{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T19:05:40Z","timestamp":1790967940933,"version":"4.1.0"},"reference-count":113,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2012,11,27]],"date-time":"2012-11-27T00:00:00Z","timestamp":1353974400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"published-print":{"date-parts":[[2013,1]]},"abstract":"<jats:p>\n                    Vulvar squamous cell carcinoma (\n                    <jats:styled-content style=\"fixed-case\">VSCC<\/jats:styled-content>\n                    ) accounts for &gt;90% of the malignant tumours of the vulva. Most\n                    <jats:styled-content style=\"fixed-case\">VSCC<\/jats:styled-content>\n                    s originate in intraepithelial lesions, named vulvar intraepithelial neoplasia (\n                    <jats:styled-content style=\"fixed-case\">VIN<\/jats:styled-content>\n                    ), that precede the development of\n                    <jats:styled-content style=\"fixed-case\">VSCC<\/jats:styled-content>\n                    by a variable period of time. Strong evidence has accumulated showing that there are two different aetiopathogenic pathways for the development of\n                    <jats:styled-content style=\"fixed-case\">VSCC<\/jats:styled-content>\n                    and\n                    <jats:styled-content style=\"fixed-case\">VIN<\/jats:styled-content>\n                    , one associated with infection by human papillomavirus (\n                    <jats:styled-content style=\"fixed-case\">HPV<\/jats:styled-content>\n                    ), and a second independent of\n                    <jats:styled-content style=\"fixed-case\">HPV<\/jats:styled-content>\n                    infection. These two different types of\n                    <jats:styled-content style=\"fixed-case\">VSCC<\/jats:styled-content>\n                    have different epidemiological, pathological and clinical characteristics, and should therefore be considered as two separate entities. Histologically,\n                    <jats:styled-content style=\"fixed-case\">HPV<\/jats:styled-content>\n                    \u2010associated\n                    <jats:styled-content style=\"fixed-case\">VSCC<\/jats:styled-content>\n                    s are of the basaloid or warty type, and arise from\n                    <jats:styled-content style=\"fixed-case\">VIN<\/jats:styled-content>\n                    of the usual type. Inactivation of p53 and the retinoblastoma tumour suppressor gene product by the viral gene products\n                    <jats:styled-content style=\"fixed-case\">E<\/jats:styled-content>\n                    6 and\n                    <jats:styled-content style=\"fixed-case\">E<\/jats:styled-content>\n                    7 is involved in the process of malignant transformation.\n                    <jats:styled-content style=\"fixed-case\">HPV<\/jats:styled-content>\n                    \u2010independent\n                    <jats:styled-content style=\"fixed-case\">VSCC<\/jats:styled-content>\n                    s are histologically keratinizing, are associated with differentiated\n                    <jats:styled-content style=\"fixed-case\">VIN<\/jats:styled-content>\n                    and lichen sclerosus, and frequently show mutations of p53. p16\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:sup>INK4a<\/jats:sup>\n                    <\/jats:styled-content>\n                    and p53 immunostaining can be useful for classifying\n                    <jats:styled-content style=\"fixed-case\">VSCC<\/jats:styled-content>\n                    into\n                    <jats:styled-content style=\"fixed-case\">HPV<\/jats:styled-content>\n                    \u2010associated or\n                    <jats:styled-content style=\"fixed-case\">HPV<\/jats:styled-content>\n                    \u2010independent. Although large, multicentre studies are needed to definitively assess the involvement of\n                    <jats:styled-content style=\"fixed-case\">HPV<\/jats:styled-content>\n                    in the prognosis of\n                    <jats:styled-content style=\"fixed-case\">VSCC<\/jats:styled-content>\n                    , most studies have not found clear differences in survival between\n                    <jats:styled-content style=\"fixed-case\">HPV<\/jats:styled-content>\n                    \u2010associated and\n                    <jats:styled-content style=\"fixed-case\">HPV<\/jats:styled-content>\n                    \u2010independent tumours.\n                  <\/jats:p>","DOI":"10.1111\/his.12034","type":"journal-article","created":{"date-parts":[[2012,9,18]],"date-time":"2012-09-18T10:52:13Z","timestamp":1347965533000},"page":"161-175","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":225,"title":["Pathways of vulvar intraepithelial neoplasia and squamous cell carcinoma"],"prefix":"10.1111","volume":"62","author":[{"given":"Marta","family":"del Pino","sequence":"first","affiliation":[{"name":"Faculty of Medicine Institute Clinic of Gynaecology, Obstetrics and Neonatology Hospital Clinic\u2010Institut d'Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS) University of Barcelona Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonardo","family":"Rodriguez\u2010Carunchio","sequence":"additional","affiliation":[{"name":"Department of Pathology Faculty of Medicine CRESIB (Centre de Recerca en Salut Internacional de Barcelona) Hospital Clinic University of Barcelona Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaume","family":"Ordi","sequence":"additional","affiliation":[{"name":"Department of Pathology Faculty of Medicine CRESIB (Centre de Recerca en Salut Internacional de Barcelona) Hospital Clinic University of Barcelona Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,11,27]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.AOG.0000210268.57527.a1"},{"key":"e_1_2_11_3_1","first-page":"179","volume-title":"Atlas of Tumor Pathology","author":"Norris HJ","year":"1992"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/00004347-199104000-00001"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000478-199302000-00005"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2559.2003.01578.x"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2559.2008.03098.x"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.pas.0000213251.82940.bf"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/00004347-200101000-00003"},{"key":"e_1_2_11_10_1","first-page":"973","article-title":"Report of the ISSVD Terminology Committee","volume":"31","author":"Wilkinson EJ","year":"1986","journal-title":"J. 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