{"entity":{"id":"hpv-associated-vulvar-cancer","kind":"cancer","name":"HPV-associated vulvar squamous cell carcinoma","aka":["HPV-positive vulvar cancer","p16-positive vulvar squamous cell carcinoma","Basaloid and warty vulvar carcinoma","Vulvar cancer arising from usual-type VIN"],"tldr":"HPV-associated vulvar cancer is the type of vulvar squamous cell cancer caused by persistent HPV infection, growing out of the precancer called usual-type VIN and marked by the p16 protein. It tends to affect younger women, responds better to radiotherapy and recurs less often than the HPV-independent type, and it is preventable by HPV vaccination.","summary":"The 2020 WHO classification splits vulvar squamous cell carcinoma into HPV-associated and HPV-independent disease because the two arise by different routes and behave differently. HPV-associated tumours follow persistent high-risk HPV infection, above all type 16, through the precursor high-grade squamous intraepithelial lesion (usual-type VIN), often in women who smoke or are immunosuppressed and often alongside cervical or anal HPV disease. They are basaloid or warty under the microscope, express p16 diffusely and keep wild-type p53. Large series and the AGO-CaRE-1 cohort have shown that p16-positive tumours have fewer local recurrences and better survival than p53-mutant tumours, and that they respond more completely to radiotherapy, which is why molecular subtype is now part of the pathology report even though it does not yet change first treatment.\n\nTreatment follows stage rather than subtype. Usual-type VIN is excised or treated with imiquimod, with trials of topical agents such as artesunate under way; early cancers are removed by wide local excision with sentinel node biopsy for tumours under four centimetres with more than a millimetre of invasion (GROINSS-V I), and GROINSS-V II showed that groin radiotherapy can replace lymphadenectomy when the sentinel node metastasis is two millimetres or smaller. Locally advanced disease is treated with cisplatin chemoradiotherapy (GOG 205) to avoid exenterative surgery, and recurrent or metastatic disease with carboplatin and paclitaxel, with pembrolizumab available for PD-L1-positive tumours after chemotherapy on the strength of the KEYNOTE-158 vulvar cohort. Trials now test PD-1 antibodies with lenvatinib or with the PD-1 and CTLA-4 bispecific cadonilimab in recurrent disease, and the nonavalent HPV vaccine prevents the infections that start the disease.","asOf":"2026-09-18","wikipedia":"https://en.wikipedia.org/wiki/Vulvar_cancer","links":[{"label":"GROINSS-V II (JCO 2021)","url":"https://doi.org/10.1200/JCO.21.00006"},{"label":"NCCN Vulvar Cancer","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1476"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Vulvar_cancer"}],"tags":["subtype-page","gynaecologic"],"related":["hpv-independent-vulvar-cancer","vulvar","vaginal-squamous-cell-carcinoma"],"cancers":[],"sections":[],"technologies":["sentinel-node","imrt-igrt","checkpoint-inhibitor","hpv-vaccine","precancer-ablation"],"targets":["pd1"],"drugs":["cisplatin","carboplatin","paclitaxel","bevacizumab","pembrolizumab","gardasil-9"],"companies":[],"institutions":[],"pathways":[],"terms":["hpv-p16","cps","lymphadenectomy","chemoradiation"],"trials":["nct06075264","nct04422366","nct05903833","nct05932212"],"people":[],"bottlenecks":[],"keyPapers":["paper-groinss-v-sentinel-node-vulvar-cancer-jco-2008","paper-groinss-v-ii-radiotherapy-vulvar-micrometastases-jco-2021"],"journals":[],"dependsOn":[],"notes":[],"group":"gynaecologic","burden":"Roughly a third to two fifths of vulvar squamous cell