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La relaci&#243;n entre VPH y el c&#225;ncer de piel se ha sustentado en varias premisas como la asociaci&#243;n epidemiol&#243;gica observada entre las verrugas y los carcinoma epidermoides cut&#225;neos &#40;CEC&#41; en pacientes con epidermodisplasia verruciforme<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a>&#44; la coexistencia de signos histol&#243;gicos de infecci&#243;n viral y displasia epitelial en una misma biopsia<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6&#44;7</span></a> o la identificaci&#243;n de ADN del VPH en muchos CCNM<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8&#44;9</span></a>&#46; En un principio se intent&#243; extrapolar los mecanismos identificados en los VPH mucosos oncog&#233;nicos para determinar cu&#225;les ser&#237;an las estrategias o mecanismos moleculares de los VPH-&#946; &#40;y VPH-&#947;&#41; para inducir carcinog&#233;nesis cut&#225;nea&#46; Sin embargo&#44; se comprob&#243; que las v&#237;as de actuaci&#243;n de los tipos cut&#225;neos son diferentes&#44; bastante m&#225;s complejas y posiblemente en colaboraci&#243;n con otros cofactores como la radiaci&#243;n ultravioleta &#40;UV&#41; o la inmunosupresi&#243;n&#46; De estudios moleculares realizados en cultivos celulares se desprende que las dianas principales de los VPH-&#946; se centran en mecanismos antiapopt&#243;ticos y en el bloqueo de las v&#237;as protectoras de la integridad del genoma encargadas de reparar el da&#241;o provocado por la radiaci&#243;n UV&#46; En este sentido&#44; se ha observado que los VPH-&#946; 8 y 20 tienen la capacidad de bloquear la acci&#243;n de las prote&#237;nas proapopt&#243;ticas BAK y BAX<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a>&#44; cuya acci&#243;n es similar pero independiente de la p53&#46; As&#237; mismo&#44; se ha identificado otra prote&#237;na &#40;prote&#237;na XRCC1&#41; reparadora de d&#237;meros de timidina inducidos por la radiaci&#243;n UV&#44; que puede ser interceptada por algunos VPH-&#946; como el HPV<span class="elsevierStyleHsp" style=""></span>8<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a>&#46; Las prote&#237;nas VPH E6 y E7 son oncoprote&#237;nas codificadas por el virus&#46; Estudios recientes han examinado el papel de estas prote&#237;nas en la transformaci&#243;n a CEC en pacientes trasplantados&#46; Se han encontrado transcripciones E6&#47;E7 en VPH<span class="elsevierStyleHsp" style=""></span>8&#44; 9 y 15 en queratosis act&#237;nicas y CEC&#44; sugiriendo un papel activo de VPH en la patogenia de estas lesiones<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a>&#46; Adem&#225;s se ha descubierto que los VPH<span class="elsevierStyleHsp" style=""></span>8 y VPH<span class="elsevierStyleHsp" style=""></span>5 tienen una capacidad inhibitoria sobre la interleucina-8 que participa en la estimulaci&#243;n de una respuesta inmunitaria que controla aquellas c&#233;lulas da&#241;adas por la radiaci&#243;n UV<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a>&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">Sin embargo&#44; la falta de resultados consistentes de ADN del VPH en el c&#225;ncer de piel&#44; el frecuente hallazgo de VPH en la piel normal y la falta de identificaci&#243;n de un grupo de &#171;alto riesgo&#187; de VPH en el c&#225;ncer de piel cuestionan el papel del VPH en el desarrollo de CCNM&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">En el presente estudio tratamos de determinar la prevalencia y el espectro de los tipos de VPH en piel tumoral y piel sana perilesional de pacientes trasplantados renales y pacientes inmunocompetentes&#44; as&#237; como evaluar la influencia de diferentes factores cl&#237;nicos en la prevalencia del VPH en el c&#225;ncer cut&#225;neo&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">M&#233;todos</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Dise&#241;o del estudio y pacientes</span><p id="par0025" class="elsevierStylePara elsevierViewall">Se determin&#243; la presencia de ADN de VPH en muestras tumorales y piel sana perilesional de pacientes inmunodeprimidos e inmunocompetentes&#46; Se estudiaron un total de 60 pacientes &#40;30 trasplantados renales y 30 inmunocompetentes&#41; remitidos desde la consulta de nefrolog&#237;a a la consulta de dermatolog&#237;a del Hospital Universitario Doctor Peset de Valencia&#44; para la valoraci&#243;n de lesiones sospechosas de CCNM durante el periodo comprendido entre enero de 2010 a enero de 2012&#46; El estudio fue aprobado por el Comit&#233; de &#201;tica del Hospital&#46; Se obtuvo consentimiento informado de todos los pacientes&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Los pacientes fueron entrevistados por medio de un cuestionario estructurado para recopilar informaci&#243;n relativa a las variables potenciales de confusi&#243;n&#58; edad&#44; sexo&#44; fototipo &#40;seg&#250;n la clasificaci&#243;n de Fitzpatrick&#41;&#44; exposici&#243;n solar ocupacional &#40;consider&#225;ndola alta cuando el paciente trabajaba o hab&#237;a trabajado la mayor parte de su jornada laboral al aire libre&#41;&#44; as&#237; como historia pasada o actual de verrugas y queratosis act&#237;nicas&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Las caracter&#237;sticas de los pacientes se muestran en la <a class="elsevierStyleCrossRef" href="#tbl0010">tabla 2</a>&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Muestras</span><p id="par0040" class="elsevierStylePara elsevierViewall">Se obtuvieron 2 biopsias de cada paciente de la siguiente manera&#58; despu&#233;s de la extirpaci&#243;n de la lesi&#243;n sospechosa se tom&#243; una biopsia <span class="elsevierStyleItalic">punch</span> de 3<span class="elsevierStyleHsp" style=""></span>mm del centro de la lesi&#243;n &#40;muestra tumoral&#41; y otra biopsia <span class="elsevierStyleItalic">punch</span> de 3<span class="elsevierStyleHsp" style=""></span>mm del extremo del huso de la misma pieza quir&#250;rgica libre de lesi&#243;n &#40;piel sana perilesional&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0005">fig&#46; 1</a>&#41;&#46; Las biopsias se almacenaron en fresco a &#8211;80<span class="elsevierStyleHsp" style=""></span>&#176;C en criotubos individuales hasta su procesamiento&#46; El resto de la pieza quir&#250;rgica fue fijada en formol al 10&#37; y embebida en parafina para su diagn&#243;stico histopatol&#243;gico&#46; Se obtuvieron un total de 120 biopsias&#58; 60 de pacientes trasplantados &#40;30 biopsias de piel tumoral y 30 de piel sana perilesional&#41; y 60 de pacientes inmunocompetentes &#40;30 pacientes de piel tumoral y 30 de piel sana perilesional&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0045" class="elsevierStylePara elsevierViewall">Las muestras tumorales de pacientes inmunodeprimidos e inmunocompetentes se compon&#237;an de 30 lesiones en cada grupo&#58; 7 CEC&#44; 10 CEC <span class="elsevierStyleItalic">in situ</span> y 13 carcinomas basocelulares &#40;CBC&#41;&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">Las muestras de piel eran consideradas de &#225;reas fotoexpuestas si se recog&#237;an de las &#225;reas de la cara&#44; la nuca o el cuello&#44; la zona anterior del t&#243;rax&#44; la parte superior de la espalda&#44; el dorso del antebrazo o la regi&#243;n pretibial&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">M&#233;todo de deteci&#243;n virus del papiloma humano</span><p id="par0055" class="elsevierStylePara elsevierViewall">La extracci&#243;n del ADN y tipificaci&#243;n del VPH se llev&#243; a cabo seg&#250;n el m&#233;todo descrito por Harwood et al&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a>&#46; Para la extracci&#243;n de ADN de las muestras se utiliz&#243; el kit Maxwell 16 FFPE Tissue LEV DNA purification kit<span class="elsevierStyleSup">&#174;</span>&#46; La identificaci&#243;n de los distintos tipos de VPH se llev&#243; a cabo mediante PCR <span class="elsevierStyleItalic">nested</span> y posterior secuenciaci&#243;n&#46; Se emplearon 100<span class="elsevierStyleHsp" style=""></span>ng de ADN para la amplificaci&#243;n en un volumen final de 25<span class="elsevierStyleHsp" style=""></span>&#956;l &#40;para las 2 amplificaciones&#41; con 3&#44;5<span class="elsevierStyleHsp" style=""></span>mM de MgCl<span class="elsevierStyleInf">2</span>&#44; 10<span class="elsevierStyleHsp" style=""></span>mM Tris HCL&#44; 50<span class="elsevierStyleHsp" style=""></span>mM KCL&#44; 0&#44;1&#37; trit&#243;n X-100&#44; 0&#44;2<span class="elsevierStyleHsp" style=""></span>mM de cada uno de los deoxinucle&#243;tidos trifosfato&#44; 0&#44;75<span class="elsevierStyleHsp" style=""></span>&#956;M de cada cebador&#44; DMSO al 5&#37; y 1&#44;25 U Taq DNA polimerasa &#40;Promega<span class="elsevierStyleSup">&#174;</span>&#41;&#46; Desde la primera a la segunda amplificaci&#243;n se traspasaron 2&#44;5<span class="elsevierStyleHsp" style=""></span>&#956;l&#46; La primera amplificaci&#243;n const&#243; de 45 ciclos de amplificaci&#243;n de 94<span class="elsevierStyleHsp" style=""></span>&#176;C de desnaturalizaci&#243;n &#40;1&#44;5<span class="elsevierStyleHsp" style=""></span>min&#41;&#44; 50<span class="elsevierStyleHsp" style=""></span>&#176;C de apareamiento &#40;1&#44;5<span class="elsevierStyleHsp" style=""></span>min&#41; y 72<span class="elsevierStyleHsp" style=""></span>&#176;C de extensi&#243;n &#40;1&#44;5<span class="elsevierStyleHsp" style=""></span>min&#41;&#46; La segunda amplificaci&#243;n const&#243; de 30 ciclos de amplificaci&#243;n de 94<span class="elsevierStyleHsp" style=""></span>&#176;C de desnaturalizaci&#243;n &#40;1&#44;5<span class="elsevierStyleHsp" style=""></span>min&#41;&#44; 50<span class="elsevierStyleHsp" style=""></span>&#176;C de apareamiento &#40;1&#44;5<span class="elsevierStyleHsp" style=""></span>min&#41; y 72<span class="elsevierStyleHsp" style=""></span>&#176;C de extensi&#243;n &#40;1&#44;5<span class="elsevierStyleHsp" style=""></span>min&#41;&#46; Los cebadores utilizados en la primera amplificaci&#243;n corresponden a los descritos en la literatura con nombre FAP59 y FAP64<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a>&#44; con posiciones situadas en los nucle&#243;tidos 5&#46;981 a 6&#46;001 &#40;iniciador cadena directa&#44; FAP59&#41; y 6&#46;458 a 6&#46;436 &#40;iniciador cadena complementaria&#44; FAP64&#41;&#46; Los cebadores utilizados en la segunda amplificaci&#243;n corresponden a los descritos en la literatura con nombre FAP 6085F y FAP6319R<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a>&#44; con posiciones situadas en los nucle&#243;tidos 6&#46;085 a 6&#46;104 &#40;iniciador cadena directa&#44; FAP6085F&#41; y 6&#46;319 a 6&#46;296 &#40;iniciador cadena complementaria&#44; FAP6319R&#41;&#46; La posici&#243;n de estos <span class="elsevierStyleItalic">primers</span> est&#225; referida al genoma de VPH<span class="elsevierStyleHsp" style=""></span>8&#46; La detecci&#243;n del amplificado de 235 pares de bases se realiz&#243; en gel de agarosa al 3&#37;&#46; El amplificado fue purificado mediante columnas &#40;Purelink<span class="elsevierStyleSup">&#174;</span>&#44; Invitrogen&#41;&#46; La reacci&#243;n de secuenciaci&#243;n se llev&#243; a cabo en un volumen final de 10<span class="elsevierStyleHsp" style=""></span>&#956;l mediante BigDye Terminador v3&#46;1 Cycle sequencing kit<span class="elsevierStyleSup">&#174;</span> &#40;Applied Biosystems&#41; en las condiciones descritas por el fabricante&#46; El perfil de amplificaci&#243;n empleado fue de 25 ciclos con 10<span class="elsevierStyleHsp" style=""></span>seg a 94<span class="elsevierStyleHsp" style=""></span>&#176;C&#44; 10<span class="elsevierStyleHsp" style=""></span>min a 50<span class="elsevierStyleHsp" style=""></span>&#176;C y 2<span