array:23 [
  "pii" => "S1578219008702506"
  "issn" => "15782190"
  "doi" => "10.1016/S1578-2190(08)70250-6"
  "estado" => "S300"
  "fechaPublicacion" => "2008-05-01"
  "aid" => "70250"
  "copyright" => "Academia Española de Dermatología y Venereología and Elsevier España, S.L."
  "copyrightAnyo" => "2008"
  "documento" => "article"
  "crossmark" => 0
  "subdocumento" => "fla"
  "cita" => "Actas Dermosifiliogr. 2008;99:269-74"
  "abierto" => array:3 [
    "ES" => true
    "ES2" => true
    "LATM" => true
  ]
  "gratuito" => true
  "lecturas" => array:2 [
    "total" => 2401
    "formatos" => array:3 [
      "EPUB" => 36
      "HTML" => 1439
      "PDF" => 926
    ]
  ]
  "itemSiguiente" => array:18 [
    "pii" => "S1578219008702518"
    "issn" => "15782190"
    "doi" => "10.1016/S1578-2190(08)70251-8"
    "estado" => "S300"
    "fechaPublicacion" => "2008-05-01"
    "aid" => "70251"
    "copyright" => "Academia Española de Dermatología y Venereología and Elsevier España, S.L."
    "documento" => "article"
    "crossmark" => 0
    "subdocumento" => "fla"
    "cita" => "Actas Dermosifiliogr. 2008;99:275-80"
    "abierto" => array:3 [
      "ES" => true
      "ES2" => true
      "LATM" => true
    ]
    "gratuito" => true
    "lecturas" => array:2 [
      "total" => 2329
      "formatos" => array:3 [
        "EPUB" => 32
        "HTML" => 1543
        "PDF" => 754
      ]
    ]
    "en" => array:11 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Original articles</span>"
      "titulo" => "Mohs Micrographic Surgery&#58; Our First 100 Patients"
      "tienePdf" => "en"
      "tieneTextoCompleto" => 0
      "tieneResumen" => array:2 [
        0 => "en"
        1 => "es"
      ]
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "275"
          "paginaFinal" => "280"
        ]
      ]
      "titulosAlternativos" => array:1 [
        "es" => array:1 [
          "titulo" => "Cirug&#237;a de Mohs&#58; Nuestros Primeros Cien Pacientes"
        ]
      ]
      "contieneResumen" => array:2 [
        "en" => true
        "es" => true
      ]
      "contienePdf" => array:1 [
        "en" => true
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "T&#46; Alonso, P&#46; S&#225;nchez, A&#46; Gonz&#225;lez, J&#46; Ingelmo, I&#46; Ruiz, S&#46; Delgado, M&#46;A&#46; Rodr&#237;guez"
          "autores" => array:7 [
            0 => array:2 [
              "nombre" => "T&#46;"
              "apellidos" => "Alonso"
            ]
            1 => array:2 [
              "nombre" => "P&#46;"
              "apellidos" => "S&#225;nchez"
            ]
            2 => array:2 [
              "nombre" => "A&#46;"
              "apellidos" => "Gonz&#225;lez"
            ]
            3 => array:2 [
              "nombre" => "J&#46;"
              "apellidos" => "Ingelmo"
            ]
            4 => array:2 [
              "nombre" => "I&#46;"
              "apellidos" => "Ruiz"
            ]
            5 => array:2 [
              "nombre" => "S&#46;"
              "apellidos" => "Delgado"
            ]
            6 => array:2 [
              "nombre" => "M&#46;A&#46;"
              "apellidos" => "Rodr&#237;guez"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "en"
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1578219008702518?idApp=UINPBA000044"
    "url" => "/15782190/0000009900000004/v1_201304241431/S1578219008702518/v1_201304241431/en/main.assets"
  ]
  "itemAnterior" => array:18 [
    "pii" => "S157821900870249X"
    "issn" => "15782190"
    "doi" => "10.1016/S1578-2190(08)70249-X"
    "estado" => "S300"
    "fechaPublicacion" => "2008-05-01"
    "aid" => "70249"
    "copyright" => "Academia Espa&#241;ola de Dermatolog&#237;a y Venereolog&#237;a and Elsevier Espa&#241;a&#44; S&#46;L&#46;"
    "documento" => "article"
    "crossmark" => 0
    "subdocumento" => "fla"
    "cita" => "Actas Dermosifiliogr. 2008;99:262-8"
    "abierto" => array:3 [
      "ES" => true
      "ES2" => true
      "LATM" => true
    ]
    "gratuito" => true
    "lecturas" => array:2 [
      "total" => 3512
      "formatos" => array:3 [
        "EPUB" => 32
        "HTML" => 1547
        "PDF" => 1933
      ]
    ]
    "en" => array:11 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Advances in dermatology</span>"
      "titulo" => "Recent Advances in Laser Therapy and Other Technologies"
      "tienePdf" => "en"
      "tieneTextoCompleto" => 0
      "tieneResumen" => array:2 [
        0 => "en"
        1 => "es"
      ]
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "262"
          "paginaFinal" => "268"
        ]
      ]
      "titulosAlternativos" => array:1 [
        "es" => array:1 [
          "titulo" => "Recientes Avances en L&#225;ser y Otras Tecnolog&#237;as"
        ]
      ]
      "contieneResumen" => array:2 [
        "en" => true
        "es" => true
      ]
      "contienePdf" => array:1 [
        "en" => true
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "P&#46; Boixeda, M&#46; Calvo, L&#46; Bagazgoitia"
          "autores" => array:3 [
            0 => array:2 [
              "nombre" => "P&#46;"
              "apellidos" => "Boixeda"
            ]
            1 => array:2 [
              "nombre" => "M&#46;"
              "apellidos" => "Calvo"
            ]
            2 => array:2 [
              "nombre" => "L&#46;"
              "apellidos" => "Bagazgoitia"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "en"
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S157821900870249X?idApp=UINPBA000044"
    "url" => "/15782190/0000009900000004/v1_201304241431/S157821900870249X/v1_201304241431/en/main.assets"
  ]
  "en" => array:15 [
    "idiomaDefecto" => true
    "cabecera" => "<span class="elsevierStyleTextfn">Original articles</span>"
    "titulo" => "Epidermodysplasia Verruciformis-Like Cells as Histologic Markers of Immunosuppression&#58; Review of 229 Squamous Cell Carcinomas<a class="elsevierStyleCrossRef" href="#fn1"><span class="elsevierStyleSup">&#42;</span></a>"
    "tieneTextoCompleto" => 0
    "paginas" => array:1 [
      0 => array:2 [
        "paginaInicial" => "269"
        "paginaFinal" => "274"
      ]
    ]
    "autores" => array:1 [
      0 => array:4 [
        "autoresLista" => "R&#46; Corbal&#225;n-V&#233;lez, J&#46;A&#46; Ruiz-Maci&#225;, C&#46; Brufau, J&#46;M&#46; L&#243;pez-Lozano, E&#46; Mart&#237;nez-Barba, J&#46; Mart&#237;nez-Escribano, F&#46;J&#46; Carapeto"
        "autores" => array:7 [
          0 => array:4 [
            "nombre" => "R&#46;"
            "apellidos" => "Corbal&#225;n-V&#233;lez"
            "email" => array:1 [
              0 => "raulcorb&#64;gmail&#46;com"
            ]
            "referencia" => array:2 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff1"
              ]
              1 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">¿</span>"
                "identificador" => "cor1"
              ]
            ]
          ]
          1 => array:3 [
            "nombre" => "J&#46;A&#46;"
            "apellidos" => "Ruiz-Maci&#225;"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">b</span>"
                "identificador" => "aff2"
              ]
            ]
          ]
          2 => array:3 [
            "nombre" => "C&#46;"
            "apellidos" => "Brufau"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">c</span>"
                "identificador" => "aff3"
              ]
            ]
          ]
          3 => array:3 [
            "nombre" => "J&#46;M&#46;"
            "apellidos" => "L&#243;pez-Lozano"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">d</span>"
                "identificador" => "aff4"
              ]
            ]
          ]
          4 => array:3 [
            "nombre" => "E&#46;"
            "apellidos" => "Mart&#237;nez-Barba"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">e</span>"
                "identificador" => "aff5"
              ]
            ]
          ]
          5 => array:3 [