carcinomas; the commoner type in younger women and the share that HPV vaccination will eventually prevent.","subtypes":["Usual-type vulvar intraepithelial neoplasia (HPV-associated precursor, p16 positive)","Basaloid HPV-associated vulvar squamous cell carcinoma","Warty HPV-associated vulvar squamous cell carcinoma","Early-stage HPV-associated vulvar cancer (wide local excision and sentinel node)","Locally advanced HPV-associated vulvar cancer (chemoradiotherapy, radiosensitive)"],"biomarkers":["p16 immunohistochemistry (block positive) and HPV DNA","p53 immunohistochemistry (wild-type pattern)","Depth of invasion (over one millimetre triggers nodal assessment)","Sentinel node status and metastasis size (two millimetres threshold, GROINSS-V II)","PD-L1 combined positive score (pembrolizumab)","Margin status"],"standardOfCare":[{"setting":"Precursor (usual-type VIN)","approach":"Excision or laser ablation of visible lesions; imiquimod as a medical alternative; trials of artesunate ointment; HPV vaccination for prevention.","refs":["precancer-ablation","hpv-vaccine","gardasil-9","nct06075264","nct04422366"],"guideline":{"version":"NCCN Guidelines: Vulvar Cancer","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1476"}},{"setting":"Early stage (tumour under four centimetres, clinically negative groins)","approach":"Wide local excision with sentinel node biopsy (GROINSS-V I); groin radiotherapy for sentinel node metastases of two millimetres or less and lymphadenectomy for larger ones (GROINSS-V II).","refs":["sentinel-node","imrt-igrt","lymphadenectomy"],"guideline":{"version":"NCCN Guidelines: Vulvar Cancer","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1476"}},{"setting":"Locally advanced disease","approach":"Cisplatin-based chemoradiotherapy (GOG 205); surgery for residual disease; p16-positive tumours respond well.","refs":["cisplatin","imrt-igrt","chemoradiation"],"guideline":{"version":"NCCN Guidelines: Vulvar Cancer","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1476"}},{"setting":"Recurrent or metastatic disease","approach":"Carboplatin and paclitaxel with or without bevacizumab; pembrolizumab for PD-L1-positive or mismatch-repair-deficient tumours after chemotherapy; trials of pembrolizumab with lenvatinib and of cadonilimab.","refs":["carboplatin","paclitaxel","bevacizumab","pembrolizumab","nct05903833","nct05932212"],"guideline":{"version":"NCCN Guidelines: Vulvar Cancer","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1476"}}],"stateOfArt":["Molecular subtyping by p16 and p53 is now routine and predicts recurrence and radiosensitivity.","Sentinel node biopsy and radiotherapy for small node metastases have removed most groin dissections in early disease.","HPV vaccination will prevent this subtype in vaccinated cohorts."],"history":[{"year":1986,"title":"ISSVD recognises vulvar intraepithelial neoplasia as the precursor lesion","refs":["hpv-p16"]},{"year":2008,"title":"GROINSS-V I: sentinel node biopsy is safe in early vulvar cancer","refs":["sentinel-node"]},{"year":2020,"title":"WHO classification divides vulvar squamous cell carcinoma into HPV-associated and HPV-independent types","refs":["hpv-p16"]},{"year":2021,"title":"GROINSS-V II: radiotherapy replaces lymphadenectomy for sentinel node metastases of two millimetres or less","refs":["sentinel-node","imrt-igrt"]},{"year":2022,"title":"Pembrolizumab responses reported in the KEYNOTE-158 vulvar cohort","refs":["pembrolizumab"]}],"pipeline":["pembrolizumab","nct05903833","nct05932212","nct06075264","hpv-vaccine"],"openProblems":["No treatment yet differs by HPV status despite the difference in behaviour.","Recurrence