class="elsevierStyleHsp" style=""></span>min a 60<span class="elsevierStyleHsp" style=""></span>&#176;C&#46; Una vez finalizada la reacci&#243;n de secuenciaci&#243;n esta fue purificada mediante alcoholes &#40;etanol al 100&#37; y al 70&#37;&#41; y el producto final se resuspendi&#243; en formamida desionizada&#46; El producto final fue secuenciado en ABI PRISM<span class="elsevierStyleSup">&#174;</span> 310 &#40;Applied Biosystems&#41; y se analiz&#243; la secuencia en la base de datos del NCBI usando el algoritmo blast-n&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">An&#225;lisis estad&#237;stico</span><p id="par0060" class="elsevierStylePara elsevierViewall">Las variables categ&#243;ricas se describen como frecuencias y porcentajes y las variables continuas como media y desviaci&#243;n estandar &#40;DE&#41;&#46; Las diferencias en la distribuci&#243;n de las variables entre los grupos fueron evaluadas con la prueba Chi-cuadrado &#40;&#967;<span class="elsevierStyleSup">2</span>&#41; o prueba exacta de Fisher para las variables categ&#243;ricas y el an&#225;lisis de la varianza &#40;ANOVA&#41; para los datos continuos&#46; <span class="elsevierStyleItalic">Odds ratio</span> &#40;OR&#41; e intervalos de confianza &#40;IC&#41; al 95&#37; fueron calculados&#59; OR se estim&#243; tambi&#233;n ajustada a la exposici&#243;n solar ocupacional&#44; fototipo y localizaci&#243;n de la muestra&#46; Se utiliz&#243; el an&#225;lisis de regresi&#243;n log&#237;stica m&#250;ltiple para identificar las variables de forma independiente asociadas a la presencia de VPH en las muestras de piel&#46; Los an&#225;lisis se realizaron con el paquete estad&#237;stico SPSS&#44; v&#46; 19&#46; La significaci&#243;n estad&#237;stica se fij&#243; en p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;05&#46;</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Resultados</span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Virus del papiloma humano en pacientes inmunodeprimidos y pacientes inmunocompetentes</span><p id="par0065" class="elsevierStylePara elsevierViewall">El ADN del VPH fue detectado con mayor frecuencia en pacientes inmunodeprimidos en comparaci&#243;n con los pacientes inmunocompetentes&#46; El VPH fue detectado en un total de 44 de las 60 muestras &#40;73&#44;3&#37;&#41; en pacientes trasplantados&#44; frente 32 de las 60 muestras &#40;53&#44;3&#37;&#41; en pacientes inmunocompetentes&#44; siendo estas diferencias significativas &#40;OR ajustada 3&#44;4 &#91;1&#44;2-9&#44;6&#93;&#41;&#46; Al comparar los distintos g&#233;neros de VPH el m&#225;s prevalente fue el VPH-&#946;&#44; aunque no encontramos diferencias significativas en la prevalencia de VPH entre pacientes inmunodeprimidos e inmunocompetentes &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">tabla 3</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Virus del papiloma humano en piel tumoral y piel sana perilesional</span><p id="par0070" class="elsevierStylePara elsevierViewall">Se detect&#243; ADN del VPH con mayor frecuencia en piel sana perilesional que en piel tumoral&#44; tanto en pacientes inmunodeprimidos como en inmunocompetentes&#46; Al comparar los distintos g&#233;neros de VPH entre piel tumoral y piel sana perilesional el g&#233;nero VPH-&#946;&#44; en concreto la especie &#946;-1 fue el m&#225;s prevalente&#44; pero no se encontraron diferencias entre los grupos&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">La <a class="elsevierStyleCrossRef" href="#tbl0020">tabla 4</a> muestra las tasas de detecci&#243;n de ADN del VPH y OR ajustada para las muestras de los pacientes inmunodeprimidos &#40;lesi&#243;n y perilesi&#243;n&#41; y pacientes inmunocompetentes &#40;lesi&#243;n y perilesi&#243;n&#41;&#46; Ajustamos la OR al fototipo&#44; exposici&#243;n solar y localizaci&#243;n de la muestra&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Tipos de virus del papiloma humano</span><p id="par0080" class="elsevierStylePara elsevierViewall">Los tipos VPH del g&#233;nero &#946; fueron los m&#225;s frecuentes&#44; encontr&#225;ndose en 34&#47;60 &#40;56&#44;5&#37;&#41; de las muestras de pacientes inmunodeprimidos y en 26&#47;60 &#40;43&#44;3&#37;&#41; de las muestras de pacientes inmunocompetentes&#46; Dentro del g&#233;nero VPH-&#946; la especie VPH-&#946;1 fue la m&#225;s prevalente&#44; siendo el tipo m&#225;s frecuente el VPH-20&#44; aunque sin encontrarse diferencias significativas entre los grupos&#46; Solo detectamos una muestra de VPH-&#945; en un paciente inmunocompetente&#46; VPH-&#947; mostr&#243; una fuerte asociaci&#243;n a pacientes inmunodeprimidos&#44; aunque sin alcanzar significaci&#243;n estad&#237;stica&#46; En 6 determinaciones la PCR para VPH fue positiva de forma d&#233;bil&#44; no pudi&#233;ndose secuenciar al tener poca cantidad de ADN viral&#46; Se detectaron 4 muestras de VPH no clasificados en Genbank &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">tabla 4</a>&#41;&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">Se detectaron infecciones mixtas &#40;por m&#250;ltiples tipos de VPH&#41; en 29 de las 120 determinaciones&#44; siendo m&#225;s frecuentes en pacientes inmunodeprimidos &#40;17&#47;60&#41; que en inmunocompetentes &#40;12&#47;60&#41;&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Factores de riesgo</span><p id="par0090" class="elsevierStylePara elsevierViewall">Los pacientes inmunodeprimidos e inmunocompetentes fueron similares en edad y sexo&#46; Tampoco difirieron significativamente con respecto a la exposici&#243;n solar&#44; localizaci&#243;n del tumor&#44; fotototipo o historia de verrugas o queratosis act&#237;nicas&#46; La localizaci&#243;n del tumor en &#225;reas fotoexpuestas fue la &#250;nica variable asociada de forma significativa a un mayor riesgo de VPH en pacientes inmunodeprimidos&#46; En pacientes inmunocompetentes la exposici&#243;n ocupacional alta&#44; la localizaci&#243;n en &#225;reas expuestas y el fototipo bajo fueron significativamente m&#225;s frecuentes en los pacientes positivos para el VPH&#46; En pacientes inmunodeprimidos el riesgo de positividad del VPH tambi&#233;n fue mayor en pacientes con queratosis act&#237;nicas y verrugas&#44; pero las diferencias no fueron estad&#237;sticamente significativas &#40;<a class="elsevierStyleCrossRef" href="#tbl0025">tabla 5</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0025"></elsevierMultimedia></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Virus del papiloma humano en piel tumoral</span><p id="par0095" class="elsevierStylePara elsevierViewall">Recogimos las muestras de 60 lesiones tumorales&#58; 30 de pacientes inmunodeprimidos &#40;7 CEC&#44; 10 CEC <span class="elsevierStyleItalic">in situ</span> y 13 CBC&#41; y 30 de pacientes inmunocompetentes &#40;7 CEC&#44; 10 CEC <span class="elsevierStyleItalic">in situ</span> y 13 CBC&#41;&#46; La presencia de VPH fue m&#225;s frecuente en CEC <span class="elsevierStyleItalic">in situ</span> tanto en pacientes inmunodeprimidos como en inmunocompetentes&#44; detect&#225;ndose en 8&#47;10 &#40;80&#37;&#41; de los CEC <span class="elsevierStyleItalic">in situ</span> en pacientes inmunodeprimidos y en 6&#47;10 &#40;60&#37;&#41; de los CEC <span class="elsevierStyleItalic">in situ</span> de los pacientes inmunocompetentes&#46; La menor prevalencia de VPH la encontramos en los CBC&#44; tanto en inmunodeprimidos como en inmunocompetentes&#44; aunque estos resultados no alcanzaron significaci&#243;n estad&#237;stica &#40;<a class="elsevierStyleCrossRef" href="#tbl0030">tabla 6</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0030"></elsevierMultimedia></span></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Discusi&#243;n</span><p id="par0100" class="elsevierStylePara elsevierViewall">En este estudio se ha examinado una poblaci&#243;n de pacientes inmunodeprimidos e inmunocompetentes para identificar la prevalencia y el espectro de los tipos de VPH presentes en el tejido tumoral y en la piel sana perilesional&#46; La mayor prevalencia de VPH encontrada en pacientes inmunodeprimidos frente inmunocompetentes concuerda con otros art&#237;culos publicados previamente&#46; En el estudio de Harwood et al&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> se compara por la t&#233;cnica de PCR degenerada la prevalencia de VPH en 148 muestras&#58; 85 muestras de pacientes inmunodeprimidos &#40;44 CEC&#44; 24 CBC y 17 lesiones premalignas&#58; queratosis act&#237;nicas o CEC <span class="elsevierStyleItalic">in situ</span>&#41; y 63 de pacientes inmunocompetentes &#40;22 CEC&#44; 30 CBC y 11 lesiones premalignas&#41; encontrando una mayor prevalencia de VPH en las lesiones de los pacientes inmunodeprimidos en comparaci&#243;n con los pacientes inmunocompetentes &#40;82 frente 36&#37;&#59; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">Al comparar la prevalencia de VPH entre piel tumoral y piel sana perilesional la presencia de VPH ha sido mayor en piel sana perilesional que en piel tumoral&#44; tanto en pacientes inmunodeprimidos como en inmunocompetentes&#44; aunque estos resultados no han alcanzado significaci&#243;n estad&#237;stica&#46; La alta prevalencia de ADN del VPH en piel sana perilesional&#44; tanto en pacientes inmunodeprimidos como en inmunocompetentes&#44; concuerda con los hallazgos de estudios anteriores que sugieren que el ADN del VPH se encuentra ampliamente distribuido en la piel de la poblaci&#243;n general<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">18&#44;19</span></a>&#46; Estudios realizados en personas inmunocompetentes han encontrado ADN del VPH en 67-74&#37; de los pelos arrancados<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">19&#44;20</span></a> y en el 69-80&#37; de los frotis de piel<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a>&#46; Estos estudios&#44; junto con nuestros datos&#44; sugieren que la presencia de ADN de VPH es generalizada en piel de apariencia normal&#46; En otros estudios&#44; en cambio&#44; se detect&#243; ADN del VPH con mayor frecuencia en piel tumoral que en piel sana&#46; En el estudio de Forslund et al&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> se compar&#243; la presencia de VPH en CCNM&#44; queratosis act&#237;nicas y piel sana del mismo paciente&#44; hall&#225;ndose una prevalencia de VPH mayor en la piel tumoral que en la piel sana&#44; y llegaron a la conclusi&#243;n que la especie VPH-&#946;2 se asociaba a CEC&#46; En nuestro estudio no determinamos la presencia de VPH en queratosis act&#237;nicas y la mayor&#237;a de tumores incluidos fueron CBC&#46; En este punto debemos puntualizar que la mayor&#237;a de trabajos relacionan la infecci&#243;n del VPH con el CEC<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a>&#46; Los trabajos que intentan buscar una asociaci&#243;n entre infecci&#243;n por VPH y CBC son menores<a class="elsevierStyleCrossRefs" href="#bib0120"><span class="elsevierStyleSup">24&#44;25</span></a>&#44; y la gran mayor&#237;a no encuentran una asociaci&#243;n estad&#237;sticamente significativa&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">No hemos encontrado diferencias significativas en el espectro de tipos de VPH entre las 2 poblaciones&#44; si bien el g&#233;nero VPH-&#946; fue el m&#225;s prevalente&#44; sobre todo la especie VPH-&#946;1&#46; Datos similares se muestran en otros art&#237;culos<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a>&#44; aunque muchos de estos trabajos se basan en la clasificaci&#243;n taxon&#243;mica cl&#225;sica de VPH en&#58; mucosos&#44; cut&#225;neos o asociados a epidermodisplasia verruciforme &#40;EV&#41;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a>&#46; Seg&#250;n la clasificaci&#243;n de Villiers de 2004<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> &#40;que clasifica los VPH en 16 g&#233;neros&#41; los tipos anteriormente clasificados