{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T05:11:11Z","timestamp":1792300271428,"version":"4.4.0"},"reference-count":25,"publisher":"SAGE Publications","issue":"6","license":[{"start":{"date-parts":[[2017,5,26]],"date-time":"2017-05-26T00:00:00Z","timestamp":1495756800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Tumori"],"published-print":{"date-parts":[[2017,11]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Two different types of vulvar intraepithelial neoplasia (VIN), HPV-related and HPV-unrelated, should be considered as two separate entities with different management options. The incidence of HPV-related VIN is increasing worldwide and is implicated in carcinogenesis. Our objective is to investigate the use of p16\n                      <jats:sup>INK4a<\/jats:sup>\n                      immunostaining or p16\n                      <jats:sup>INK4a<\/jats:sup>\n                      \/p53 double staining for the detection of HPV-related disease to overcome the problem that histological criteria often have significant overlap.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A systematic literature search was carried out in the online databases PubMed, EMBASE, Cochrane Library, Clincaltrials.gov and Scopus. The key search terms were HPV, VIN, p16\n                      <jats:sup>INK4a<\/jats:sup>\n                      immunochemistry and p53.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We found that nuclear and cytoplasmic immunostaining for p16\n                      <jats:sup>INK4a<\/jats:sup>\n                      was intense and diffuse in HPV-associated lesions and weak and focal in normal vulvar epithelium, nondysplastic lesions, lichen sclerosus and keratinizing vulvar squamous cell carcinoma. p53 nuclear immunostaining was always negative in HPV-related disease.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Our findings indicated that p16\n                      <jats:sup>INK4a<\/jats:sup>\n                      or p16\n                      <jats:sup>INK4a<\/jats:sup>\n                      \/p53 immunoreactivity, along with histological diagnosis, could be a convenient means to adequately classify VIN and its connection to HPV infection. Therefore, the clear recognition of HPV-associated VIN would lead to an appropriate strategy of treatment and follow-up.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.5301\/tj.5000642","type":"journal-article","created":{"date-parts":[[2017,6,2]],"date-time":"2017-06-02T05:57:16Z","timestamp":1496383036000},"page":"511-515","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":9,"title":["HPV-related Vulvar Diseases and Perspectives of p16\n                    <sup>INK4a<\/sup>\n                    Immunochemistry: A Review of the Literature"],"prefix":"10.1177","volume":"103","author":[{"given":"Angela","family":"Carrone","sequence":"first","affiliation":[{"name":"Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua - Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Riganelli","sequence":"additional","affiliation":[{"name":"Department of Gynecological, Obstetrical and Urological Sciences, \u201cSapienza\u201d University and Umberto I Polyclinic of Rome, Rome - Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Delia","family":"Savone","sequence":"additional","affiliation":[{"name":"Department of Gynecological, Obstetrical and Urological Sciences, \u201cSapienza\u201d University and Umberto I Polyclinic of Rome, Rome - Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Assunta","family":"Casorelli","sequence":"additional","affiliation":[{"name":"Department of Gynecological, Obstetrical and Urological Sciences, \u201cSapienza\u201d University and Umberto I Polyclinic of Rome, Rome - Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Merlino","sequence":"additional","affiliation":[{"name":"Department of Gynecological, Obstetrical and Urological Sciences, \u201cSapienza\u201d University and Umberto I Polyclinic of Rome, Rome - Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Pecorini","sequence":"additional","affiliation":[{"name":"Department of Gynecological, Obstetrical and Urological Sciences, \u201cSapienza\u201d University and Umberto I Polyclinic of Rome, Rome - Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Pecorella","sequence":"additional","affiliation":[{"name":"Department of Gynecological, Obstetrical and Urological Sciences, \u201cSapienza\u201d University and Umberto I Polyclinic of Rome, Rome - Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pasquale","family":"Mancino","sequence":"additional","affiliation":[{"name":"Department of Gynecological, Obstetrical and Urological Sciences, \u201cSapienza\u201d University and Umberto I Polyclinic of Rome, Rome - Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Grazia","family":"Piccioni","sequence":"additional","affiliation":[{"name":"Department of Gynecological, Obstetrical and Urological Sciences, \u201cSapienza\u201d University and Umberto I Polyclinic of Rome, Rome - Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierluigi","family":"Benedetti Panici","sequence":"additional","affiliation":[{"name":"Department of Gynecological, Obstetrical and Urological Sciences, \u201cSapienza\u201d University and Umberto I Polyclinic of Rome, Rome - Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2017,5,26]]},"reference":[{"key":"bibr1-tj.5000642","unstructured":"IARC. Cancer incidence in five continents, Vol. IX, 2007 http:\/\/www.iarc.fr\/en\/publications\/pdfs-online\/epi\/sp160\/CI5vol9.pdf. Accessed April 10, 2017."},{"key":"bibr2-tj.5000642","unstructured":"Cancer Research UK. Vulvar cancer incidence statistic http:\/\/www.cancerresearchuk.org\/about-cancer\/type\/vulval-cancer\/about\/risks-and-causes-of-vulval-cancer. Accessed April 10, 2017."},{"key":"bibr3-tj.5000642","unstructured":"Stat Fact Sheets SEER. Vulvar cancer http:\/\/seer.cancer.gov\/statfacts\/html\/vulva.html. 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Eur J Cancer."},{"key":"bibr15-tj.5000642","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2004.09.004"},{"key":"bibr16-tj.5000642","doi-asserted-by":"publisher","DOI":"10.1097\/00128360-200504000-00007"},{"key":"bibr17-tj.5000642","doi-asserted-by":"publisher","DOI":"10.1097\/LGT.0000000000000182"},{"issue":"3","key":"bibr18-tj.5000642","first-page":"289","volume":"17","author":"Reuschenbach M","year":"2013","journal-title":"Characterization of squamous cell cancers of the vulvar anterior fourchette by human papillomavirus, p16INK4a, and p53. J Low Genit Tract Dis."},{"issue":"1","key":"bibr19-tj.5000642","author":"Lawrie TA","year":"2016","journal-title":"Cochrane Database Syst Rev."},{"issue":"7","key":"bibr20-tj.5000642","first-page":"936","volume":"17","author":"Frega A","year":"2013","journal-title":"Eur Rev Med Pharmacol Sci."},{"key":"bibr21-tj.5000642","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-0528.1996.tb09772.x"},{"key":"bibr22-tj.5000642","doi-asserted-by":"publisher","DOI":"10.1097\/LGT.0000000000000204"},{"issue":"3","key":"bibr23-tj.5000642","first-page":"373","volume":"137","author":"Benedetti Panici P","year":"2015","journal-title":"A prospective study and literature review. 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