{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T13:45:50Z","timestamp":1791899150095,"version":"4.3.4"},"reference-count":37,"publisher":"Springer Science and Business Media LLC","license":[{"start":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T00:00:00Z","timestamp":1778457600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T00:00:00Z","timestamp":1778457600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Virchows Arch"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Vulvar squamous cell carcinoma (VSCC) comprises biologically distinct subtypes with divergent molecular profiles and clinical behaviors. In this study, we performed comprehensive genomic profiling of 48 primary VSCCs, integrating mutational and copy number data with HPV status and clinicopathological parameters. Tumors were stratified into HPV-associated (HPVA), HPV-independent (HPVI), and a third proposed subgroup characterized by HPV negativity and wild-type TP53 status. Overall, 650 somatic mutations were identified, with\n                    <jats:italic>TP53<\/jats:italic>\n                    ,\n                    <jats:italic>TERT<\/jats:italic>\n                    promoter,\n                    <jats:italic>NOTCH1<\/jats:italic>\n                    ,\n                    <jats:italic>PIK3CA<\/jats:italic>\n                    , and\n                    <jats:italic>CDKN2A<\/jats:italic>\n                    being the most frequently altered genes. HPVA VSCCs exhibited a higher mutational burden and enrichment of\n                    <jats:italic>PIK3CA<\/jats:italic>\n                    ,\n                    <jats:italic>NOTCH1<\/jats:italic>\n                    , and\n                    <jats:italic>MLL2<\/jats:italic>\n                    mutations, consistent with APOBEC-driven mutagenesis. HPVI VSCCs showed frequent\n                    <jats:italic>TP53<\/jats:italic>\n                    ,\n                    <jats:italic>TERTp<\/jats:italic>\n                    , and\n                    <jats:italic>CDKN2A<\/jats:italic>\n                    mutations, along with an age-related mutational signature. Copy number alterations were more common in HPVI tumors, with recurrent amplifications in\n                    <jats:italic>CCND1<\/jats:italic>\n                    ,\n                    <jats:italic>FGF3\/4\/19<\/jats:italic>\n                    , and CDK pathway genes. Six VSCCs lacked both HPV association and\n                    <jats:italic>TP53<\/jats:italic>\n                    mutations, supporting the existence of a third molecular subtype, with frequent\n                    <jats:italic>TERTp<\/jats:italic>\n                    mutations and limited additional alterations. No significant survival differences were observed between subtypes, although nodal status remained prognostically relevant. These findings refine the molecular taxonomy of VSCC, support the recognition of a third genomic subgroup, and highlight subtype-specific therapeutic targets.\n                  <\/jats:p>","DOI":"10.1007\/s00428-026-04422-4","type":"journal-article","created":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T08:47:09Z","timestamp":1778489229000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Comprehensive genomic profiling of vulvar squamous cell carcinoma reveals subtype-specific mutational landscapes"],"prefix":"10.1007","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8565-0798","authenticated-orcid":false,"given":"M.","family":"Choschzick","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Hoesli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Stergiou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. H.","family":"R\u00fcschoff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,11]]},"reference":[{"key":"4422_CR1","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1016\/j.semcancer.2019.07.009","volume":"59","author":"AS