como VPH-EV ahora se incluyen en el g&#233;nero &#946;&#58; VPH-&#946;1 y VPH-&#946;2&#46; En el estudio de Asgari et al&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> la especie m&#225;s prevalente fue VPH-&#946;2&#44; aunque en este estudio&#44; como en el nuestro&#44; el tipo m&#225;s frecuente detectado fue el VPH-20 &#40;perteneciente a VPH-&#946;1&#41;&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">Las muestras de &#225;reas fotoexpuestas mostraron mayor prevalencia de ADN del VPH tanto en pacientes inmunodeprimidos como en inmunocompetentes&#46; Nuestro estudio apoya la teor&#237;a de la importante interacci&#243;n de la luz UV y la presencia de VPH&#46; La radiaci&#243;n UV tambi&#233;n se asoci&#243; con CCNM en pacientes VPH-<span class="elsevierStyleItalic">beta</span> positivos en el estudio de Bouwes Bavinck et al&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a>&#46; Al estudiar los posibles factores de confusi&#243;n solo la localizaci&#243;n del tumor en &#225;reas fotoexpuestas se asoci&#243; con un mayor riesgo de VPH en pacientes inmunodeprimidos&#46; En pacientes inmunocompetentes la exposici&#243;n solar ocupacional alta&#44; la localizaci&#243;n del tumor en &#225;reas fotoexpuestas y el fototipo bajo tambi&#233;n se asociaron con un mayor riesgo de VPH de forma significativa&#46; El importante papel de la radiaci&#243;n UV tambi&#233;n se refleja en otros trabajos como el de Forslund et al&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a>&#44; donde el ADN del VPH tambi&#233;n se asoci&#243; de forma significativa con la exposici&#243;n al sol&#44; tanto en piel tumoral como en piel sana&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">Al comparar la presencia de VPH en las muestras tumorales la presencia de VPH fue mayor en los CEC <span class="elsevierStyleItalic">in situ</span> que en los CEC o CBC&#44; tanto en pacientes inmunodeprimidos como inmunocompetentes&#46; Este hallazgo coincide con los estudios que sostienen la teor&#237;a de que el VPH en el c&#225;ncer de piel se detecta con mayor frecuencia en las lesiones m&#225;s precoces como los CEC <span class="elsevierStyleItalic">in situ</span> y queratosis con displasia&#44; sugiriendo que la influencia del VPH se centrar&#237;a fundamentalmente en las etapas iniciales de la carcinog&#233;nesis cut&#225;nea&#44; m&#225;s que en la perpetuaci&#243;n tumoral<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">29&#44;30</span></a>&#46; En nuestro trabajo&#44; si bien no determinamos la presencia de VPH en queratosis act&#237;nicas&#44; la presencia de queratosis act&#237;nicas o verrugas se asoci&#243; a mayor riesgo de VPH en pacientes inmunodeprimidos&#44; aunque estos resultados no alcanzaron significaci&#243;n estad&#237;stica&#44; seguramente por el tama&#241;o muestral limitado&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">Los datos obtenidos en este estudio ponen de relieve las diferencias potencialmente importantes en la prevalencia de VPH de pacientes inmunodeprimidos e inmunocompetentes&#44; apoyando la compleja interacci&#243;n entre VPH&#44; la exposici&#243;n a la radiaci&#243;n UV y el estado de inmunosupresi&#243;n&#46; La mayor prevalencia de VPH encontrada en piel sana perilesional sugiere que el ADN del VPH se encuentra ampliamente distribuido en la poblaci&#243;n general&#46; Si bien no hemos encontrado correlaci&#243;n entre la presencia de VPH y el c&#225;ncer de piel hemos de tener en cuenta que se trata de una serie peque&#241;a&#44; de car&#225;cter informativo y que se necesitan estudios m&#225;s amplios para valorar la implicaci&#243;n del VPH en el c&#225;ncer de piel&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Responsabilidades &#233;ticas</span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Protecci&#243;n de personas y animales</span><p id="par0130" class="elsevierStylePara elsevierViewall">Los autores declaran que para esta investigaci&#243;n no se han realizado experimentos en seres humanos ni en animales&#46;</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Confidencialidad de los datos</span><p id="par0135" class="elsevierStylePara elsevierViewall">Los autores declaran que han seguido los protocolos de su centro de trabajo sobre la publicaci&#243;n de datos de pacientes y que todos los pacientes incluidos en el estudio han recibido informaci&#243;n suficiente y han dado su consentimiento informado por escrito para participar en dicho estudio&#46;</p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0155">Derecho a la privacidad y consentimiento informado</span><p id="par0140" class="elsevierStylePara elsevierViewall">Los autores declaran que en este art&#237;culo no aparecen datos de pacientes&#46;</p></span></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0160">Conflicto de intereses</span><p id="par0145" class="elsevierStylePara elsevierViewall">Los autores declaran que no tienen ning&#250;n conflicto de intereses</p></span></span>"
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          "titulo" => array:6 [
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              "titulo" => "Dise&#241;o del estudio y pacientes"
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              "titulo" => "M&#233;todo de deteci&#243;n virus del papiloma humano"
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              "titulo" => "An&#225;lisis estad&#237;stico"
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              "identificador" => "sec0040"
              "titulo" => "Virus del papiloma humano en pacientes inmunodeprimidos y pacientes inmunocompetentes"
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            1 => array:2 [
              "identificador" => "sec0045"
              "titulo" => "Virus del papiloma humano en piel tumoral y piel sana perilesional"
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            2 => array:2 [
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              "titulo" => "Tipos de virus del papiloma humano"
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              "titulo" => "Factores de riesgo"
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            4 => array:2 [
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              "titulo" => "Virus del papiloma humano en piel tumoral"
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          "titulo" => "Discusi&#243;n"
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              "titulo" => "Protecci&#243;n de personas y animales"
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              "titulo" => "Confidencialidad de los datos"
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            2 => array:2 [
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              "titulo" => "Derecho a la privacidad y consentimiento informado"
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          "titulo" => "Conflicto de intereses"
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          "titulo" => "Agradecimientos"
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    "pdfFichero" => "main.pdf"
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    "fechaRecibido" => "2013-07-19"
    "fechaAceptado" => "2013-10-27"
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            0 => "Virus del papiloma humano"
            1 => "C&#225;ncer de piel no melanoma"
            2 => "Reacci&#243;n en cadena de la polimerasa"
            3 => "Inmunosupresi&#243;n"
            4 => "Carcinoma epidermoide"
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            0 => "Human papillomavirus"
            1 => "Nonmelanoma skin cancer"
            2 => "Polymerase chain reaction"
            3 => "Immunosuppression"
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            5 => "Basal cell carcinoma"
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    "resumen" => array:2 [
      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<span class="elsevierStyleSectionTitle" id="sect0010">Antecedentes</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">La influencia del virus del papiloma humano &#40;VPH&#41; en el desarrollo de carcinoma cut&#225;neo no melanoma es un tema controvertido&#46; VPH-&#946; es el g&#233;nero m&#225;s frecuente relacionado con el desarrollo de c&#225;ncer de piel&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0015">Objetivos</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Analizar la prevalencia y espectro de los tipos de VPH presentes en piel tumoral y piel sana perilesional en pacientes inmunodeprimidos y pacientes inmunocompetentes&#44; as&#237; como evaluar la influencia de diferentes factores cl&#237;nicos en la prevalencia del VPH en c&#225;ncer de piel&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0020">M&#233;todos</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Se determin&#243; la presencia de VPH en 120 muestras mediante PCR <span class="elsevierStyleItalic">nested</span> y posterior secuenciaci&#243;n&#46; Se tom&#243; biopsia de piel de 30 pacientes trasplantados renales y de 30 pacientes inmunocompetentes con c&#225;ncer cut&#225;neo tanto de zona tumoral como de piel sana perilesional&#46; Se registraron las variables potenciales de confusi&#243;n&#46; Los datos fueron analizados utilizando an&#225;lisis de regresi&#243;n log&#237;stica multivariado&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0025">Resultados</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">ADN del VPH fue detectado en 44&#47;60 &#40;73&#44;3&#37;&#41; de las muestras de pacientes inmunodeprimidos y en 32&#47;60 &#40;53&#44;3&#37;&#41; de las muestras de pacientes inmunocompetentes &#40;OR ajustada 3&#44;4 &#91;1&#44;2-9&#44;6&#93;&#41;&#46; Al comparar la presencia de VPH en los 2 grupos entre piel tumoral y piel sana perilesional la presencia de VPH en piel sana perilesional fue mayor que en piel tumoral&#46; El g&#233;nero m&#225;s frecuente aislado fue el VPH-&#946;&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0030">Conclusi&#243;n</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Un amplio espectro de tipos de VPH&#44; la mayor&#237;a del g&#233;nero &#946;&#44; se encuentran en la piel de pacientes trasplantados e inmunocompetentes con c&#225;ncer cut&#225;neo&#46;</p>"
      ]
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span class="elsevierStyleSectionTitle" id="sect0040">Background</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">The influence of human papillomavirus &#40;HPV&#41; on the development of nonmelanoma skin cancer &#40;NMSC&#41; is a topic of debate&#46; HPV types from the beta genus &#40;HPV-&#946;&#41; have been most frequently associated with the development of skin cancer&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0045">Objectives</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">To analyze the prevalence and range of HPV types in NMSC lesions and healthy perilesional skin in immunodepressed and immunocompetent patients and to evaluate the influence of various clinical factors on the prevalence of HPV in skin cancer&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0050">Methods</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Nested polymerase chain reaction and sequencing were used to detect HPV in 120 NMSC samples obtained by biopsy from 30 kidney transplant recipients and 30 immunocompetent patients&#46; In all cases&#44; a sample was taken from the tumor site and the surrounding healthy skin&#46; Potential confounders were assessed and the data analyzed by multivariate logistic regression&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0055">Results</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">HPV DNA was detected in 44 &#40;73&#46;3&#37;&#41; of the 60 samples from immunodepressed patients and in 32 &#40;53&#46;3&#37;&#41; of the 60 samples from immunocompetent patients &#40;adjusted odds ratio&#44; 3&#46;4&#59; 95&#37; <span class="elsevierStyleSmallCaps">CI</span>&#44; 1&#46;2-9&#46;6&#41;&#46; In both groups of patients&#44; HPV was more common in healthy perilesional skin than in lesional skin&#46; HPV-&#946; was the most common type isolated&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0060">Conclusion</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">We found a wide range of HPV types &#40;mostly HPV-&#946;&#41; in the skin of kidney transplant recipients and immunocompetent patients with skin cancer&#46;</p>"