            "nombre" => "J&#46;"
            "apellidos" => "Mart&#237;nez-Escribano"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff1"
              ]
            ]
          ]
          6 => array:3 [
            "nombre" => "F&#46;J&#46;"
            "apellidos" => "Carapeto"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">f</span>"
                "identificador" => "aff6"
              ]
            ]
          ]
        ]
        "afiliaciones" => array:6 [
          0 => array:3 [
            "entidad" => "Servicio de Dermatolog&#237;a&#44; Hospital Universitario Virgen de la Arrixaca&#44; Murcia&#44; Spain"
            "etiqueta" => "<span class="elsevierStyleSup">a</span>"
            "identificador" => "aff1"
          ]
          1 => array:3 [
            "entidad" => "Servicio de Anatom&#237;a Patol&#243;gica&#44; Hospital Vega Baja&#44; Orihuela&#44; Alicante&#44; Spain"
            "etiqueta" => "<span class="elsevierStyleSup">b</span>"
            "identificador" => "aff2"
          ]
          2 => array:3 [
            "entidad" => "Servicio de Dermatolog&#237;a&#44; Hospital General Reina Sof&#237;a&#44; Murcia&#44; Spain"
            "etiqueta" => "<span class="elsevierStyleSup">c</span>"
            "identificador" => "aff3"
          ]
          3 => array:3 [
            "entidad" => "Servicio de Medicina Preventiva&#44; Hospital Vega Baja&#44; Orihuela&#44; Alicante&#44; Spain"
            "etiqueta" => "<span class="elsevierStyleSup">d</span>"
            "identificador" => "aff4"
          ]
          4 => array:3 [
            "entidad" => "Servicio de Anatom&#237;a Patol&#243;gica&#44; Hospital Universitario Virgen de la Arrixaca&#44; Murcia&#44; Spain"
            "etiqueta" => "<span class="elsevierStyleSup">e</span>"
            "identificador" => "aff5"
          ]
          5 => array:3 [
            "entidad" => "Servicio de Dermatolog&#237;a&#44; Hospital Cl&#237;nico Universitario Lozano Blesa&#44; Zaragoza&#44; Spain<a class="elsevierStyleCrossRef" href="#fn1"><span class="elsevierStyleSup">&#42;</span></a>"
            "etiqueta" => "<span class="elsevierStyleSup">f</span>"
            "identificador" => "aff6"
          ]
        ]
        "correspondencia" => array:1 [
          0 => array:3 [
            "identificador" => "cor1"
            "etiqueta" => "&#8270;"
            "correspondencia" => "Correspondence&#58; Servicio de Dermatolog&#237;a&#44; Hospital Universitario Virgen de la Arrixaca&#44; Ctra&#46; Murcia-Cartagena&#44; s&#47;n&#44; 30120 El Palmar&#44; Murcia&#44; Spain&#46;"
          ]
        ]
      ]
    ]
    "titulosAlternativos" => array:1 [
      "es" => array:1 [
        "titulo" => "Las C&#233;lulas Tipo Epidermodisplasia Verruciforme Como Marcador Histol&#243;gico de Inmunodepresi&#243;n&#58; Revisi&#243;n de 229 Carcinomas Espinocelulares"
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaAceptado" => "2007-09-11"
    "PalabrasClave" => array:2 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Key words"
          "identificador" => "xpalclavsec84166"
          "palabras" => array:4 [
            0 => "epidermodysplasia verruciformis"
            1 => "immunosuppression"
            2 => "papillomavirus"
            3 => "solar elastosis"
          ]
        ]
      ]
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec84165"
          "palabras" => array:4 [
            0 => "epidermodisplasia verruciforme"
            1 => "inmunodepresi&#243;n"
            2 => "papilomavirus"
            3 => "elastosis solar"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span class="elsevierStyleSectionTitle">Introduction</span><p class="elsevierStyleSimplePara elsevierViewall">Epidermodysplasia verruciformis &#40;EV&#41; is associated with greater susceptibility to infection by certain oncogenic subtypes of human papillomavirus &#40;HPV&#41;&#46; Among other histologic findings&#44; large&#44; clear&#44; oval or rounded cells &#40;EV cells&#41; are observed in the granular layer in EV&#44; and some authors consider these cells to be markers of immunosuppression&#46;</p> <span class="elsevierStyleSectionTitle">Material and Methods</span><p class="elsevierStyleSimplePara elsevierViewall">We analyzed 229 squamous cell carcinomas &#40;SCC&#41; to determine whether EV cells were present and to assess whether their presence was associated either with localized or cutaneous immunosuppression &#40;tumors with signs of severe chronic actinic damage or severe stasis dermatitis&#41; or with systemic immunosuppression &#40;immunocompromised or elderly patients&#41;&#46;</p> <span class="elsevierStyleSectionTitle">Results</span><p class="elsevierStyleSimplePara elsevierViewall">We observed EV cells in 33 SCC&#46; No statistically significant relationship was observed between the presence of EV cells and immunosuppression&#46; We performed polymerase chain reaction in 8 lesions&#44; but the results were not informative as the DNA was denatured&#46;</p> <span class="elsevierStyleSectionTitle">Conclusions</span><p class="elsevierStyleSimplePara elsevierViewall">We found no relationship between the presence of EV cells and localized or systemic immunosuppression&#44; possibly because the sample was inadequate &#40;almost all SCC studied were associated with signs of immunosuppression&#44; irrespective of the presence or absence of EV cells&#41;&#46; Further studies will be required to compare lesions associated with immunosuppression with those in which immunosuppression is absent&#46; The presence of EV cells may be the result of cytopathic effects of certain HPV subtypes&#44; such as HPV 5 or 8&#44; but this will need to be demonstrated using techniques such as polymerase chain reaction&#46;</p>"
      ]
      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<span class="elsevierStyleSectionTitle">Introducci&#243;n</span><p class="elsevierStyleSimplePara elsevierViewall">La epidermodisplasia verruciforme &#40;EV&#41; es una enfermedad en la que existe una mayor susceptibilidad gen&#233;tica a la infecci&#243;n por determinados subtipos oncog&#233;nicos del virus del papiloma humano &#40;VPH&#41;&#46; Entre otros hallazgos histol&#243;gicos&#44; en la EV suelen observarse unas c&#233;lulas claras&#44; grandes&#44; ovaladas o redondeadas &#40;c&#233;lulas EV&#41; en la capa granulosa&#44; que seg&#250;n algunos autores se podr&#237;an considerar como un marcador histol&#243;gico de inmunodepresi&#243;n&#46;</p> <span class="elsevierStyleSectionTitle">Material y m&#233;todos</span><p class="elsevierStyleSimplePara elsevierViewall">Hemos estudiado 229 carcinomas espinocelulares &#40;CE&#41; para valorar si presentaban c&#233;lulas EV y si se relacionaban con inmunodepresi&#243;n&#44; tanto localizada o cut&#225;nea &#40;tumores con signos de intenso da&#241;o solar cr&#243;nico o con una dermatitis de estasis intensa&#41;&#44; como sist&#233;mica &#40;pacientes inmunodeprimidos o ancianos&#41;&#46;</p> <span class="elsevierStyleSectionTitle">Resultados</span><p class="elsevierStyleSimplePara elsevierViewall">Observamos c&#233;lulas EV en 33 carcinomas&#46; No hemos encontrado relaci&#243;n significativa entre la existencia de c&#233;lulas EV e inmunodepresi&#243;n&#46; Realizamos reacci&#243;n en cadena de la polimerasa &#40;PCR&#41; en 8 lesiones&#44; pero los resultados no fueron valorables porque el ADN estaba desnaturalizado&#46;</p> <span class="elsevierStyleSectionTitle">Conclusiones</span><p class="elsevierStyleSimplePara elsevierViewall">No hemos demostrado relaci&#243;n entre las c&#233;lulas EV e inmunodepresi&#243;n&#44; localizada o sist&#233;mica&#44; posiblemente porque la muestra no era adecuada &#40;se podr&#237;a considerar que pr&#225;cticamente todos los CE estudiados se asociaban a signos de inmunodepresi&#243;n&#44; tanto aquellos que presentaban c&#233;lulas EV como los que no&#41;&#46; Ser&#237;an necesarios m&#225;s estudios que comparasen lesiones asociadas a inmunodepresi&#243;n con otras que no&#46; Es posible que estas c&#233;lulas EV sean el resultado de los efectos citop&#225;ticos de determinados subtipos de VPH&#44; como el VPH-5 o el VPH-8&#44; aunque ser&#237;a necesario demostrar esta hip&#243;tesis mediante t&#233;cnicas de PCR o similar&#46;</p>"