Alzahrani","year":"2019","unstructured":"Alzahrani AS (2019) PI3K\/Akt\/mTOR inhibitors in cancer: at the bench and bedside. Semin Cancer Biol 59:125\u2013132. https:\/\/doi.org\/10.1016\/j.semcancer.2019.07.009","journal-title":"Semin Cancer Biol"},{"key":"4422_CR2","doi-asserted-by":"publisher","first-page":"977","DOI":"10.1038\/ng.2701","volume":"45","author":"MB Burns","year":"2013","unstructured":"Burns MB, Temiz NA, Harris RS (2013) Evidence for APOBEC3B mutagenesis in multiple human cancers. Nat Genet 45:977\u2013983. https:\/\/doi.org\/10.1038\/ng.2701","journal-title":"Nat Genet"},{"key":"4422_CR3","doi-asserted-by":"publisher","unstructured":"Carreras-Dieguez N, Guerrero J, Rodrigo-Calvo MT, Ribera-Cortada I, Trias I, Jares P, Lopez Del Campo R, Saco A, Munmany M, Marimon L, Ferrando M, Vega N, Del Pino M, Torne A, Ordi J, Rakislova N (2021) Molecular landscape of vulvar squamous cell carcinoma. Int J Mol Sci 22. https:\/\/doi.org\/10.3390\/ijms22137069","DOI":"10.3390\/ijms22137069"},{"key":"4422_CR4","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1186\/s13073-017-0424-2","volume":"9","author":"ZR Chalmers","year":"2017","unstructured":"Chalmers ZR, Connelly CF, Fabrizio D, Gay L, Ali SM, Ennis R, Schrock A, Campbell B, Shlien A, Chmielecki J, Huang F, He Y, Sun J, Tabori U, Kennedy M, Lieber DS, Roels S, White J, Otto GA, Ross JS, Garraway L, Miller VA, Stephens PJ, Frampton GM (2017) Analysis of 100,000 human cancer genomes reveals the landscape of tumor mutational burden. Genome Med 9:34. https:\/\/doi.org\/10.1186\/s13073-017-0424-2","journal-title":"Genome Med"},{"key":"4422_CR5","doi-asserted-by":"publisher","DOI":"10.1097\/PGP.0000000000001077","author":"M Choschzick","year":"2024","unstructured":"Choschzick M, Gut A, Hoesli L, Stergiou C (2024) Role of immunohistochemical analysis of p16 and p53 in vulvar carcinoma. Int J Gynecol Pathol. https:\/\/doi.org\/10.1097\/PGP.0000000000001077","journal-title":"Int J Gynecol Pathol"},{"key":"4422_CR6","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1038\/s43018-020-0027-5","volume":"1","author":"A Degasperi","year":"2020","unstructured":"Degasperi A, Amarante TD, Czarnecki J, Shooter S, Zou X, Glodzik D, Morganella S, Nanda AS, Badja C, Koh G, Momen SE, Georgakopoulos-Soares I, Dias JML, Young J, Memari Y, Davies H, Nik-Zainal S (2020) A practical framework and online tool for mutational signature analyses show inter-tissue variation and driver dependencies. Nat Cancer 1:249\u2013263. https:\/\/doi.org\/10.1038\/s43018-020-0027-5","journal-title":"Nat Cancer"},{"key":"4422_CR7","doi-asserted-by":"publisher","DOI":"10.1126\/science.abl9283","author":"A Degasperi","year":"2022","unstructured":"Degasperi A, Zou X, Amarante TD, Martinez-Martinez A, Koh GCC, Dias JML, Heskin L, Chmelova L, Rinaldi G, Wang VYW, Nanda AS, Bernstein A, Momen SE, Young J, Perez-Gil D, Memari Y, Badja C, Shooter S, Czarnecki J, Brown MA, Davies HR, Genomics England Research C, Nik-Zainal S (2022) Substitution mutational signatures in whole-genome-sequenced cancers in the UK population. Science. https:\/\/doi.org\/10.1126\/science.abl9283","journal-title":"Science"},{"key":"4422_CR8","doi-asserted-by":"publisher","first-page":"1023","DOI":"10.1038\/nbt.2696","volume":"31","author":"GM Frampton","year":"2013","unstructured":"Frampton GM, Fichtenholtz A, Otto GA, Wang K, Downing SR, He J, Schnall-Levin M, White J, Sanford EM, An P, Sun J, Juhn F, Brennan K, Iwanik K, Maillet A, Buell J, White E, Zhao M, Balasubramanian S, Terzic S, Richards T, Banning V, Garcia L, Mahoney K, Zwirko Z, Donahue A, Beltran H, Mosquera JM, Rubin MA, Dogan S, Hedvat CV, Berger MF, Pusztai L, Lechner M, Boshoff C, Jarosz M, Vietz