{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T19:08:41Z","timestamp":1790968121697,"version":"4.1.0"},"reference-count":37,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2023,1,15]],"date-time":"2023-01-15T00:00:00Z","timestamp":1673740800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"published-print":{"date-parts":[[2023,4]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Each category of vulvar squamous cell carcinoma (VSCC), human papillomavirus (HPV)\u2010associated and HPV\u2010independent, arises on a specific intra\u2010epithelial precursor: high\u2010grade squamous intra\u2010epithelial lesions (HSIL) and differentiated vulvar intra\u2010epithelial neoplasia (dVIN), respectively. However, a subset of HPV\u2010independent VSCC arises on an intra\u2010epithelial precursor closely mimicking HSIL. We aimed to explore the clinicopathological features of the HPV\u2010independent tumours with HSIL\u2010like lesions and compare them with HPV\u2010independent VSCC with dVIN and HPV\u2010associated tumours with HSIL.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>We retrospectively identified 105 cases of surgically treated VSCC with adjacent intra\u2010epithelial precursors. The cases were classified into three groups based on the HPV status and the adjacent precursor identified: (i) HPV\u2010associated VSCC with HSIL (<jats:italic>n<\/jats:italic>\u00a0=\u00a026), (ii) HPV\u2010independent VSCC with dVIN lesions (<jats:italic>n<\/jats:italic>\u00a0=\u00a054) and (iii) HPV\u2010independent VSCC with HSIL\u2010like lesions (<jats:italic>n<\/jats:italic>\u00a0=\u00a025). We analysed the histological and clinical features including the recurrence\u2010free survival and disease\u2010specific survival in the three groups. Patients with HPV\u2010independent VSCC with HSIL\u2010like lesions and with dVIN were older than patients with HPV\u2010associated VSCC (76 and 77\u2009versus 66\u2009years, respectively, <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001). HPV\u2010independent VSCC with HSIL\u2010like lesions recurred more frequently [hazard ratio (HR)\u00a0=\u00a03.87; <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001] than HPV\u2010independent VSCC with dVIN (HR\u00a0=\u00a02.27; <jats:italic>P<\/jats:italic>\u00a0=\u00a00.1) and HPV\u2010associated VSCC (HR\u00a0=\u00a01). In the multivariate analysis, HPV\u2010independent VSCC with HSIL\u2010like lesions remained significant for recurrence. No differences in disease\u2010specific survival were observed between the three groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Even though VSCC with HSIL\u2010like lesions are not associated with higher mortality, they are more likely to recur and might benefit from more intensive treatment strategies and closer surveillance after treatment.<\/jats:p><\/jats:sec>","DOI":"10.1111\/his.14860","type":"journal-article","created":{"date-parts":[[2023,1,3]],"date-time":"2023-01-03T04:18:07Z","timestamp":1672719487000},"page":"731-744","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Vulvar squamous cell carcinoma arising on human\u00a0papillomavirus\u2010independent precursors mimicking high\u2010grade squamous intra\u2010epithelial lesion: a distinct and highly recurrent subtype of vulvar cancer"],"prefix":"10.1111","volume":"82","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4809-8102","authenticated-orcid":false,"given":"N\u00faria","family":"Carreras\u2010Dieguez","sequence":"first","affiliation":[{"name":"Clinical Institute of Gynecology, Obstetrics, and Neonatology Hospital Cl\u00ednic de Barcelona, Universitat de Barcelona  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9935-9045","authenticated-orcid":false,"given":"Adela","family":"Saco","sequence":"additional","affiliation":[{"name":"Department of Pathology Hospital Cl\u00ednic of Barcelona, University of Barcelona  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2178-2403","authenticated-orcid":false,"given":"Marta","family":"del Pino","sequence":"additional","affiliation":[{"name":"Clinical Institute of Gynecology, Obstetrics, and Neonatology Hospital Cl\u00ednic de Barcelona, Universitat de Barcelona  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cl\u00e0udia","family":"Pumarola","sequence":"additional","affiliation":[{"name":"Clinical Institute of Gynecology, Obstetrics, and Neonatology Hospital Cl\u00ednic de Barcelona, Universitat de Barcelona  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo L\u00f3pez","family":"del Campo","sequence":"additional","affiliation":[{"name":"Department of Pathology Hospital Cl\u00ednic of Barcelona, University of Barcelona  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0025-2318","authenticated-orcid":false,"given":"Carolina","family":"Manzotti","sequence":"additional","affiliation":[{"name":"Department of Pathology Hospital Cl\u00ednic of Barcelona, University of Barcelona  Barcelona Spain"},{"name":"Barcelona Institute for Global Health (ISGlobal) Hospital Cl\u00ednic\u2010Universitat de Barcelona  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana","family":"Garcia","sequence":"additional","affiliation":[{"name":"Department of Pathology Hospital Cl\u00ednic of Barcelona, University of Barcelona  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2943-3550","authenticated-orcid":false,"given":"Lorena","family":"Marimon","sequence":"additional","affiliation":[{"name":"Department of Pathology Hospital Cl\u00ednic of Barcelona, University of Barcelona  Barcelona Spain"},{"name":"Barcelona Institute for Global Health (ISGlobal) Hospital Cl\u00ednic\u2010Universitat de Barcelona  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8164-8639","authenticated-orcid":false,"given":"Sherley","family":"Diaz\u2010Mercedes","sequence":"additional","affiliation":[{"name":"Department of Pathology Hospital Cl\u00ednic of Barcelona, University of Barcelona  Barcelona Spain"},{"name":"Barcelona Institute for Global Health (ISGlobal) Hospital Cl\u00ednic\u2010Universitat de Barcelona  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8129-9897","authenticated-orcid":false,"given":"Pere","family":"Fuste","sequence":"additional","affiliation":[{"name":"Clinical Institute of Gynecology, Obstetrics, and Neonatology Hospital Cl\u00ednic de Barcelona, Universitat de Barcelona  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6675-3425","authenticated-orcid":false,"given":"Maria Teresa","family":"Rodrigo\u2010Calvo","sequence":"additional","affiliation":[{"name":"Department of Pathology Hospital Cl\u00ednic of Barcelona, University of Barcelona  Barcelona 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