      ]
    ]
    "NotaPie" => array:1 [
      0 => array:2 [
        "etiqueta" => "&#42;"
        "nota" => "<p class="elsevierStyleNotepara">2006 August C&#46; Stiefel Award&#46;</p>"
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:1 [
          "bibliografiaReferencia" => array:27 [
            0 => array:3 [
              "identificador" => "bib1"
              "etiqueta" => "1&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Epidermodysplasia verruciformis as a model of Human Papillomavirus-inducel genetic cancer of the skin"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "S&#46; Majewski"
                            1 => "S&#46; Jablonska"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Arch Dermatol"
                        "fecha" => "1995"
                        "volumen" => "131"
                        "paginaInicial" => "1312"
                        "paginaFinal" => "1318"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7503577"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib2"
              "etiqueta" => "2&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Epidermodisplasia verruciforme"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "V&#46;P&#46; S&#225;nchez-Garc&#237;a"
                            1 => "A&#46; Sanz"
                            2 => "C&#46; Eloy"
                            3 => "A&#46; Vera"
                            4 => "T&#46; Mart&#237;n"
                            5 => "F&#46; S&#225;nchez-Fajardo"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Actas Dermosifiliogr"
                        "fecha" => "2005"
                        "volumen" => "96"
                        "paginaInicial" => "531"
                        "paginaFinal" => "533"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16476290"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib3"
              "etiqueta" => "3&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Clinical aspects of epidermodysplasia verruciformis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "W&#46;R&#46; de Oliveira"
                            1 => "C&#46; Festa Neto"
                            2 => "P&#46;L&#46; Rady"
                            3 => "S&#46;K&#46; Tyring"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Eur Acad Dermatol Venereol"
                        "fecha" => "2003"
                        "volumen" => "17"
                        "paginaInicial" => "394"
                        "paginaFinal" => "398"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12834447"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib4"
              "etiqueta" => "4&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Partial defects of cell-mediated immunity in patients with epidermodysplasia verruciformis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "S&#46; Majewski"
                            1 => "E&#46; Skipinska-Rozewska"
                            2 => "S&#46; Jablonska"
                            3 => "M&#46; Wasik"
                            4 => "J&#46; Misiewicz"
                            5 => "G&#46; Orth"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Am Acad Dermatol"
                        "fecha" => "1986"
                        "volumen" => "15"
                        "paginaInicial" => "966"
                        "paginaFinal" => "973"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/3491095"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib5"
              "etiqueta" => "5&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Natural cell-mediated cytotoxicity against various target cells in patients with epidermodysplasia verruciformis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "S&#46; Majewski"
                            1 => "J&#46; Malejczyk"
                            2 => "S&#46; Jablonska"
                            3 => "J&#46; Misiewicz"
                            4 => "L&#46; Rudnicka"
                            5 => "S&#46; Obalek"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Am Acad Dermatol"
                        "fecha" => "1990"
                        "volumen" => "22"
                        "paginaInicial" => "423"
                        "paginaFinal" => "427"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2155952"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            5 => array:3 [
              "identificador" => "bib6"
              "etiqueta" => "6&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The histologic spectrum of Epidermodysplasia Verruciformis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "G&#46;J&#46; Nuovo"
                            1 => "M&#46; Ishag"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Surg Pathol"
                        "fecha" => "2000"
                        "volumen" => "24"
                        "paginaInicial" => "1400"
                        "paginaFinal" => "1406"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11023102"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            6 => array:3 [
              "identificador" => "bib7"
              "etiqueta" => "7&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Viral diseases"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "D&#46; Weedon"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "LibroEditado" => array:4 [
                        "titulo" => "Skin Pathology"
                        "paginaInicial" => "583"
                        "paginaFinal" => "603"
                        "serieFecha" => "1998"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            7 => array:3 [
              "identificador" => "bib8"
              "etiqueta" => "8&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Skin cancer in organ transplant recipients&#58; Epidemiology&#44; pathogenesis&#44; and management"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "D&#46; Berg"
                            1 => "C&#46;C&#46; Otley"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Am Acad Dermatol"
                        "fecha" => "2002"
                        "volumen" => "47"
                        "paginaInicial" => "1"
                        "paginaFinal" => "17"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12077575"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            8 => array:3 [
              "identificador" => "bib9"
              "etiqueta" => "9&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Shortage of circulating naive CD8 &#63;&#63;T cells provides new insights on immunodeficiency in aging"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "F&#46;F&#46; Fagnoni"
                            1 => "R&#46; Vescovini"
                            2 => "G&#46; Passeri"
                            3 => "G&#46; Bologna"
                            4 => "M&#46; Pedrazzoni"
                            5 => "G&#46; Lavagetto"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Blood"
                        "fecha" => "2000"
                        "volumen" => "95"
                        "paginaInicial" => "2860"
                        "paginaFinal" => "2868"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10779432"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            9 => array:3 [
              "identificador" => "bib10"
              "etiqueta" => "10&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Epidemiolog&#237;a e inmunopatogenia del c&#225;ncer cut&#225;neo no melanoma&#46; El papel iniciador y promotor del VPH"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "V&#46;G&#46; Villarrubia"