C, Parker A, Miller VA, Ross JS, Curran J, Cronin MT, Stephens PJ, Lipson D, Yelensky R (2013) Development and validation of a clinical cancer genomic profiling test based on massively parallel DNA sequencing. Nat Biotechnol 31:1023\u20131031. https:\/\/doi.org\/10.1038\/nbt.2696","journal-title":"Nat Biotechnol"},{"key":"4422_CR9","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1016\/j.gene.2017.06.056","volume":"627","author":"E Froimchuk","year":"2017","unstructured":"Froimchuk E, Jang Y, Ge K (2017) Histone H3 lysine 4 methyltransferase KMT2D. Gene 627:337\u2013342. https:\/\/doi.org\/10.1016\/j.gene.2017.06.056","journal-title":"Gene"},{"key":"4422_CR10","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1124\/molpharm.120.000006","volume":"98","author":"L Gharaibeh","year":"2020","unstructured":"Gharaibeh L, Elmadany N, Alwosaibai K, Alshaer W (2020) Notch1 in cancer therapy: possible clinical implications and challenges. Mol Pharmacol 98:559\u2013576. https:\/\/doi.org\/10.1124\/molpharm.120.000006","journal-title":"Mol Pharmacol"},{"key":"4422_CR11","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1016\/j.ygyno.2008.07.038","volume":"111","author":"WB Growdon","year":"2008","unstructured":"Growdon WB, Boisvert SL, Akhavanfard S, Oliva E, Dias-Santagata DC, Kojiro S, Horowitz NS, Iafrate AJ, Borger DR, Rueda BR (2008) Decreased survival in EGFR gene amplified vulvar carcinoma. Gynecol Oncol 111:289\u2013297. https:\/\/doi.org\/10.1016\/j.ygyno.2008.07.038","journal-title":"Gynecol Oncol"},{"key":"4422_CR12","doi-asserted-by":"publisher","first-page":"2847","DOI":"10.1093\/bioinformatics\/btw313","volume":"32","author":"Z Gu","year":"2016","unstructured":"Gu Z, Eils R, Schlesner M (2016) Complex heatmaps reveal patterns and correlations in multidimensional genomic data. Bioinformatics 32:2847\u20132849. https:\/\/doi.org\/10.1093\/bioinformatics\/btw313","journal-title":"Bioinformatics"},{"key":"4422_CR13","doi-asserted-by":"publisher","DOI":"10.1038\/emm.2017.265","volume":"50","author":"MR Han","year":"2018","unstructured":"Han MR, Shin S, Park HC, Kim MS, Lee SH, Jung SH, Song SY, Lee SH, Chung YJ (2018) Mutational signatures and chromosome alteration profiles of squamous cell carcinomas of the vulva. Exp Mol Med 50:e442. https:\/\/doi.org\/10.1038\/emm.2017.265","journal-title":"Exp Mol Med"},{"key":"4422_CR14","doi-asserted-by":"publisher","unstructured":"Horn LC, Brambs CE, Gilks B, Hoang L, Singh N, Hiller GGR, Hering K, McAlpine JN, Jamieson A, Alfaraidi M, Aktas B, Dornhofer N, Hohn AK (2024) Molecular subtypes of vulvar squamous cell carcinoma: the significance of HPV-independent\/p53 wild type. Cancers (Basel) 16. https:\/\/doi.org\/10.3390\/cancers16244216","DOI":"10.3390\/cancers16244216"},{"key":"4422_CR15","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1136\/jmedgenet-2018-105745","volume":"56","author":"J Huang","year":"2019","unstructured":"Huang J, Qian Z, Gong Y, Wang Y, Guan Y, Han Y, Yi X, Huang W, Ji L, Xu J, Su M, Yuan Q, Cui S, Zhang J, Bao C, Liu W, Chen X, Zhang M, Gao X, Wu R, Zhang Y, Xu H, Zhu S, Zhu H, Yang L, Xu X, Zhou P, Liang Z (2019) Comprehensive genomic variation profiling of cervical intraepithelial neoplasia and cervical cancer identifies potential targets for cervical cancer early warning. J Med Genet 56:186\u2013194. https:\/\/doi.org\/10.1136\/jmedgenet-2018-105745","journal-title":"J Med Genet"},{"key":"4422_CR16","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/15384047.2022.2128608","volume":"23","author":"RS Joshi","year":"2022","unstructured":"Joshi RS, Boichard A, Adashek JJ, Kurzrock R (2022) High tumor amplification burden is associated with TP53 mutations in the pan-cancer setting. Cancer Biol Ther 23:1\u20136. https:\/\/doi.org\/10.1080\/15384047.2022.2128608","journal-title":"Cancer