{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T11:07:42Z","timestamp":1789556862536,"version":"build-2803163510"},"reference-count":37,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,10,15]],"date-time":"2023-10-15T00:00:00Z","timestamp":1697328000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100013034","name":"Direktoratet for internasjonalisering og kvalitetsutvikling i h\u00f8gare utdanning","doi-asserted-by":"publisher","award":["CPEA\u2010LT\u20102016\/10106"],"award-info":[{"award-number":["CPEA\u2010LT\u20102016\/10106"]}],"id":[{"id":"10.13039\/501100013034","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004257","name":"Helse Vest","doi-asserted-by":"publisher","award":["912260"],"award-info":[{"award-number":["912260"]}],"id":[{"id":"10.13039\/501100004257","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["obgyn.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acta Obstet Gynecol Scand"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Vulva squamous cell carcinoma (VSCC) develops through two separate molecular pathways\u2014one involving high\u2010risk human papilloma virus infection (HPV\u2010associated), and the other without HPV infection (HPV\u2010independent) often involving <jats:italic>TP53<\/jats:italic> mutation. HPV\u2010associated VSCC generally has a better progression\u2010free survival than HPV\u2010independent VSCC. The aim of this study was to determine <jats:italic>TP53<\/jats:italic> mutation status using immunohistochemistry, compare different methods of HPV detection and correlate both with survival in a retrospective cohort of 123 patients with VSCC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Material and methods<\/jats:title><jats:p>Immunohistochemistry for p53, Ki67 and p16<jats:sup>INK4A<\/jats:sup> (a surrogate marker for HPV infection) was performed on formalin\u2010fixed paraffin\u2010embedded tissues from a cohort of surgically treated VSCC patients to identify molecular subtypes of VSCC. Presence of HPV infection was detected by HPV DNA PCR and HPV mRNA in\u00a0situ hybridization (ISH). The Pearson chi\u2010square test and multivariable Cox regression model were used to investigate the association of different parameters with progression\u2010free survival and disease\u2010specific survival (DSS), and Kaplan\u2013Meier curves were used to show the association of different parameters with survival.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The results of p53 and p16<jats:sup>INK4A<\/jats:sup> immunohistochemistry confirmed three VSCC subtypes associated with different prognosis. The <jats:italic>TP53<\/jats:italic> mutation status was identified as an independent prognostic factor of worse progression\u2010free survival (<jats:italic>p<\/jats:italic>\u2009=\u20090.024) after adjustment for FIGO stage. p16<jats:sup>INK4A<\/jats:sup> immunohistochemistry, mRNA ISH, and DNA PCR had excellent concordance in terms of HPV detection. According to the multivariable Cox regression model, the presence of hrHPV mRNA correlated significantly with increased progression\u2010free survival (<jats:italic>p<\/jats:italic>\u2009=\u20090.040) and DSS (<jats:italic>p<\/jats:italic>\u2009=\u20090.045), after adjustment for other confounders.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>p53 and p16<jats:sup>INK4A<\/jats:sup> immunohistochemistry stratify VSCC cohort into three subtypes with <jats:italic>TP53<\/jats:italic>mutated patients having the worst prognosis. The detection of hrHPV mRNA by ISH was an independent predictor of increased survival. Thus, the combined detection of p53 and HPV mRNA might improve risk stratification in VSCC.<\/jats:p><\/jats:sec>","DOI":"10.1111\/aogs.14689","type":"journal-article","created":{"date-parts":[[2023,10,16]],"date-time":"2023-10-16T03:10:29Z","timestamp":1697425829000},"page":"165-175","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["<scp><i>TP53<\/i><\/scp> mutation and human papilloma virus status as independent prognostic factors in a Norwegian cohort of vulva squamous cell carcinoma"],"prefix":"10.1111","volume":"103","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4378-2869","authenticated-orcid":false,"given":"Harsh Nitin","family":"Dongre","sequence":"first","affiliation":[{"name":"Center for Cancer Biomarkers CCBIO and Gade Laboratory of Pathology, Department of Clinical Medicine University of Bergen  Bergen Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rammah","family":"Elnour","sequence":"additional","affiliation":[{"name":"Center for Cancer Biomarkers CCBIO and Gade Laboratory of Pathology, Department of Clinical Medicine University of Bergen  Bergen Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stian","family":"Tornaas","sequence":"additional","affiliation":[{"name":"Center for Cancer Biomarkers CCBIO and Gade Laboratory of Pathology, Department of Clinical Medicine University of Bergen  Bergen Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siren","family":"Fromreide","sequence":"additional","affiliation":[{"name":"Center for Cancer Biomarkers CCBIO and Gade Laboratory of Pathology, Department of Clinical Medicine University of Bergen  Bergen Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liv Cecilie Vestrheim","family":"Thomsen","sequence":"additional","affiliation":[{"name":"Center for Cancer Biomarkers CCBIO, Department of Clinical Science University of Bergen  Bergen Norway"},{"name":"Department of Obstetrics and Gynecology Haukeland University Hospital  Bergen Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingrid Benedicte Moss","family":"Kolseth","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Haukeland University Hospital  Bergen Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth Sivy","family":"Nginamau","sequence":"additional","affiliation":[{"name":"Department of Pathology, Laboratory Clinic Haukeland University Hospital  Bergen Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne Christine","family":"Johannessen","sequence":"additional","affiliation":[{"name":"Center for Cancer Biomarkers CCBIO and Gade Laboratory of Pathology, Department of Clinical Medicine University of Bergen  Bergen Norway"},{"name":"Department of Pathology, Laboratory Clinic Haukeland University Hospital  Bergen Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olav Karsten","family":"Vintermyr","sequence":"additional","affiliation":[{"name":"Center for Cancer Biomarkers CCBIO and Gade Laboratory of Pathology, Department of Clinical Medicine University of Bergen  Bergen Norway"},{"name":"Department of Pathology, Laboratory Clinic Haukeland University Hospital  Bergen Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela Elena","family":"Costea","sequence":"additional","affiliation":[{"name":"Center for Cancer Biomarkers CCBIO and Gade Laboratory of Pathology, Department of Clinical Medicine University of Bergen  Bergen Norway"},{"name":"Department of Pathology, Laboratory Clinic Haukeland University Hospital  Bergen Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0240-2770","authenticated-orcid":false,"given":"Line","family":"Bj\u00f8rge","sequence":"additional","affiliation":[{"name":"Center for Cancer Biomarkers CCBIO, Department of Clinical Science University of Bergen  Bergen Norway"},{"name":"Department of Obstetrics and Gynecology Haukeland University Hospital  Bergen 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