                            1 => "L&#46;A&#46; Costa"
                            2 => "M&#46; P&#233;rez"
                            3 => "S&#46; Vidal"
                            4 => "P&#46; Jaen"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Piel"
                        "fecha" => "2001"
                        "volumen" => "16"
                        "paginaInicial" => "428"
                        "paginaFinal" => "438"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            10 => array:3 [
              "identificador" => "bib11"
              "etiqueta" => "11&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Mechanism involved in ultraviolet light-induced immunosuppression"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "F&#46; Aubin"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Eur J Dermatol"
                        "fecha" => "2003"
                        "volumen" => "13"
                        "paginaInicial" => "515"
                        "paginaFinal" => "523"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14721768"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            11 => array:3 [
              "identificador" => "bib12"
              "etiqueta" => "12&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Efectos de la radiaci&#243;n ultravioleta sobre el sistema inmunitario&#46; Implicaciones terap&#233;uticas"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "J&#46;M&#46; Carrascosa"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Piel"
                        "fecha" => "2004"
                        "volumen" => "19"
                        "paginaInicial" => "303"
                        "paginaFinal" => "312"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            12 => array:3 [
              "identificador" => "bib13"
              "etiqueta" => "13&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Epidermodysplasia verruciformisassociated papillomavirus infection complicating human immunodeficiency virus disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "T&#46;G&#46; Berger"
                            1 => "W&#46;S&#46; Sawchuk"
                            2 => "C&#46; Leonardi"
                            3 => "A&#46; Langenberg"
                            4 => "J&#46; Tappero"
                            5 => "P&#46;E&#46; Leboit"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Br J Dermatol"
                        "fecha" => "1991"
                        "volumen" => "124"
                        "paginaInicial" => "79"
                        "paginaFinal" => "83"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1847068"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            13 => array:3 [
              "identificador" => "bib14"
              "etiqueta" => "14&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Epidermodysplasia verruciformis in a patient with Hodgkin&#39;s disease&#58; characterization of a new papilloma virus type and interferon treatment"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "G&#46; Gross"
                            1 => "K&#46; Ellinger"
                            2 => "A&#46; Roussaki"
                            3 => "P&#46;G&#46; Fuchs"
                            4 => "H&#46;H&#46; Peter"
                            5 => "H&#46; Pfister"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Invest Dermatol"
                        "fecha" => "1989"
                        "volumen" => "91"
                        "paginaInicial" => "43"
                        "paginaFinal" => "48"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2838553"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            14 => array:3 [
              "identificador" => "bib15"
              "etiqueta" => "15&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Epidermodysplasia verruciformis associated with severe immunodeficiency&#44; lymphoma&#44; and disseminated molluscum contagiosum"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "L&#46;D&#46; Slawsky"
                            1 => "R&#46;T&#46; Gilson"
                            2 => "A&#46;J&#46; Hockley"
                            3 => "L&#46;F&#46; Libow"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Am Acad Dermatol"
                        "fecha" => "1992"
                        "volumen" => "27"
                        "paginaInicial" => "448"
                        "paginaFinal" => "450"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1401282"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            15 => array:3 [
              "identificador" => "bib16"
              "etiqueta" => "16&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Swollen keratinocytes&#58; a histologic marker of unusual human papillomavirus-type infection and immunosuppression"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "N&#46;S&#46; Penneys"
                            1 => "A&#46; Friend"
                            2 => "W&#46;Y&#46; Zhu"
                            3 => "C&#46; Leonardi"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Cutan Pathol"
                        "fecha" => "1992"
                        "volumen" => "12"
                        "paginaInicial" => "217"
                        "paginaFinal" => "220"
                        "itemHostRev" => array:3 [
                          "pii" => "S001651071002331X"
                          "estado" => "S300"
                          "issn" => "00165107"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            16 => array:3 [
              "identificador" => "bib17"
              "etiqueta" => "17&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "M&#233;todos moleculares de detecci&#243;n de mutaciones en dermatolog&#237;a"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "P&#46; Unamuno"
                            1 => "R&#46; G&#243;nzalez Sarmiento"
                            2 => "S&#46; Mallo"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Piel"
                        "fecha" => "2004"
                        "volumen" => "19"
                        "paginaInicial" => "107"
                        "paginaFinal" => "114"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            17 => array:3 [
              "identificador" => "bib18"
              "etiqueta" => "18&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Bioestad&#237;stica&#46; M&#233;todos estad&#237;sticos para investigadores"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "J&#46;M&#46; Dom&#233;nech Massons"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Libro" => array:3 [
                        "fecha" => "1982"
                        "editorial" => "Herder"
                        "editorialLocalizacion" => "Barcelona"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            18 => array:3 [
              "identificador" => "bib19"
              "etiqueta" => "19&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "&#191;Qu&#233; es una odds ratio&#63;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "M&#46; Mart&#237;nez Gonz&#225;lez"
                            1 => "J&#46; Irala Est&#233;vez"
                            2 => "F&#46; Guill&#233;n Grima"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Med Clin &#40;Barc&#41;"
                        "fecha" => "1999"
                        "volumen" => "112"
                        "paginaInicial" => "416"
                        "paginaFinal" => "422"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            19 => array:3 [
              "identificador" => "bib20"
              "etiqueta" => "20&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Carcinomas espinocelulares"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "S&#46; Y&#225;&#241;ez-D&#237;az"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "LibroEditado" => array:4 [