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                  \t\t\t\t" style="border-bottom: 2px solid black">G&#233;nero&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">Especie&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">Tipo&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">Otros tipos&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">Comentarios&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Beta&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">VPH-5&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">VPH-8&#44; 12&#44; 14&#44; 19&#44; 20&#44; 21&#44; 25&#44; 36&#44; 47&#44; 93&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Lesiones cut&#225;neas&#46; Com&#250;nmente asociado a lesiones en epidermodisplasia verruciforme &#40;EV&#41; o pacientes inmunodeprimidos&#46;Normalmente lesiones benignas&#44; pero tambi&#233;n asociado a lesiones malignas&#44; incluso en pacientes inmunocompetentes&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">2&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">VPH-9&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">VPH-15&#44; 17&#44; 22&#44; 23&#44; 37&#44; 38&#44; 80&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Lesiones cut&#225;neas&#46; Com&#250;nmente asociado a lesiones en EV o pacientes inmunodeprimidos&#46;Normalmente lesiones benignas&#44; pero tambi&#233;n asociado a lesiones malignas&#44; incluso en pacientes inmunocompetentes&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">3&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">VPH-49&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">VPH-75&#44; 76&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">Lesiones cut&#225;neas benignas&nbsp;\t\t\t\t\t\t\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="left" valign="\n
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                  \t\t\t\t">4&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">VPHcand92&nbsp;\t\t\t\t\t\t\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
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Lesiones cut&#225;neas premalignas y malignas&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">5&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">VPHcand96&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">&#8211;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Lesiones cut&#225;neas premalignas y malignas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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                  \t\t\t\t" style="border-bottom: 2px solid black">Pacientes inmunodeprimidos &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>30&#41;N&#46;<span class="elsevierStyleSup">o</span>&#47;total &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">72&#44;53<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>12&#44;57&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">15&#47;30 &#40;50&#44;0&#41;&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"><span class="elsevierStyleHsp" style=""></span>Zona fotoexpuesta&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">22&#47;30 &#40;73&#44;3&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">16&#47;30 &#40;53&#44;3&#41;&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"><span class="elsevierStyleHsp" style=""></span>Zona no fotoexpuesta&nbsp;\t\t\t\t\t\t\n
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                  """
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">7 &#40;23&#44;3&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#44;1 &#40;0&#44;6-7&#44;4&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;4 &#40;0&#44;5-4&#44;5&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Beta-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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6 &#40;20&#44;0&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5 &#40;16&#44;7&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3 &#40;10&#44;0&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;3&#44;3&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;3 &#40;0&#44;3-4&#44;6&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#44;2 &#40;0&#44;3-32&#44;9&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Beta- 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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;3&#44;3&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6 &#40;20&#44;0&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0 &#40;-&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5 &#40;16&#44;7&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;1 &#40;0&#44;1-1&#44;2&#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="char" valign="\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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Beta- 4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#40;3&#44;3&#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="char" valign="\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="char" valign="\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="char" valign="\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="char" valign="\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="char" valign="\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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Beta- 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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#40;3&#44;3&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;3&#44;3&#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="char" valign="\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="char" valign="\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="char" valign="\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  " 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">&#947;-papiloma virus</span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\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="elsevierStyleHsp" style=""></span>Todos VPH-&#947;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3 &#40;10&#44;0&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;6&#44;7&#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="char" valign="\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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;3&#44;3&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;5 &#40;0&#44;2-10&#44;1&#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="char" valign="\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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>VPH-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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;3&#44;3&#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="char" valign="\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="char" valign="\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="char" valign="\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="char" valign="\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="char" valign="\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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>VPH-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="char" valign="\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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;3&#44;3&#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="char" valign="\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="char" valign="\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="char" valign="\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="char" valign="\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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>VPH-10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;3&#44;3&#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="char" valign="\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="char" valign="\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="char" valign="\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="char" valign="\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="char" valign="\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  " 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  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">No clasificable VPH</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="char" valign="\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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;6&#44;7&#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="char" valign="\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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;6&#44;7&#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="char" valign="\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="char" valign="\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>
                  """
              ]
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            0 => array:3 [
              "identificador" => "tblfn0010"
              "etiqueta" => "a"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0010">An&#225;lisis pareado comparando VPH en zona lesional y piel sana perilesional en pacientes inmunodeprimidos&#46;</p>"
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            1 => array:3 [
              "identificador" => "tblfn0015"
              "etiqueta" => "b"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0015">An&#225;lisis pareado comparando VPH en zona lesional y piel sana perilesional en pacientes inmunocompetentes&#46;</p>"
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              "nota" => "<p class="elsevierStyleNotepara" id="npar0020">OR ajustada por localizaci&#243;n de la muestra&#44; fototipo y exposici&#243;n solar&#46;</p>"
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      5 => array:7 [
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        "tabla" => array:2 [
          "leyenda" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">PH positivo o negativo se refiere a VPH detectado o no detectado respectivamente en el total de las muestras &#40;lesi&#243;n y perilesi&#243;n&#41;&#46;</p>"
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                  \t\t\t\t" style="border-bottom: 2px solid black">Pacientes inmunodeprimidos</td><td class="td" title="\n
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                  \t\t\t\t">0 &#40;0&#44;1-1&#44;9&#41;&nbsp;\t\t\t\t\t\t\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"><span class="elsevierStyleHsp" style=""></span>Zona no fotoexpuesta&nbsp;\t\t\t\t\t\t\n
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Detección del virus del papiloma humano en muestras de cáncer cutáneo no melanoma y piel sana perilesional en pacientes trasplantados renales y pacientes inmunocompetentes
Detection of Human Papillomavirus in Nonmelanoma Skin Cancer Lesions and Healthy Perilesional Skin in Kidney Transplant Recipients and Immunocompetent Patients
J. Bernat-Garcíaa,
Autor para correspondencia
josefabernat@hotmail.com

Autor para correspondencia.