Biol Ther"},{"key":"4422_CR17","doi-asserted-by":"publisher","first-page":"314","DOI":"10.1016\/j.ygyno.2017.05.018","volume":"146","author":"K Kashofer","year":"2017","unstructured":"Kashofer K, Regauer S (2017) Analysis of full coding sequence of the TP53 gene in invasive vulvar cancers: implications for therapy. Gynecol Oncol 146:314\u2013318. https:\/\/doi.org\/10.1016\/j.ygyno.2017.05.018","journal-title":"Gynecol Oncol"},{"key":"4422_CR18","doi-asserted-by":"publisher","first-page":"1271","DOI":"10.1177\/153537020623100713","volume":"231","author":"ES Knudsen","year":"2006","unstructured":"Knudsen ES, Knudsen KE (2006) Retinoblastoma tumor suppressor: where cancer meets the cell cycle. Exp Biol Med (Maywood) 231:1271\u20131281. https:\/\/doi.org\/10.1177\/153537020623100713","journal-title":"Exp Biol Med (Maywood)"},{"key":"4422_CR19","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1038\/s41571-022-00603-7","volume":"19","author":"M Lechner","year":"2022","unstructured":"Lechner M, Liu J, Masterson L, Fenton TR (2022) HPV-associated oropharyngeal cancer: epidemiology, molecular biology and clinical management. Nat Rev Clin Oncol 19:306\u2013327. https:\/\/doi.org\/10.1038\/s41571-022-00603-7","journal-title":"Nat Rev Clin Oncol"},{"key":"4422_CR20","first-page":"1655","volume":"9","author":"YY Lee","year":"1994","unstructured":"Lee YY, Wilczynski SP, Chumakov A, Chih D, Koeffler HP (1994) Carcinoma of the vulva: HPV and p53 mutations. Oncogene 9:1655\u20131659","journal-title":"Oncogene"},{"key":"4422_CR21","doi-asserted-by":"publisher","DOI":"10.3390\/v9080206","author":"TR Litwin","year":"2017","unstructured":"Litwin TR, Clarke MA, Dean M, Wentzensen N (2017) Somatic host cell alterations in HPV carcinogenesis. Viruses. https:\/\/doi.org\/10.3390\/v9080206","journal-title":"Viruses"},{"key":"4422_CR22","doi-asserted-by":"publisher","first-page":"18780","DOI":"10.1073\/pnas.0906357106","volume":"106","author":"X Liu","year":"2009","unstructured":"Liu X, Dakic A, Zhang Y, Dai Y, Chen R, Schlegel R (2009) HPV E6 protein interacts physically and functionally with the cellular telomerase complex. Proc Natl Acad Sci U S A 106:18780\u201318785. https:\/\/doi.org\/10.1073\/pnas.0906357106","journal-title":"Proc Natl Acad Sci U S A"},{"key":"4422_CR23","doi-asserted-by":"publisher","first-page":"16175","DOI":"10.1073\/pnas.1310432110","volume":"110","author":"ME McLaughlin-Drubin","year":"2013","unstructured":"McLaughlin-Drubin ME, Park D, Munger K (2013) Tumor suppressor p16INK4A is necessary for survival of cervical carcinoma cell lines. Proc Natl Acad Sci U S A 110:16175\u201316180. https:\/\/doi.org\/10.1073\/pnas.1310432110","journal-title":"Proc Natl Acad Sci U S A"},{"key":"4422_CR24","doi-asserted-by":"publisher","first-page":"6289","DOI":"10.1073\/pnas.92.14.6289","volume":"92","author":"RH Medema","year":"1995","unstructured":"Medema RH, Herrera RE, Lam F, Weinberg RA (1995) Growth suppression by p16ink4 requires functional retinoblastoma protein. Proc Natl Acad Sci U S A 92:6289\u20136293. https:\/\/doi.org\/10.1073\/pnas.92.14.6289","journal-title":"Proc Natl Acad Sci U S A"},{"key":"4422_CR25","doi-asserted-by":"publisher","first-page":"1016","DOI":"10.1093\/oncolo\/oyac144","volume":"27","author":"A Necchi","year":"2022","unstructured":"Necchi A, Spiess PE, Bandini M, Basile G, Grivas P, Bratslavsky G, Jacob J, Danziger N, Lin D, Decker B, Sokol ES, Huang RSP, Kulkarni SB, Ross JS (2022) Advanced squamous cell carcinomas of the pelvic and perineal region: a comprehensive genomic profiling study. Oncologist 27:1016\u20131024. https:\/\/doi.org\/10.1093\/oncolo\/oyac144","journal-title":"Oncologist"},{"key":"4422_CR26","doi-asserted-by":"publisher","first-page":"6781","DOI":"10.1158\/1078-0432.CCR-17-1302","volume":"23","author":"LS