                        "titulo" => "Tumores Cut&#225;neos"
                        "paginaInicial" => "97"
                        "paginaFinal" => "116"
                        "serieFecha" => "1999"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            20 => array:3 [
              "identificador" => "bib21"
              "etiqueta" => "21&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Carcinoma espinocelular cut&#225;neo y papilomavirus"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "R&#46; Corbal&#225;n-V&#233;lez"
                            1 => "J&#46;A&#46; Ruiz-Maci&#225;"
                            2 => "C&#46; Brufau"
                            3 => "F&#46;J&#46; Carapeto"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Actas Dermosifiliogr"
                        "fecha" => "2007"
                        "volumen" => "98"
                        "paginaInicial" => "583"
                        "paginaFinal" => "593"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17961447"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            21 => array:3 [
              "identificador" => "bib22"
              "etiqueta" => "22&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Detection of epidermodysplasia verruciformis-like human papillomavirus types in malignant and premalignant skin lesions of renal transplant recipients"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "L&#46;M&#46; Tieben"
                            1 => "R&#46;J&#46; Berkhout"
                            2 => "H&#46;L&#46; Smits"
                            3 => "J&#46;N&#46; Bouves Bavinck"
                            4 => "B&#46;J&#46; Vermeer"
                            5 => "J&#46;A&#46; Bruijn"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Br J Dermatol"
                        "fecha" => "1994"
                        "volumen" => "131"
                        "paginaInicial" => "226"
                        "paginaFinal" => "230"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7917987"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            22 => array:3 [
              "identificador" => "bib23"
              "etiqueta" => "23&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Detection of human papillomavirus type 5 DNA in skin cancers of an immunosupressed renal allograft recipient"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "M&#46;A&#46; Lutzner"
                            1 => "G&#46; Orth"
                            2 => "V&#46; Dutronquay"
                            3 => "M&#46;F&#46; Ducasse"
                            4 => "H&#46; Kreis"
                            5 => "J&#46; Crosnier"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Lancet"
                        "fecha" => "1983"
                        "volumen" => "2"
                        "paginaInicial" => "422"
                        "paginaFinal" => "424"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/6147500"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            23 => array:3 [
              "identificador" => "bib24"
              "etiqueta" => "24&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Human papillomavirus type 5 is commonly present in immunosuppressed and immunocompetent individuals"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "I&#46;L&#46; Boxman"
                            1 => "L&#46;H&#46; Mulder"
                            2 => "A&#46; Russell"
                            3 => "J&#46;N&#46; Bouwes Bavinck"
                            4 => "A&#46; Green"
                            5 => "J&#46; Ter Schegget"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Br J Dermatol"
                        "fecha" => "1999"
                        "volumen" => "141"
                        "paginaInicial" => "246"
                        "paginaFinal" => "249"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10468795"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            24 => array:3 [
              "identificador" => "bib25"
              "etiqueta" => "25&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Use of polymerase chain reaction amplification for the detection of genital human papillomavirus"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "M&#46;M&#46; Manos"
                            1 => "Y&#46; Ting"
                            2 => "D&#46;K&#46; Wright"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Cancer Cel"
                        "fecha" => "1989"
                        "volumen" => "7"
                        "paginaInicial" => "209"
                        "paginaFinal" => "214"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            25 => array:3 [
              "identificador" => "bib26"
              "etiqueta" => "26&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Detecci&#243;n y tipado de papilomavirus humano por amplificaci&#243;n gen&#243;mica en biopsias&#44; frotis y orina"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "A&#46; Mart&#237;nez"
                            1 => "R&#46; N&#225;s"
                            2 => "C&#46; LaCruz"
                            3 => "T&#46; Hell&#237;n"
                            4 => "J&#46;C&#46; Tercero"
                            5 => "E&#46; Valverde"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Acta Ginecol&#243;gica"
                        "fecha" => "1995"
                        "volumen" => "52"
                        "paginaInicial" => "51"
                        "paginaFinal" => "56"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            26 => array:3 [
              "identificador" => "bib27"
              "etiqueta" => "27&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Comparison of polymerase chain reaction and catalyzed signal amplification in situ hybridization methods for human papillomavirus detection in paraffin-embedded cervical preneoplastic and neoplastic lesions"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "M&#46;M&#46; Dabic"
                            1 => "L&#46; Hlupic"
                            2 => "D&#46; Babic"
                            3 => "S&#46; Jukic"
                            4 => "S&#46; Seiwerth"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.arcmed.2004.07.004"
                      "Revista" => array:6 [
                        "tituloSerie" => "Arch Med Res"
                        "fecha" => "2004"
                        "volumen" => "35"
                        "paginaInicial" => "511"
                        "paginaFinal" => "516"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15631876"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
          ]
        ]
      ]
    ]
  ]
  "idiomaDefecto" => "en"
  "url" => "/15782190/0000009900000004/v1_201304241431/S1578219008702506/v1_201304241431/en/main.assets"
  "Apartado" => array:4 [
    "identificador" => "6155"
    "tipo" => "SECCION"
    "en" => array:2 [
      "titulo" => "Original Articles"
      "idiomaDefecto" => true
    ]
    "idiomaDefecto" => "en"
  ]
  "PDF" => "https://static.elsevier.es/multimedia/15782190/0000009900000004/v1_201304241431/S1578219008702506/v1_201304241431/en/main.pdf?idApp=UINPBA000044&text.app=https://actasdermo.org/"
  "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1578219008702506?idApp=UINPBA000044"
]
Share
Journal Information
Vol. 99. Issue 4.
Pages 269-274 (May 2008)
Share
Share
Download PDF
More article options
Vol. 99. Issue 4.
Pages 269-274 (May 2008)
Original articles
Full text access
Epidermodysplasia Verruciformis-Like Cells as Histologic Markers of Immunosuppression: Review of 229 Squamous Cell Carcinomas*
Las Células Tipo Epidermodisplasia Verruciforme Como Marcador Histológico de Inmunodepresión: Revisión de 229 Carcinomas Espinocelulares
Visits
6033
R. Corbalán-Véleza,
Corresponding author
raulcorb@gmail.com