, M. Morales Suárez-Varelab, J.J. Vilata-Corellc, A. Marquina-Vilaa
a Servicio de Dermatología, Hospital Universitario Doctor Peset, Valencia, España
b Unidad de Salud Pública, Higiene y Sanidad Ambiental, Departamento de Medicina Preventiva y Salud Pública, Universitat de València, Valencia, España
c Servicio de Dermatología, Hospital General Universitario de Valencia, Valencia, España
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Introducci&#243;n</span><p id="par0005" class="elsevierStylePara elsevierViewall">El virus del papiloma humano &#40;VPH&#41; es un conocido factor de riesgo para el desarrollo de c&#225;ncer de cuello de &#250;tero<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;2</span></a>&#46; Tambi&#233;n es reconocida su implicaci&#243;n en la etiopatogenia del carcinoma epidermoide de las mucosas &#40;vulva&#44; pene&#44; ano&#41;&#44; o en el carcinoma epidermoide de cabeza y cuello &#40;faringe&#41;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a>&#46; Sin embargo&#44; su papel en el desarrollo del c&#225;ncer cut&#225;neo no melanoma &#40;CCNM&#41; es m&#225;s discutido&#46; Los estudios realizados para valorar la implicaci&#243;n del VPH en la oncog&#233;nesis cut&#225;nea son muy dispares&#44; en parte debido a las diferencias en los m&#233;todos utilizados para la detecci&#243;n y tipificaci&#243;n del VPH&#44; el tipo de muestra analizada&#44; as&#237; como la falta de inclusi&#243;n de potenciales factores de confusi&#243;n para el riesgo de c&#225;ncer de piel&#44; sobre todo aquellos relacionados con la exposici&#243;n solar&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">De acuerdo con la actual clasificaci&#243;n taxon&#243;mica<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a>&#44; la familia <span class="elsevierStyleItalic">Papillomaviridae</span> est&#225; compuesta por 16 g&#233;neros&#44; que se identifican con las letras griegas &#40;alfa&#44; beta&#44; gamma&#44; etc&#46;&#41;&#46; Cada g&#233;nero incluye una o varias especies&#44; que van numeradas&#44; y dentro de cada especie encontramos los tipos&#44; subtipos y variantes&#46; En la <a class="elsevierStyleCrossRef" href="#tbl0005">tabla 1</a> se muestra la clasificaci&#243;n del VPH del g&#233;nero beta&#46; La relaci&#243;n entre VPH y el c&#225;ncer de piel se ha sustentado en varias premisas como la asociaci&#243;n epidemiol&#243;gica observada entre las verrugas y los carcinoma epidermoides cut&#225;neos &#40;CEC&#41; en pacientes con epidermodisplasia verruciforme<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a>&#44; la coexistencia de signos histol&#243;gicos de infecci&#243;n viral y displasia epitelial en una misma biopsia<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6&#44;7</span></a> o la identificaci&#243;n de ADN del VPH en muchos CCNM<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8&#44;9</span></a>&#46; En un principio se intent&#243; extrapolar los mecanismos identificados en los VPH mucosos oncog&#233;nicos para determinar cu&#225;les ser&#237;an las estrategias o mecanismos moleculares de los VPH-&#946; &#40;y VPH-&#947;&#41; para inducir carcinog&#233;nesis cut&#225;nea&#46; Sin embargo&#44; se comprob&#243; que las v&#237;as de actuaci&#243;n de los tipos cut&#225;neos son diferentes&#44; bastante m&#225;s complejas y posiblemente en colaboraci&#243;n con otros cofactores como la radiaci&#243;n ultravioleta &#40;UV&#41; o la inmunosupresi&#243;n&#46; De estudios moleculares realizados en cultivos celulares se desprende que las dianas principales de los VPH-&#946; se centran en mecanismos antiapopt&#243;ticos y en el bloqueo de las v&#237;as protectoras de la integridad del genoma encargadas de reparar el da&#241;o provocado por la radiaci&#243;n UV&#46; En este sentido&#44; se ha observado que los VPH-&#946; 8 y 20 tienen la capacidad de bloquear la acci&#243;n de las prote&#237;nas proapopt&#243;ticas BAK y BAX<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a>&#44; cuya acci&#243;n es similar pero independiente de la p53&#46; As&#237; mismo&#44; se ha identificado otra prote&#237;na &#40;prote&#237;na XRCC1&#41; reparadora de d&#237;meros de timidina inducidos por la radiaci&#243;n UV&#44; que puede ser interceptada por algunos VPH-&#946; como el HPV<span class="elsevierStyleHsp" style=""></span>8<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a>&#46; Las prote&#237;nas VPH E6 y E7 son oncoprote&#237;nas codificadas por el virus&#46; Estudios recientes han examinado el papel de estas prote&#237;nas en la transformaci&#243;n a CEC en pacientes trasplantados&#46; Se han encontrado transcripciones E6&#47;E7 en VPH<span class="elsevierStyleHsp" style=""></span>8&#44; 9 y 15 en queratosis act&#237;nicas y CEC&#44; sugiriendo un papel activo de VPH en la patogenia de estas lesiones<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a>&#46; Adem&#225;s se ha descubierto que los VPH<span class="elsevierStyleHsp" style=""></span>8 y VPH<span class="elsevierStyleHsp" style=""></span>5 tienen una capacidad inhibitoria sobre la interleucina-8 que participa en la estimulaci&#243;n de una respuesta inmunitaria que controla aquellas c&#233;lulas da&#241;adas por la radiaci&#243;n UV<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a>&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">Sin embargo&#44; la falta de resultados consistentes de ADN del VPH en el c&#225;ncer de piel&#44; el frecuente hallazgo de VPH en la piel normal y la falta de identificaci&#243;n de un grupo de &#171;alto riesgo&#187; de VPH en el c&#225;ncer de piel cuestionan el papel del VPH en el desarrollo de CCNM&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">En el presente estudio tratamos de determinar la prevalencia y el espectro de los tipos de VPH en piel tumoral y piel sana perilesional de pacientes trasplantados renales y pacientes inmunocompetentes&#44; as&#237; como evaluar la influencia de diferentes factores cl&#237;nicos en la prevalencia del VPH en el c&#225;ncer cut&#225;neo&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">M&#233;todos</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Dise&#241;o del estudio y pacientes</span><p id="par0025" class="elsevierStylePara elsevierViewall">Se determin&#243; la presencia de ADN de VPH en muestras tumorales y piel sana perilesional de pacientes inmunodeprimidos e inmunocompetentes&#46; Se estudiaron un total de 60 pacientes &#40;30 trasplantados renales y 30 inmunocompetentes&#41; remitidos desde la consulta de nefrolog&#237;a a la consulta de dermatolog&#237;a del Hospital Universitario Doctor Peset de Valencia&#44; para la valoraci&#243;n de lesiones sospechosas de CCNM durante el periodo comprendido entre enero de 2010 a enero de 2012&#46; El estudio fue aprobado por el Comit&#233; de &#201;tica del Hospital&#46; Se obtuvo consentimiento informado de todos los pacientes&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Los pacientes fueron entrevistados por medio de un cuestionario estructurado para recopilar informaci&#243;n relativa a las variables potenciales de confusi&#243;n&#58; edad&#44; sexo&#44; fototipo &#40;seg&#250;n la clasificaci&#243;n de Fitzpatrick&#41;&#44; exposici&#243;n solar ocupacional &#40;consider&#225;ndola alta cuando el paciente trabajaba o hab&#237;a trabajado la mayor parte de su jornada laboral al aire libre&#41;&#44; as&#237; como historia pasada o actual de verrugas y queratosis act&#237;nicas&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Las caracter&#237;sticas de los pacientes se muestran en la <a class="elsevierStyleCrossRef" href="#tbl0010">tabla 2</a>&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Muestras</span><p id="par0040" class="elsevierStylePara elsevierViewall">Se obtuvieron 2 biopsias de cada paciente de la siguiente manera&#58; despu&#233;s de la extirpaci&#243;n de la lesi&#243;n sospechosa se tom&#243; una biopsia <span class="elsevierStyleItalic">punch</span> de 3<span class="elsevierStyleHsp" style=""></span>mm del centro de la lesi&#243;n &#40;muestra tumoral&#41; y otra biopsia <span class="elsevierStyleItalic">punch</span> de 3<span class="elsevierStyleHsp" style=""></span>mm del extremo del huso de la misma pieza quir&#250;rgica libre de lesi&#243;n &#40;piel sana perilesional&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0005">fig&#46; 1</a>&#41;&#46; Las biopsias se almacenaron en fresco a &#8211;80<span class="elsevierStyleHsp" style=""></span>&#176;C en criotubos individuales hasta su procesamiento&#46; El resto de la pieza quir&#250;rgica fue fijada en formol al 10&#37; y embebida en parafina para su diagn&#243;stico histopatol&#243;gico&#46; Se obtuvieron un total de 120 biopsias&#58; 60 de pacientes trasplantados &#40;30 biopsias de piel tumoral y 30 de piel sana perilesional&#41; y 60 de pacientes inmunocompetentes &#40;30 pacientes de piel tumoral y 30 de piel sana perilesional&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0045" class="elsevierStylePara elsevierViewall">Las muestras tumorales de pacientes inmunodeprimidos e inmunocompetentes se compon&#237;an de 30 lesiones en cada grupo&#58; 7 CEC&#44; 10 CEC <span class="elsevierStyleItalic">in situ</span> y 13 carcinomas basocelulares &#40;CBC&#41;&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">Las muestras de piel eran consideradas de &#225;reas fotoexpuestas si se recog&#237;an de las &#225;reas de la cara&#44; la nuca o el cuello&#44; la zona anterior del t&#243;rax&#44; la parte superior de la espalda&#44; el dorso del antebrazo o la regi&#243;n pretibial&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">M&#233;todo de deteci&#243;n virus del papiloma humano</span><p id="par0055" class="elsevierStylePara elsevierViewall">La extracci&#243;n del ADN y tipificaci&#243;n del VPH se llev&#243; a cabo seg&#250;n el m&#233;todo descrito por Harwood et al&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a>&#46; Para la extracci&#243;n de ADN de las muestras se utiliz&#243; el kit Maxwell 16 FFPE Tissue LEV DNA purification kit<span class="elsevierStyleSup">&#174;</span>&#46; La identificaci&#243;n de los distintos tipos de VPH se llev&#243; a cabo mediante PCR <span class="elsevierStyleItalic">nested</span> y posterior secuenciaci&#243;n&#46; Se emplearon 100<span class="elsevierStyleHsp" style=""></span>ng de ADN para la amplificaci&#243;n en un volumen final de 25<span class="elsevierStyleHsp" style=""></span>&#956;l &#40;para las 2 amplificaciones&#41; con 3&#44;5<span class="elsevierStyleHsp" style=""></span>mM de MgCl<span class="elsevierStyleInf">2</span>&#44; 10<span class="elsevierStyleHsp" style=""></span>mM Tris HCL&#44; 50<span