 E<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>03&nbsp;\t\t\t\t\t\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"><span class="elsevierStyleBold">8&#44;00 E&#8208;01</span><a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
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