Correspondence: Servicio de Dermatología, Hospital Universitario Virgen de la Arrixaca, Ctra. Murcia-Cartagena, s/n, 30120 El Palmar, Murcia, Spain.
, J.A. Ruiz-Maciáb, C. Brufauc, J.M. López-Lozanod, E. Martínez-Barbae, J. Martínez-Escribanoa, F.J. Carapetof
a Servicio de Dermatología, Hospital Universitario Virgen de la Arrixaca, Murcia, Spain
b Servicio de Anatomía Patológica, Hospital Vega Baja, Orihuela, Alicante, Spain
c Servicio de Dermatología, Hospital General Reina Sofía, Murcia, Spain
d Servicio de Medicina Preventiva, Hospital Vega Baja, Orihuela, Alicante, Spain
e Servicio de Anatomía Patológica, Hospital Universitario Virgen de la Arrixaca, Murcia, Spain
f Servicio de Dermatología, Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain*
This item has received
Article information
Abstract
Introduction

Epidermodysplasia verruciformis (EV) is associated with greater susceptibility to infection by certain oncogenic subtypes of human papillomavirus (HPV). Among other histologic findings, large, clear, oval or rounded cells (EV cells) are observed in the granular layer in EV, and some authors consider these cells to be markers of immunosuppression.