class="elsevierStyleHsp" style=""></span>mM KCL&#44; 0&#44;1&#37; trit&#243;n X-100&#44; 0&#44;2<span class="elsevierStyleHsp" style=""></span>mM de cada uno de los deoxinucle&#243;tidos trifosfato&#44; 0&#44;75<span class="elsevierStyleHsp" style=""></span>&#956;M de cada cebador&#44; DMSO al 5&#37; y 1&#44;25 U Taq DNA polimerasa &#40;Promega<span class="elsevierStyleSup">&#174;</span>&#41;&#46; Desde la primera a la segunda amplificaci&#243;n se traspasaron 2&#44;5<span class="elsevierStyleHsp" style=""></span>&#956;l&#46; La primera amplificaci&#243;n const&#243; de 45 ciclos de amplificaci&#243;n de 94<span class="elsevierStyleHsp" style=""></span>&#176;C de desnaturalizaci&#243;n &#40;1&#44;5<span class="elsevierStyleHsp" style=""></span>min&#41;&#44; 50<span class="elsevierStyleHsp" style=""></span>&#176;C de apareamiento &#40;1&#44;5<span class="elsevierStyleHsp" style=""></span>min&#41; y 72<span class="elsevierStyleHsp" style=""></span>&#176;C de extensi&#243;n &#40;1&#44;5<span class="elsevierStyleHsp" style=""></span>min&#41;&#46; La segunda amplificaci&#243;n const&#243; de 30 ciclos de amplificaci&#243;n de 94<span class="elsevierStyleHsp" style=""></span>&#176;C de desnaturalizaci&#243;n &#40;1&#44;5<span class="elsevierStyleHsp" style=""></span>min&#41;&#44; 50<span class="elsevierStyleHsp" style=""></span>&#176;C de apareamiento &#40;1&#44;5<span class="elsevierStyleHsp" style=""></span>min&#41; y 72<span class="elsevierStyleHsp" style=""></span>&#176;C de extensi&#243;n &#40;1&#44;5<span class="elsevierStyleHsp" style=""></span>min&#41;&#46; Los cebadores utilizados en la primera amplificaci&#243;n corresponden a los descritos en la literatura con nombre FAP59 y FAP64<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a>&#44; con posiciones situadas en los nucle&#243;tidos 5&#46;981 a 6&#46;001 &#40;iniciador cadena directa&#44; FAP59&#41; y 6&#46;458 a 6&#46;436 &#40;iniciador cadena complementaria&#44; FAP64&#41;&#46; Los cebadores utilizados en la segunda amplificaci&#243;n corresponden a los descritos en la literatura con nombre FAP 6085F y FAP6319R<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a>&#44; con posiciones situadas en los nucle&#243;tidos 6&#46;085 a 6&#46;104 &#40;iniciador cadena directa&#44; FAP6085F&#41; y 6&#46;319 a 6&#46;296 &#40;iniciador cadena complementaria&#44; FAP6319R&#41;&#46; La posici&#243;n de estos <span class="elsevierStyleItalic">primers</span> est&#225; referida al genoma de VPH<span class="elsevierStyleHsp" style=""></span>8&#46; La detecci&#243;n del amplificado de 235 pares de bases se realiz&#243; en gel de agarosa al 3&#37;&#46; El amplificado fue purificado mediante columnas &#40;Purelink<span class="elsevierStyleSup">&#174;</span>&#44; Invitrogen&#41;&#46; La reacci&#243;n de secuenciaci&#243;n se llev&#243; a cabo en un volumen final de 10<span class="elsevierStyleHsp" style=""></span>&#956;l mediante BigDye Terminador v3&#46;1 Cycle sequencing kit<span class="elsevierStyleSup">&#174;</span> &#40;Applied Biosystems&#41; en las condiciones descritas por el fabricante&#46; El perfil de amplificaci&#243;n empleado fue de 25 ciclos con 10<span class="elsevierStyleHsp" style=""></span>seg a 94<span class="elsevierStyleHsp" style=""></span>&#176;C&#44; 10<span class="elsevierStyleHsp" style=""></span>min a 50<span class="elsevierStyleHsp" style=""></span>&#176;C y 2<span class="elsevierStyleHsp" style=""></span>min a 60<span class="elsevierStyleHsp" style=""></span>&#176;C&#46; Una vez finalizada la reacci&#243;n de secuenciaci&#243;n esta fue purificada mediante alcoholes &#40;etanol al 100&#37; y al 70&#37;&#41; y el producto final se resuspendi&#243; en formamida desionizada&#46; El producto final fue secuenciado en ABI PRISM<span class="elsevierStyleSup">&#174;</span> 310 &#40;Applied Biosystems&#41; y se analiz&#243; la secuencia en la base de datos del NCBI usando el algoritmo blast-n&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">An&#225;lisis estad&#237;stico</span><p id="par0060" class="elsevierStylePara elsevierViewall">Las variables categ&#243;ricas se describen como frecuencias y porcentajes y las variables continuas como media y desviaci&#243;n estandar &#40;DE&#41;&#46; Las diferencias en la distribuci&#243;n de las variables entre los grupos fueron evaluadas con la prueba Chi-cuadrado &#40;&#967;<span class="elsevierStyleSup">2</span>&#41; o prueba exacta de Fisher para las variables categ&#243;ricas y el an&#225;lisis de la varianza &#40;ANOVA&#41; para los datos continuos&#46; <span class="elsevierStyleItalic">Odds ratio</span> &#40;OR&#41; e intervalos de confianza &#40;IC&#41; al 95&#37; fueron calculados&#59; OR se estim&#243; tambi&#233;n ajustada a la exposici&#243;n solar ocupacional&#44; fototipo y localizaci&#243;n de la muestra&#46; Se utiliz&#243; el an&#225;lisis de regresi&#243;n log&#237;stica m&#250;ltiple para identificar las variables de forma independiente asociadas a la presencia de VPH en las muestras de piel&#46; Los an&#225;lisis se realizaron con el paquete estad&#237;stico SPSS&#44; v&#46; 19&#46; La significaci&#243;n estad&#237;stica se fij&#243; en p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;05&#46;</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Resultados</span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Virus del papiloma humano en pacientes inmunodeprimidos y pacientes inmunocompetentes</span><p id="par0065" class="elsevierStylePara elsevierViewall">El ADN del VPH fue detectado con mayor frecuencia en pacientes inmunodeprimidos en comparaci&#243;n con los pacientes inmunocompetentes&#46; El VPH fue detectado en un total de 44 de las 60 muestras &#40;73&#44;3&#37;&#41; en pacientes trasplantados&#44; frente 32 de las 60 muestras &#40;53&#44;3&#37;&#41; en pacientes inmunocompetentes&#44; siendo estas diferencias significativas &#40;OR ajustada 3&#44;4 &#91;1&#44;2-9&#44;6&#93;&#41;&#46; Al comparar los distintos g&#233;neros de VPH el m&#225;s prevalente fue el VPH-&#946;&#44; aunque no encontramos diferencias significativas en la prevalencia de VPH entre pacientes inmunodeprimidos e inmunocompetentes &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">tabla 3</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Virus del papiloma humano en piel tumoral y piel sana perilesional</span><p id="par0070" class="elsevierStylePara elsevierViewall">Se detect&#243; ADN del VPH con mayor frecuencia en piel sana perilesional que en piel tumoral&#44; tanto en pacientes inmunodeprimidos como en inmunocompetentes&#46; Al comparar los distintos g&#233;neros de VPH entre piel tumoral y piel sana perilesional el g&#233;nero VPH-&#946;&#44; en concreto la especie &#946;-1 fue el m&#225;s prevalente&#44; pero no se encontraron diferencias entre los grupos&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">La <a class="elsevierStyleCrossRef" href="#tbl0020">tabla 4</a> muestra las tasas de detecci&#243;n de ADN del VPH y OR ajustada para las muestras de los pacientes inmunodeprimidos &#40;lesi&#243;n y perilesi&#243;n&#41; y pacientes inmunocompetentes &#40;lesi&#243;n y perilesi&#243;n&#41;&#46; Ajustamos la OR al fototipo&#44; exposici&#243;n solar y localizaci&#243;n de la muestra&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Tipos de virus del papiloma humano</span><p id="par0080" class="elsevierStylePara elsevierViewall">Los tipos VPH del g&#233;nero &#946; fueron los m&#225;s frecuentes&#44; encontr&#225;ndose en 34&#47;60 &#40;56&#44;5&#37;&#41; de las muestras de pacientes inmunodeprimidos y en 26&#47;60 &#40;43&#44;3&#37;&#41; de las muestras de pacientes inmunocompetentes&#46; Dentro del g&#233;nero VPH-&#946; la especie VPH-&#946;1 fue la m&#225;s prevalente&#44; siendo el tipo m&#225;s frecuente el VPH-20&#44; aunque sin encontrarse diferencias significativas entre los grupos&#46; Solo detectamos una muestra de VPH-&#945; en un paciente inmunocompetente&#46; VPH-&#947; mostr&#243; una fuerte asociaci&#243;n a pacientes inmunodeprimidos&#44; aunque sin alcanzar significaci&#243;n estad&#237;stica&#46; En 6 determinaciones la PCR para VPH fue positiva de forma d&#233;bil&#44; no pudi&#233;ndose secuenciar al tener poca cantidad de ADN viral&#46; Se detectaron 4 muestras de VPH no clasificados en Genbank &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">tabla 4</a>&#41;&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">Se detectaron infecciones mixtas &#40;por m&#250;ltiples tipos de VPH&#41; en 29 de las 120 determinaciones&#44; siendo m&#225;s frecuentes en pacientes inmunodeprimidos &#40;17&#47;60&#41; que en inmunocompetentes &#40;12&#47;60&#41;&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Factores de riesgo</span><p id="par0090" class="elsevierStylePara elsevierViewall">Los pacientes inmunodeprimidos e inmunocompetentes fueron similares en edad y sexo&#46; Tampoco difirieron significativamente con respecto a la exposici&#243;n solar&#44; localizaci&#243;n del tumor&#44; fotototipo o historia de verrugas o queratosis act&#237;nicas&#46; La localizaci&#243;n del tumor en &#225;reas fotoexpuestas fue la &#250;nica variable asociada de forma significativa a un mayor riesgo de VPH en pacientes inmunodeprimidos&#46; En pacientes inmunocompetentes la exposici&#243;n ocupacional alta&#44; la localizaci&#243;n en &#225;reas expuestas y el fototipo bajo fueron significativamente m&#225;s frecuentes en los pacientes positivos para el VPH&#46; En pacientes inmunodeprimidos el riesgo de positividad del VPH tambi&#233;n fue mayor en pacientes con queratosis act&#237;nicas y verrugas&#44; pero las diferencias no fueron estad&#237;sticamente significativas &#40;<a class="elsevierStyleCrossRef" href="#tbl0025">tabla 5</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0025"></elsevierMultimedia></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Virus del papiloma humano en piel tumoral</span><p id="par0095" class="elsevierStylePara elsevierViewall">Recogimos las muestras de 60 lesiones tumorales&#58; 30 de pacientes inmunodeprimidos &#40;7 CEC&#44; 10 CEC <span class="elsevierStyleItalic">in situ</span> y 13 CBC&#41; y 30 de pacientes inmunocompetentes &#40;7 CEC&#44; 10 CEC <span class="elsevierStyleItalic">in situ</span> y 13 CBC&#41;&#46; La presencia de VPH fue m&#225;s frecuente en CEC <span class="elsevierStyleItalic">in situ</span> tanto en pacientes inmunodeprimidos como en inmunocompetentes&#44; detect&#225;ndose en 8&#47;10 &#40;80&#37;&#41; de los CEC <span class="elsevierStyleItalic">in situ</span> en pacientes inmunodeprimidos y en 6&#47;10 &#40;60&#37;&#41; de los CEC <span class="elsevierStyleItalic">in situ</span> de los pacientes inmunocompetentes&#46; La menor prevalencia