Nooij","year":"2017","unstructured":"Nooij LS, Ter Haar NT, Ruano D, Rakislova N, van Wezel T, Smit V, Trimbos B, Ordi J, van Poelgeest MIE, Bosse T (2017) Genomic characterization of vulvar (pre)cancers identifies distinct molecular subtypes with prognostic significance. Clin Cancer Res 23:6781\u20136789. https:\/\/doi.org\/10.1158\/1078-0432.CCR-17-1302","journal-title":"Clin Cancer Res"},{"key":"4422_CR27","doi-asserted-by":"publisher","first-page":"5559","DOI":"10.1128\/JVI.75.12.5559-5566.2001","volume":"75","author":"ST Oh","year":"2001","unstructured":"Oh ST, Kyo S, Laimins LA (2001) Telomerase activation by human papillomavirus type 16 E6 protein: induction of human telomerase reverse transcriptase expression through Myc and GC-rich Sp1 binding sites. J Virol 75:5559\u20135566. https:\/\/doi.org\/10.1128\/JVI.75.12.5559-5566.2001","journal-title":"J Virol"},{"key":"4422_CR28","first-page":"429","volume-title":"WHO classification of tumours of female reproductive organs","author":"J Ordi","year":"2020","unstructured":"Ordi J, Herrington CS (2020) Tumours of the vulva. In: WHO classification of tumours of female reproductive organs, 5th edn. International Agency for Research on Cancer (IARC), Lyon, pp 429\u2013434","edition":"5"},{"key":"4422_CR29","doi-asserted-by":"publisher","first-page":"1317","DOI":"10.1038\/s41379-022-01079-7","volume":"35","author":"C Parra-Herran","year":"2022","unstructured":"Parra-Herran C, Nucci MR, Singh N, Rakislova N, Howitt BE, Hoang L, Gilks CB, Bosse T, Watkins JC (2022) HPV-independent, p53-wild-type vulvar intraepithelial neoplasia: a review of nomenclature and the journey to characterize verruciform and acanthotic precursor lesions of the vulva. Mod Pathol 35:1317\u20131326. https:\/\/doi.org\/10.1038\/s41379-022-01079-7","journal-title":"Mod Pathol"},{"key":"4422_CR30","doi-asserted-by":"publisher","first-page":"274","DOI":"10.1038\/s41379-021-00942-3","volume":"35","author":"AM Salama","year":"2022","unstructured":"Salama AM, Momeni-Boroujeni A, Vanderbilt C, Ladanyi M, Soslow R (2022) Molecular landscape of vulvovaginal squamous cell carcinoma: new insights into molecular mechanisms of HPV-associated and HPV-independent squamous cell carcinoma. Mod Pathol 35:274\u2013282. https:\/\/doi.org\/10.1038\/s41379-021-00942-3","journal-title":"Mod Pathol"},{"key":"4422_CR31","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1002\/(SICI)1098-1004(1996)7:4<294::AID-HUMU2>3.0.CO;2-9","volume":"7","author":"B Smith-Sorensen","year":"1996","unstructured":"Smith-Sorensen B, Hovig E (1996) CDKN2A (p16INK4A) somatic and germline mutations. Hum Mutat 7:294\u2013303. https:\/\/doi.org\/10.1002\/(SICI)1098-1004(1996)7:4%3c294::AID-HUMU2%3e3.0.CO;2-9","journal-title":"Hum Mutat"},{"key":"4422_CR32","doi-asserted-by":"publisher","first-page":"448","DOI":"10.1038\/modpathol.2016.187","volume":"30","author":"JC Watkins","year":"2017","unstructured":"Watkins JC, Howitt BE, Horowitz NS, Ritterhouse LL, Dong F, MacConaill LE, Garcia E, Lindeman NI, Lee LJ, Berkowitz RS, Nucci MR, Crum CP (2017) Differentiated exophytic vulvar intraepithelial lesions are genetically distinct from keratinizing squamous cell carcinomas and contain mutations in PIK3CA. Mod Pathol 30:448\u2013458. https:\/\/doi.org\/10.1038\/modpathol.2016.187","journal-title":"Mod Pathol"},{"key":"4422_CR33","doi-asserted-by":"publisher","unstructured":"Williams EA, Werth AJ, Sharaf R, Montesion M, Sokol ES, Pavlick DC, McLaughlin-Drubin M, Erlich R, Toma H, Williams KJ, Venstrom JM, Alexander BM, Shah N, Danziger N, Hemmerich AC, Severson EA, Killian JK, Lin DI, Ross JS, Tse JY, Ramkissoon SH, Mochel MC, Elvin JA (2020) Vulvar squamous cell carcinoma: comprehensive genomic profiling of HPV+ versus HPV- forms reveals distinct sets of potentially actionable molecular targets. JCO