Material and Methods

We analyzed 229 squamous cell carcinomas (SCC) to determine whether EV cells were present and to assess whether their presence was associated either with localized or cutaneous immunosuppression (tumors with signs of severe chronic actinic damage or severe stasis dermatitis) or with systemic immunosuppression (immunocompromised or elderly patients).

Results

We observed EV cells in 33 SCC. No statistically significant relationship was observed between the presence of EV cells and immunosuppression. We performed polymerase chain reaction in 8 lesions, but the results were not informative as the DNA was denatured.

Conclusions

We found no relationship between the presence of EV cells and localized or systemic immunosuppression, possibly because the sample was inadequate (almost all SCC studied were associated with signs of immunosuppression, irrespective of the presence or absence of EV cells). Further studies will be required to compare lesions associated with immunosuppression with those in which immunosuppression is absent. The presence of EV cells may be the result of cytopathic effects of certain HPV subtypes, such as HPV 5 or 8, but this will need to be demonstrated using techniques such as polymerase chain reaction.

Key words:
epidermodysplasia verruciformis
immunosuppression
papillomavirus
solar elastosis
Resumen
Introducción

La epidermodisplasia verruciforme (EV) es una enfermedad en la que existe una mayor susceptibilidad genética a la infección por determinados subtipos oncogénicos del virus del papiloma humano (VPH). Entre otros hallazgos histológicos, en la EV suelen observarse unas células claras, grandes, ovaladas o redondeadas (células EV) en la capa granulosa, que según algunos autores se podrían considerar como un marcador histológico de inmunodepresión.

Material y métodos

Hemos estudiado 229 carcinomas espinocelulares (CE) para valorar si presentaban células EV y si se relacionaban con inmunodepresión, tanto localizada o cutánea (tumores con signos de intenso daño solar crónico o con una dermatitis de estasis intensa), como sistémica (pacientes inmunodeprimidos o ancianos).

Resultados

Observamos células EV en 33 carcinomas. No hemos encontrado relación significativa entre la existencia de células EV e inmunodepresión. Realizamos reacción en cadena de la polimerasa (PCR) en 8 lesiones, pero los resultados no fueron valorables porque el ADN estaba desnaturalizado.

Conclusiones

No hemos demostrado relación entre las células EV e inmunodepresión, localizada o sistémica, posiblemente porque la muestra no era adecuada (se podría considerar que prácticamente todos los CE estudiados se asociaban a signos de inmunodepresión, tanto aquellos que presentaban células EV como los que no). Serían necesarios más estudios que comparasen lesiones asociadas a inmunodepresión con otras que no. Es posible que estas células EV sean el resultado de los efectos citopáticos de determinados subtipos de VPH, como el VPH-5 o el VPH-8, aunque sería necesario demostrar esta hipótesis mediante técnicas de PCR o similar.