de VPH la encontramos en los CBC&#44; tanto en inmunodeprimidos como en inmunocompetentes&#44; aunque estos resultados no alcanzaron significaci&#243;n estad&#237;stica &#40;<a class="elsevierStyleCrossRef" href="#tbl0030">tabla 6</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0030"></elsevierMultimedia></span></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Discusi&#243;n</span><p id="par0100" class="elsevierStylePara elsevierViewall">En este estudio se ha examinado una poblaci&#243;n de pacientes inmunodeprimidos e inmunocompetentes para identificar la prevalencia y el espectro de los tipos de VPH presentes en el tejido tumoral y en la piel sana perilesional&#46; La mayor prevalencia de VPH encontrada en pacientes inmunodeprimidos frente inmunocompetentes concuerda con otros art&#237;culos publicados previamente&#46; En el estudio de Harwood et al&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> se compara por la t&#233;cnica de PCR degenerada la prevalencia de VPH en 148 muestras&#58; 85 muestras de pacientes inmunodeprimidos &#40;44 CEC&#44; 24 CBC y 17 lesiones premalignas&#58; queratosis act&#237;nicas o CEC <span class="elsevierStyleItalic">in situ</span>&#41; y 63 de pacientes inmunocompetentes &#40;22 CEC&#44; 30 CBC y 11 lesiones premalignas&#41; encontrando una mayor prevalencia de VPH en las lesiones de los pacientes inmunodeprimidos en comparaci&#243;n con los pacientes inmunocompetentes &#40;82 frente 36&#37;&#59; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">Al comparar la prevalencia de VPH entre piel tumoral y piel sana perilesional la presencia de VPH ha sido mayor en piel sana perilesional que en piel tumoral&#44; tanto en pacientes inmunodeprimidos como en inmunocompetentes&#44; aunque estos resultados no han alcanzado significaci&#243;n estad&#237;stica&#46; La alta prevalencia de ADN del VPH en piel sana perilesional&#44; tanto en pacientes inmunodeprimidos como en inmunocompetentes&#44; concuerda con los hallazgos de estudios anteriores que sugieren que el ADN del VPH se encuentra ampliamente distribuido en la piel de la poblaci&#243;n general<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">18&#44;19</span></a>&#46; Estudios realizados en personas inmunocompetentes han encontrado ADN del VPH en 67-74&#37; de los pelos arrancados<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">19&#44;20</span></a> y en el 69-80&#37; de los frotis de piel<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a>&#46; Estos estudios&#44; junto con nuestros datos&#44; sugieren que la presencia de ADN de VPH es generalizada en piel de apariencia normal&#46; En otros estudios&#44; en cambio&#44; se detect&#243; ADN del VPH con mayor frecuencia en piel tumoral que en piel sana&#46; En el estudio de Forslund et al&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> se compar&#243; la presencia de VPH en CCNM&#44; queratosis act&#237;nicas y piel sana del mismo paciente&#44; hall&#225;ndose una prevalencia de VPH mayor en la piel tumoral que en la piel sana&#44; y llegaron a la conclusi&#243;n que la especie VPH-&#946;2 se asociaba a CEC&#46; En nuestro estudio no determinamos la presencia de VPH en queratosis act&#237;nicas y la mayor&#237;a de tumores incluidos fueron CBC&#46; En este punto debemos puntualizar que la mayor&#237;a de trabajos relacionan la infecci&#243;n del VPH con el CEC<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a>&#46; Los trabajos que intentan buscar una asociaci&#243;n entre infecci&#243;n por VPH y CBC son menores<a class="elsevierStyleCrossRefs" href="#bib0120"><span class="elsevierStyleSup">24&#44;25</span></a>&#44; y la gran mayor&#237;a no encuentran una asociaci&#243;n estad&#237;sticamente significativa&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">No hemos encontrado diferencias significativas en el espectro de tipos de VPH entre las 2 poblaciones&#44; si bien el g&#233;nero VPH-&#946; fue el m&#225;s prevalente&#44; sobre todo la especie VPH-&#946;1&#46; Datos similares se muestran en otros art&#237;culos<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a>&#44; aunque muchos de estos trabajos se basan en la clasificaci&#243;n taxon&#243;mica cl&#225;sica de VPH en&#58; mucosos&#44; cut&#225;neos o asociados a epidermodisplasia verruciforme &#40;EV&#41;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a>&#46; Seg&#250;n la clasificaci&#243;n de Villiers de 2004<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> &#40;que clasifica los VPH en 16 g&#233;neros&#41; los tipos anteriormente clasificados como VPH-EV ahora se incluyen en el g&#233;nero &#946;&#58; VPH-&#946;1 y VPH-&#946;2&#46; En el estudio de Asgari et al&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> la especie m&#225;s prevalente fue VPH-&#946;2&#44; aunque en este estudio&#44; como en el nuestro&#44; el tipo m&#225;s frecuente detectado fue el VPH-20 &#40;perteneciente a VPH-&#946;1&#41;&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">Las muestras de &#225;reas fotoexpuestas mostraron mayor prevalencia de ADN del VPH tanto en pacientes inmunodeprimidos como en inmunocompetentes&#46; Nuestro estudio apoya la teor&#237;a de la importante interacci&#243;n de la luz UV y la presencia de VPH&#46; La radiaci&#243;n UV tambi&#233;n se asoci&#243; con CCNM en pacientes VPH-<span class="elsevierStyleItalic">beta</span> positivos en el estudio de Bouwes Bavinck et al&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a>&#46; Al estudiar los posibles factores de confusi&#243;n solo la localizaci&#243;n del tumor en &#225;reas fotoexpuestas se asoci&#243; con un mayor riesgo de VPH en pacientes inmunodeprimidos&#46; En pacientes inmunocompetentes la exposici&#243;n solar ocupacional alta&#44; la localizaci&#243;n del tumor en &#225;reas fotoexpuestas y el fototipo bajo tambi&#233;n se asociaron con un mayor riesgo de VPH de forma significativa&#46; El importante papel de la radiaci&#243;n UV tambi&#233;n se refleja en otros trabajos como el de Forslund et al&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a>&#44; donde el ADN del VPH tambi&#233;n se asoci&#243; de forma significativa con la exposici&#243;n al sol&#44; tanto en piel tumoral como en piel sana&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">Al comparar la presencia de VPH en las muestras tumorales la presencia de VPH fue mayor en los CEC <span class="elsevierStyleItalic">in situ</span> que en los CEC o CBC&#44; tanto en pacientes inmunodeprimidos como inmunocompetentes&#46; Este hallazgo coincide con los estudios que sostienen la teor&#237;a de que el VPH en el c&#225;ncer de piel se detecta con mayor frecuencia en las lesiones m&#225;s precoces como los CEC <span class="elsevierStyleItalic">in situ</span> y queratosis con displasia&#44; sugiriendo que la influencia del VPH se centrar&#237;a fundamentalmente en las etapas iniciales de la carcinog&#233;nesis cut&#225;nea&#44; m&#225;s que en la perpetuaci&#243;n tumoral<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">29&#44;30</span></a>&#46; En nuestro trabajo&#44; si bien no determinamos la presencia de VPH en queratosis act&#237;nicas&#44; la presencia de queratosis act&#237;nicas o verrugas se asoci&#243; a mayor riesgo de VPH en pacientes inmunodeprimidos&#44; aunque estos resultados no alcanzaron significaci&#243;n estad&#237;stica&#44; seguramente por el tama&#241;o muestral limitado&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">Los datos obtenidos en este estudio ponen de relieve las diferencias potencialmente importantes en la prevalencia de VPH de pacientes inmunodeprimidos e inmunocompetentes&#44; apoyando la compleja interacci&#243;n entre VPH&#44; la exposici&#243;n a la radiaci&#243;n UV y el estado de inmunosupresi&#243;n&#46; La mayor prevalencia de VPH encontrada en piel sana perilesional sugiere que el ADN del VPH se encuentra ampliamente distribuido en la poblaci&#243;n general&#46; Si bien no hemos encontrado correlaci&#243;n entre la presencia de VPH y el c&#225;ncer de piel hemos de tener en cuenta que se trata de una serie peque&#241;a&#44; de car&#225;cter informativo y que se necesitan estudios m&#225;s amplios para valorar la implicaci&#243;n del VPH en el c&#225;ncer de piel&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Responsabilidades &#233;ticas</span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Protecci&#243;n de personas y animales</span><p id="par0130" class="elsevierStylePara elsevierViewall">Los autores declaran que para esta investigaci&#243;n no se han realizado experimentos en seres humanos ni en animales&#46;</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Confidencialidad de los datos</span><p id="par0135" class="elsevierStylePara elsevierViewall">Los autores declaran que han seguido los protocolos de su centro de trabajo sobre la publicaci&#243;n de datos de pacientes y que todos los pacientes incluidos en el estudio han recibido informaci&#243;n suficiente y han dado su consentimiento informado por escrito para participar en dicho estudio&#46;</p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0155">Derecho a la privacidad y consentimiento informado</span><p id="par0140" class="elsevierStylePara elsevierViewall">Los autores declaran que en este art&#237;culo no aparecen datos de pacientes&#46;</p></span></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0160">Conflicto de intereses</span><p id="par0145" class="elsevierStylePara elsevierViewall">Los autores declaran que no tienen ning&#250;n conflicto de intereses</p></span></span>"