Precis Oncol 4. https:\/\/doi.org\/10.1200\/PO.19.00406","DOI":"10.1200\/PO.19.00406"},{"key":"4422_CR34","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1016\/j.humpath.2019.08.003","volume":"92","author":"D Xing","year":"2019","unstructured":"Xing D, Liu Y, Park HJ, Baek I, Tran H, Cheang G, Novo J, Dillon J, Matoso A, Farmer E, Cheng MA, Tsai YC, Lombardo K, Conner MG, Vang R, Hung CF, Wu TC, Song W (2019) Recurrent genetic alterations and biomarker expression in primary and metastatic squamous cell carcinomas of the vulva. Hum Pathol 92:67\u201380. https:\/\/doi.org\/10.1016\/j.humpath.2019.08.003","journal-title":"Hum Pathol"},{"key":"4422_CR35","doi-asserted-by":"publisher","DOI":"10.1016\/j.modpat.2023.100145","volume":"36","author":"H Yang","year":"2023","unstructured":"Yang H, Almadani N, Thompson EF, Tessier-Cloutier B, Chen J, Ho J, Senz J, McConechy MK, Chow C, Ta M, Cheng A, Karnezis A, Huvila J, McAlpine JN, Gilks B, Jamieson A, Hoang LN (2023) Classification of vulvar squamous cell carcinoma and precursor lesions by p16 and p53 immunohistochemistry: considerations, caveats, and an algorithmic approach. Mod Pathol 36:100145. https:\/\/doi.org\/10.1016\/j.modpat.2023.100145","journal-title":"Mod Pathol"},{"key":"4422_CR36","doi-asserted-by":"publisher","first-page":"6172","DOI":"10.1038\/s41388-019-0872-9","volume":"38","author":"X Yuan","year":"2019","unstructured":"Yuan X, Larsson C, Xu D (2019) Mechanisms underlying the activation of TERT transcription and telomerase activity in human cancer: old actors and new players. Oncogene 38:6172\u20136183. https:\/\/doi.org\/10.1038\/s41388-019-0872-9","journal-title":"Oncogene"},{"key":"4422_CR37","doi-asserted-by":"publisher","first-page":"498","DOI":"10.1016\/j.ygyno.2020.05.034","volume":"158","author":"S Zieba","year":"2020","unstructured":"Zieba S, Chechlinska M, Kowalik A, Kowalewska M (2020) Genes, pathways and vulvar carcinoma - new insights from next-generation sequencing studies. Gynecol Oncol 158:498\u2013506. https:\/\/doi.org\/10.1016\/j.ygyno.2020.05.034","journal-title":"Gynecol Oncol"}],"container-title":["Virchows Archiv"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00428-026-04422-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00428-026-04422-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00428-026-04422-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T12:48:50Z","timestamp":1791895730000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00428-026-04422-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,11]]},"references-count":37,"alternative-id":["4422"],"URL":"https:\/\/doi.org\/10.1007\/s00428-026-04422-4","relation":{},"ISSN":["0945-6317","1432-2307"],"issn-type":[{"value":"0945-6317","type":"print"},{"value":"1432-2307","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,11]]},"assertion":[{"value":"16 October 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 January 2026","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 January 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 May 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 October 2026","order":6,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Update","order":7,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"This article was originally published under the subscription model but it is now published under an Open Access license.","order":8,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The study was approved by the local Ethics Committee (KEK-Nr.: 204-0604).","order":1,"name":"Ethics","label":"Ethics approval","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors have no relevant financial or non-financial interests to disclose.\u00a0","order":2,"name":"Ethics","label":"Conflict of interest","group":{"name":"EthicsHeading","label":"Declarations"}}]}}