of usual-type VIN after treatment is common.","Checkpoint inhibitors help only a minority in recurrent disease.","Vulvar cancer is too rare for large randomised trials, so most evidence is borrowed from cervical cancer."],"parent":"vulvar"},"route":"/cancers/hpv-associated-vulvar-cancer/","neighbours":{"cancer":[{"id":"hpv-independent-vulvar-cancer","kind":"cancer","name":"HPV-independent vulvar squamous cell carcinoma (p53-mutant)","route":"/cancers/hpv-independent-vulvar-cancer/"},{"id":"vaginal-squamous-cell-carcinoma","kind":"cancer","name":"Vaginal squamous cell carcinoma (HPV-associated)","route":"/cancers/vaginal-squamous-cell-carcinoma/"},{"id":"vulvar","kind":"cancer","name":"Vulvar cancer","route":"/cancers/vulvar/"}],"technology":[{"id":"hpv-vaccine","kind":"technology","name":"HPV & HBV vaccination","route":"/technologies/hpv-vaccine/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"},{"id":"imrt-igrt","kind":"technology","name":"IMRT / IGRT (modern external beam)","route":"/technologies/imrt-igrt/"},{"id":"sentinel-node","kind":"technology","name":"Sentinel lymph node biopsy","route":"/technologies/sentinel-node/"},{"id":"precancer-ablation","kind":"technology","name":"Thermal ablation and cryotherapy for cervical precancer","route":"/technologies/precancer-ablation/"}],"target":[{"id":"pd1","kind":"target","name":"PD-1","route":"/targets/pd1/"}],"drug":[{"id":"bevacizumab","kind":"drug","name":"Bevacizumab","route":"/drugs/bevacizumab/"},{"id":"carboplatin","kind":"drug","name":"Carboplatin","route":"/drugs/carboplatin/"},{"id":"cisplatin","kind":"drug","name":"Cisplatin","route":"/drugs/cisplatin/"},{"id":"gardasil-9","kind":"drug","name":"Nonavalent HPV vaccine","route":"/drugs/gardasil-9/"},{"id":"paclitaxel","kind":"drug","name":"Paclitaxel / nab-paclitaxel","route":"/drugs/paclitaxel/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}],"term":[{"id":"chemoradiation","kind":"term","name":"Chemoradiation (chemoradiotherapy, CRT)","route":"/terms/chemoradiation/"},{"id":"cps","kind":"term","name":"Combined positive score (CPS)","route":"/terms/cps/"},{"id":"hpv-p16","kind":"term","name":"HPV-positive (p16) head and neck cancer","route":"/terms/hpv-p16/"},{"id":"lymphadenectomy","kind":"term","name":"Lymphadenectomy (lymph node dissection)","route":"/terms/lymphadenectomy/"}],"trial":[{"id":"nct05932212","kind":"trial","name":"AK104 for Recurrent or Metastatic Vulvar Cancer","route":"/trials/nct05932212/"},{"id":"nct04422366","kind":"trial","name":"Evaluate the Efficacy, Immunogenicity and Safety of 9-valent HPV Recombinant Vaccine in Chinese Healthy Females","route":"/trials/nct04422366/"},{"id":"nct05903833","kind":"trial","name":"Pembrolizumab Combination With Lenvatinib in Pts With Recurrent,Persistent,Metastatic or Locally Advanced Vulvar Cancer Not Amenable to Curative Surge","route":"/trials/nct05903833/"},{"id":"nct06075264","kind":"trial","name":"Phase II Study of Artesunate Ointment for the Treatment of Vulvar High Grade Squamous Intraepithelial Lesions (Vulvar HSIL, VIN2/3)","route":"/trials/nct06075264/"}],"paper":[{"id":"paper-groinss-v-ii-radiotherapy-vulvar-micrometastases-jco-2021","kind":"paper","name":"GROINSS-V II: radiotherapy versus inguinofemoral lymphadenectomy for vulvar cancer with sentinel node micrometastases","route":"/key-papers/paper-groinss-v-ii-radiotherapy-vulvar-micrometastases-jco-2021/"},{"id":"paper-groinss-v-sentinel-node-vulvar-cancer-jco-2008","kind":"paper","name":"GROINSS-V: sentinel node dissection is safe in early-stage vulvar cancer","route":"/key-papers/paper-groinss-v-sentinel-node-vulvar-cancer-jco-2008/"}]}}