Vaginal squamous cell carcinoma (HPV-associated)
Vaginal squamous cell carcinoma is the commonest form of vaginal cancer, caused by the same HPV infection as cervical cancer and often following earlier cervical disease. It is treated much as cervical cancer is, with radiotherapy, brachytherapy and cisplatin for most stages and surgery only for small upper-vaginal tumours, and it is prevented by HPV vaccination and cervical screening.
Overview
Squamous cell carcinoma makes up most primary vaginal cancers and shares its cause and precursor with cervical cancer: persistent high-risk HPV infection leading to vaginal intraepithelial neoplasia (VAIN), which is commonest at the vaginal vault after hysterectomy for cervical precancer. The strict definition excludes tumours that reach the cervix or vulva, which are classified as cervical or vulvar, and metastases from the cervix, endometrium and bowel outnumber true primaries. Diagnosis is by biopsy at colposcopy, staging is clinical and by MRI and PET-CT under the FIGO system shared with cervical cancer, and p16 confirms HPV association.
Because the disease is rare, no randomised trial has ever been run in it, and treatment is extrapolated from cervical cancer. High-grade VAIN is treated with laser ablation, excision, topical imiquimod or fluorouracil, or brachytherapy for extensive vault disease. Small stage I tumours of the upper vagina can be removed by radical upper vaginectomy with pelvic lymphadenectomy, but most patients receive external beam radiotherapy to the pelvis and groins followed by brachytherapy, with concurrent weekly cisplatin for stage II and above by analogy with cervical chemoradiotherapy; brachytherapy dose is the strongest determinant of local control. Recurrent or metastatic disease is treated as cervical cancer, with carboplatin and paclitaxel with or without bevacizumab and with pembrolizumab for PD-L1-positive tumours, extrapolating KEYNOTE-826. HPV vaccination and cervical screening prevent the disease, and Chinese vaccine trials list vaginal cancer among their endpoints.
State of the art
- Image-guided brachytherapy gives high local control in stage I and II disease.
- Chemoradiotherapy is standard for stage II and above by extrapolation from cervical cancer.
- HPV vaccination and cervical screening are preventing the disease in younger cohorts.
Red cards
From the labels and guidelines behind the standard of care. Your team's thresholds win.- Emergency services nowBleeding or bruising
Bleeding that will not stop, black or bloody stools, or unexplained bruising when platelets are expected to be low.
- Emergency services nowBlood clot (lenalidomide, pomalidomide, thalidomide)
A swollen painful calf, or sudden breathlessness with chest pain; venous and arterial thromboembolism is a boxed warning and blood-thinning prophylaxis is recommended.
- Emergency services nowHypophysitis or adrenal crisis
Persistent headache with extreme tiredness, nausea, dizziness on standing or low blood pressure. Vomiting, severe weakness or collapse is adrenal crisis.
- Check before combiningFood and drink: Fluorouracil (5-FU)
Capecitabine: take within 30 minutes after a meal. DPD deficiency (DPYD variants) causes severe toxicity: pre-treatment genotyping is recommended in Europe.
- Check before combiningFood and drink: Pembrolizumab
No pharmacokinetic interactions expected (antibody). See the irAE guide for toxicity management.
- Check before combiningKidneys: Carboplatin
Dose by Calvert formula using GFR (see the calculators).
See all on the product pages:CarboplatinCisplatinFluorouracil (5-FU)Paclitaxel / nab-paclitaxelPembrolizumab·Printable cards in the navigator
Anatomy and lymph node drainage
- Fallopian tube fimbria (origin of high-grade serous)
- Ovary (other histologies, germ cell)
- Endometrium
- Myometrium (uterine sarcoma)
- Placental site (gestational trophoblastic)
- Cervix, transformation zone
- Vulva
- Nodes: obturator and external iliac
- Nodes: internal iliac
- Nodes: para-aortic (ovary, high uterus)
- Nodes: inguinal (vulva)
Most high-grade ovarian cancers begin at the tip of the fallopian tube; endometrial cancer lines the uterus, cervical cancer starts at the transformation zone; each drains to a different node group.