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        "resumen" => "<span class="elsevierStyleSectionTitle" id="sect0010">Antecedentes</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">La influencia del virus del papiloma humano &#40;VPH&#41; en el desarrollo de carcinoma cut&#225;neo no melanoma es un tema controvertido&#46; VPH-&#946; es el g&#233;nero m&#225;s frecuente relacionado con el desarrollo de c&#225;ncer de piel&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0015">Objetivos</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Analizar la prevalencia y espectro de los tipos de VPH presentes en piel tumoral y piel sana perilesional en pacientes inmunodeprimidos y pacientes inmunocompetentes&#44; as&#237; como evaluar la influencia de diferentes factores cl&#237;nicos en la prevalencia del VPH en c&#225;ncer de piel&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0020">M&#233;todos</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Se determin&#243; la presencia de VPH en 120 muestras mediante PCR <span class="elsevierStyleItalic">nested</span> y posterior secuenciaci&#243;n&#46; Se tom&#243; biopsia de piel de 30 pacientes trasplantados renales y de 30 pacientes inmunocompetentes con c&#225;ncer cut&#225;neo tanto de zona tumoral como de piel sana perilesional&#46; Se registraron las variables potenciales de confusi&#243;n&#46; Los datos fueron analizados utilizando an&#225;lisis de regresi&#243;n log&#237;stica multivariado&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0025">Resultados</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">ADN del VPH fue detectado en 44&#47;60 &#40;73&#44;3&#37;&#41; de las muestras de pacientes inmunodeprimidos y en 32&#47;60 &#40;53&#44;3&#37;&#41; de las muestras de pacientes inmunocompetentes &#40;OR ajustada 3&#44;4 &#91;1&#44;2-9&#44;6&#93;&#41;&#46; Al comparar la presencia de VPH en los 2 grupos entre piel tumoral y piel sana perilesional la presencia de VPH en piel sana perilesional fue mayor que en piel tumoral&#46; El g&#233;nero m&#225;s frecuente aislado fue el VPH-&#946;&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0030">Conclusi&#243;n</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Un amplio espectro de tipos de VPH&#44; la mayor&#237;a del g&#233;nero &#946;&#44; se encuentran en la piel de pacientes trasplantados e inmunocompetentes con c&#225;ncer cut&#225;neo&#46;</p>"
      ]
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span class="elsevierStyleSectionTitle" id="sect0040">Background</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">The influence of human papillomavirus &#40;HPV&#41; on the development of nonmelanoma skin cancer &#40;NMSC&#41; is a topic of debate&#46; HPV types from the beta genus &#40;HPV-&#946;&#41; have been most frequently associated with the development of skin cancer&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0045">Objectives</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">To analyze the prevalence and range of HPV types in NMSC lesions and healthy perilesional skin in immunodepressed and immunocompetent patients and to evaluate the influence of various clinical factors on the prevalence of HPV in skin cancer&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0050">Methods</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Nested polymerase chain reaction and sequencing were used to detect HPV in 120 NMSC samples obtained by biopsy from 30 kidney transplant recipients and 30 immunocompetent patients&#46; In all cases&#44; a sample was taken from the tumor site and the surrounding healthy skin&#46; Potential confounders were assessed and the data analyzed by multivariate logistic regression&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0055">Results</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">HPV DNA was detected in 44 &#40;73&#46;3&#37;&#41; of the 60 samples from immunodepressed patients and in 32 &#40;53&#46;3&#37;&#41; of the 60 samples from immunocompetent patients &#40;adjusted odds ratio&#44; 3&#46;4&#59; 95&#37; <span class="elsevierStyleSmallCaps">CI</span>&#44; 1&#46;2-9&#46;6&#41;&#46; In both groups of patients&#44; HPV was more common in healthy perilesional skin than in lesional skin&#46; HPV-&#946; was the most common type isolated&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0060">Conclusion</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">We found a wide range of HPV types &#40;mostly HPV-&#946;&#41; in the skin of kidney transplant recipients and immunocompetent patients with skin cancer&#46;</p>"
      ]
    ]
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          "es" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">1&#58; lesi&#243;n tumoral&#59; 2&#58; piel sana perilesional&#46;</p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td 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" style="border-bottom: 2px solid black">G&#233;nero&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Especie&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">Tipo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">Otros tipos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">Comentarios&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></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  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Beta&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">VPH-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">VPH-8&#44; 12&#44; 14&#44; 19&#44; 20&#44; 21&#44; 25&#44; 36&#44; 47&#44; 93&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Lesiones cut&#225;neas&#46; Com&#250;nmente asociado a lesiones en epidermodisplasia verruciforme &#40;EV&#41; o pacientes inmunodeprimidos&#46;Normalmente lesiones benignas&#44; pero tambi&#233;n asociado a lesiones malignas&#44; incluso en pacientes inmunocompetentes&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">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">VPH-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">VPH-15&#44; 17&#44; 22&#44; 23&#44; 37&#44; 38&#44; 80&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Lesiones cut&#225;neas&#46; Com&#250;nmente asociado a lesiones en EV o pacientes inmunodeprimidos&#46;Normalmente lesiones benignas&#44; pero tambi&#233;n asociado a lesiones malignas&#44; incluso en pacientes inmunocompetentes&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">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">VPH-49&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">VPH-75&#44; 76&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Lesiones cut&#225;neas benignas&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">VPHcand92&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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">Lesiones cut&#225;neas premalignas y malignas&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">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">VPHcand96&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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">Lesiones cut&#225;neas premalignas y malignas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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          "es" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Clasificaci&#243;n taxon&#243;mica del virus del papiloma humano &#40;VPH&#41; del g&#233;nero beta</p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">Pacientes inmunodeprimidos &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>30&#41;N&#46;<span class="elsevierStyleSup">o</span>&#47;total &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">Pacientes inmunocompetentes &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>30&#41;N&#46;<span class="elsevierStyleSup">o</span>&#47;total &#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-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">p-valor&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"><span class="elsevierStyleItalic">Edad-a&#241;os &#40;media</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#177;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">DE&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">69&#44;57<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>7&#44;61&nbsp;\t\t\t\t\t\t\n
                  \t\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">72&#44;53<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>12&#44;57&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="char" valign="\n
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                  \t\t\t\t">0&#44;247&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t">14&#47;30 &#40;46&#44;6&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">16&#47;30 &#40;53&#44;3&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#44;605&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Var&#243;n&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">16&#47;30 &#40;53&#44;3&#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">14&#47;30 &#40;46&#44;6&#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">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">&#946;-papiloma virus</span></td></tr><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Todos VPH-&#946;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Beta- 1&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Beta-2&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Beta- 3&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Beta- 4&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Beta- 5&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">&#947;-papiloma virus</span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\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="elsevierStyleHsp" style=""></span>Todos VPH-&#947;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">3 &#40;10&#44;0&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">2 &#40;6&#44;7&#41;&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"><span class="elsevierStyleHsp" style=""></span>VPH-1&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1 &#40;3&#44;3&#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
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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
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>VPH-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="char" valign="\n
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                  \t\t\t\t">1 &#40;3&#44;3&#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
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t\ttop\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
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>VPH-10&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">1 &#40;3&#44;3&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" 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</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\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="char" valign="\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="7" align="left" valign="\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"><span class="elsevierStyleItalic">No clasificable VPH</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  """
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Zona no fotoexpuesta&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Zona fotoexpuesta&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " colspan="9" align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Queratosis act&#237;nicas</span></td></tr><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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ISSN: 00017310
Idioma original: Español
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