Palabras clave:
epidermodisplasia verruciforme
inmunodepresión
papilomavirus
elastosis solar
Full text is only aviable in PDF
References
[1.]
S. Majewski, S. Jablonska.
Epidermodysplasia verruciformis as a model of Human Papillomavirus-inducel genetic cancer of the skin.
Arch Dermatol, 131 (1995), pp. 1312-1318
[2.]
V.P. Sánchez-García, A. Sanz, C. Eloy, A. Vera, T. Martín, F. Sánchez-Fajardo.
Epidermodisplasia verruciforme.
Actas Dermosifiliogr, 96 (2005), pp. 531-533
[3.]
W.R. de Oliveira, C. Festa Neto, P.L. Rady, S.K. Tyring.
Clinical aspects of epidermodysplasia verruciformis.
J Eur Acad Dermatol Venereol, 17 (2003), pp. 394-398
[4.]
S. Majewski, E. Skipinska-Rozewska, S. Jablonska, M. Wasik, J. Misiewicz, G. Orth.
Partial defects of cell-mediated immunity in patients with epidermodysplasia verruciformis.
J Am Acad Dermatol, 15 (1986), pp. 966-973
[5.]
S. Majewski, J. Malejczyk, S. Jablonska, J. Misiewicz, L. Rudnicka, S. Obalek, et al.
Natural cell-mediated cytotoxicity against various target cells in patients with epidermodysplasia verruciformis.
J Am Acad Dermatol, 22 (1990), pp. 423-427
[6.]
G.J. Nuovo, M. Ishag.
The histologic spectrum of Epidermodysplasia Verruciformis.
Am J Surg Pathol, 24 (2000), pp. 1400-1406
[7.]
D. Weedon.
Viral diseases.
Skin Pathology, pp. 583-603
[8.]
D. Berg, C.C. Otley.
Skin cancer in organ transplant recipients: Epidemiology, pathogenesis, and management.
J Am Acad Dermatol, 47 (2002), pp. 1-17
[9.]
F.F. Fagnoni, R. Vescovini, G. Passeri, G. Bologna, M. Pedrazzoni, G. Lavagetto, et al.
Shortage of circulating naive CD8 ??T cells provides new insights on immunodeficiency in aging.
Blood, 95 (2000), pp. 2860-2868
[10.]
V.G. Villarrubia, L.A. Costa, M. Pérez, S. Vidal, P. Jaen.
Epidemiología e inmunopatogenia del cáncer cutáneo no melanoma. El papel iniciador y promotor del VPH.
Piel, 16 (2001), pp. 428-438
[11.]
F. Aubin.
Mechanism involved in ultraviolet light-induced immunosuppression.
Eur J Dermatol, 13 (2003), pp. 515-523
[12.]
J.M. Carrascosa.
Efectos de la radiación ultravioleta sobre el sistema inmunitario. Implicaciones terapéuticas.
Piel, 19 (2004), pp. 303-312
[13.]
T.G. Berger, W.S. Sawchuk, C. Leonardi, A. Langenberg, J. Tappero, P.E. Leboit.
Epidermodysplasia verruciformisassociated papillomavirus infection complicating human immunodeficiency virus disease.
Br J Dermatol, 124 (1991), pp. 79-83
[14.]
G. Gross, K. Ellinger, A. Roussaki, P.G. Fuchs, H.H. Peter, H. Pfister.
Epidermodysplasia verruciformis in a patient with Hodgkin's disease: characterization of a new papilloma virus type and interferon treatment.
J Invest Dermatol, 91 (1989), pp. 43-48
[15.]
L.D. Slawsky, R.T. Gilson, A.J. Hockley, L.F. Libow.
Epidermodysplasia verruciformis associated with severe immunodeficiency, lymphoma, and disseminated molluscum contagiosum.
J Am Acad Dermatol, 27 (1992), pp. 448-450
[16.]
N.S. Penneys, A. Friend, W.Y. Zhu, C. Leonardi.
Swollen keratinocytes: a histologic marker of unusual human papillomavirus-type infection and immunosuppression.
J Cutan Pathol, 12 (1992), pp. 217-220
[17.]
P. Unamuno, R. Gónzalez Sarmiento, S. Mallo.
Métodos moleculares de detección de mutaciones en dermatología.
Piel, 19 (2004), pp. 107-114
[18.]
J.M. Doménech Massons.
Bioestadística. Métodos estadísticos para investigadores.
Herder, (1982),
[19.]
M. Martínez González, J. Irala Estévez, F. Guillén Grima.
¿Qué es una odds ratio?.
Med Clin (Barc), 112 (1999), pp. 416-422
[20.]
S. Yáñez-Díaz.
Carcinomas espinocelulares.
Tumores Cutáneos, pp. 97-116
[21.]
R. Corbalán-Vélez, J.A. Ruiz-Maciá, C. Brufau, F.J. Carapeto.
Carcinoma espinocelular cutáneo y papilomavirus.
Actas Dermosifiliogr, 98 (2007), pp. 583-593
[22.]
L.M. Tieben, R.J. Berkhout, H.L. Smits, J.N. Bouves Bavinck, B.J. Vermeer, J.A. Bruijn, et al.
Detection of epidermodysplasia verruciformis-like human papillomavirus types in malignant and premalignant skin lesions of renal transplant recipients.
Br J Dermatol, 131 (1994), pp. 226-230
[23.]
M.A. Lutzner, G. Orth, V. Dutronquay, M.F. Ducasse, H. Kreis, J. Crosnier.
Detection of human papillomavirus type 5 DNA in skin cancers of an immunosupressed renal allograft recipient.
Lancet, 2 (1983), pp. 422-424
[24.]
I.L. Boxman, L.H. Mulder, A. Russell, J.N. Bouwes Bavinck, A. Green, J. Ter Schegget.
Human papillomavirus type 5 is commonly present in immunosuppressed and immunocompetent individuals.
Br J Dermatol, 141 (1999), pp. 246-249
[25.]
M.M. Manos, Y. Ting, D.K. Wright.
Use of polymerase chain reaction amplification for the detection of genital human papillomavirus.
Cancer Cel, 7 (1989), pp. 209-214
[26.]
A. Martínez, R. Nás, C. LaCruz, T. Hellín, J.C. Tercero, E. Valverde, et al.
Detección y tipado de papilomavirus humano por amplificación genómica en biopsias, frotis y orina.
Acta Ginecológica, 52 (1995), pp. 51-56
[27.]
M.M. Dabic, L. Hlupic, D. Babic, S. Jukic, S. Seiwerth.
Comparison of polymerase chain reaction and catalyzed signal amplification in situ hybridization methods for human papillomavirus detection in paraffin-embedded cervical preneoplastic and neoplastic lesions.
Arch Med Res, 35 (2004), pp. 511-516

2006 August C. Stiefel Award.

Copyright © 2008. Academia Española de Dermatología y Venereología and Elsevier España, S.L.
Download PDF
Idiomas
Actas Dermo-Sifiliográficas
Article options
Tools
es en

¿Es usted profesional sanitario apto para prescribir o dispensar medicamentos?

Are you a health professional able to prescribe or dispense drugs?