- Fallopian tube fimbria (origin of high-grade serous)
- Ovary (other histologies, germ cell)
- EndometriumHigh-grade vaginal intraepithelial neoplasia (VAIN 2 to 3, precursor, often at the vault after hysterectomy)
- Myometrium (uterine sarcoma)
- Placental site (gestational trophoblastic)
- Cervix, transformation zoneHigh-grade vaginal intraepithelial neoplasia (VAIN 2 to 3, precursor, often at the vault after hysterectomy) · Stage I vaginal squamous cell carcinoma (upper vagina, surgery or brachytherapy) · Stage II to IVA vaginal squamous cell carcinoma (chemoradiotherapy with brachytherapy) · HPV-associated vaginal cancer after cervical precancer · Recurrent or metastatic vaginal squamous cell carcinoma (treated as cervical cancer)
- VulvaHPV-associated vaginal cancer after cervical precancer
- obturator and external iliac
- internal iliac
- para-aortic (ovary, high uterus)
- inguinal (vulva)
Same organ: High-grade serous ovarian cancer, Low-grade serous ovarian cancer, Clear cell ovarian cancer, Mucinous ovarian cancer, Adult granulosa cell tumour of the ovary, Ovarian cancer, Endometrial cancer, Cervical cancer, Vulvar cancer, Gestational trophoblastic neoplasia, Uterine sarcoma, Vaginal cancer, POLE-ultramutated endometrial cancer, Mismatch-repair-deficient endometrial cancer, p53-abnormal endometrial cancer, including uterine serous carcinoma, Endometrial cancer with no specific molecular profile, Advanced or recurrent endometrial cancer, Uterine carcinosarcoma, Early cervical cancer and fertility-sparing surgery, Locally advanced cervical cancer, Recurrent or metastatic cervical cancer, Platinum-sensitive ovarian cancer, Platinum-resistant ovarian cancer, HPV-associated vulvar squamous cell carcinoma, HPV-independent vulvar squamous cell carcinoma (p53-mutant), Vaginal adenocarcinoma (including DES-associated clear cell adenocarcinoma), Low-risk gestational trophoblastic neoplasia (FIGO score 0 to 6), High-risk gestational trophoblastic neoplasia (FIGO score 7 or more, including ultra-high-risk), Placental-site trophoblastic tumour and epithelioid trophoblastic tumour
The large majority of primary vaginal cancers, mostly in women over 60, many with a history of cervical precancer or hysterectomy for it; a tumour is called vaginal only when the cervix and vulva are uninvolved.
- HPV & HBV vaccinationStandard of care
- HPV DNA testing and self-samplingStandard of care
Nothing recorded yet.
Nothing recorded yet.
Also on OnCo: Symptoms and red flags · Early detection roadmap.
Cases by country
No country-level case numbers. This cancer is not mapped to a GLOBOCAN site.
One section per setting: the options named, what each is for, the trials behind them, the recorded trade-offs and the questions to ask.
Laser ablation or excision; topical imiquimod or fluorouracil; brachytherapy for extensive vault disease; HPV vaccination and screening for prevention.
Radical upper vaginectomy with pelvic lymphadenectomy, or brachytherapy with or without external beam radiotherapy.
External beam radiotherapy to the pelvis (and groins for lower-third tumours) with concurrent weekly cisplatin, followed by brachytherapy, extrapolating from cervical cancer.
Carboplatin and paclitaxel with or without bevacizumab; pembrolizumab for PD-L1-positive tumours (KEYNOTE-826 extrapolated); pelvic exenteration for isolated central recurrence after radiotherapy.
Subtypes & biomarkers
top- High-grade vaginal intraepithelial neoplasia (VAIN 2 to 3, precursor, often at the vault after hysterectomy)
- Stage I vaginal squamous cell carcinoma (upper vagina, surgery or brachytherapy)
- Stage II to IVA vaginal squamous cell carcinoma (chemoradiotherapy with brachytherapy)
- HPV-associated vaginal cancer after cervical precancer
- Recurrent or metastatic vaginal squamous cell carcinoma (treated as cervical cancer)
- HPV DNA and p16 immunohistochemistry
- FIGO stage (clinical, MRI, PET-CT)
- Prior cervical neoplasia or hysterectomy
- PD-L1 combined positive score (pembrolizumab, extrapolated)
- Brachytherapy dose delivered (local control)
How often this target appears
- 1933Vaginal intraepithelial neoplasia first described
- 1999Cisplatin chemoradiotherapy becomes standard in cervical cancer and is adopted for vaginal cancer
- 2006HPV vaccine approved with protection against vaginal precancer
- 2021KEYNOTE-826 adds pembrolizumab to first-line therapy in cervical cancer, extrapolated to vaginal cancer
Dated changes read from the records linked to this cancer: approvals, regulatory steps, reported trials, guideline versions and milestones. Newest first; no date is inferred.
All 6 changes by month →- 2026-09-18This recordVaginal squamous cell carcinoma (HPV-associated)Facts on this page last checked
When this page itself was last checked or edited.
- 2021Trial resultKEYNOTE-826KEYNOTE-826 reported
OS 26.
- 2021MilestonePembrolizumabKEYNOTE-826 adds pembrolizumab to first-line therapy in cervical cancer, extrapolated to vaginal cancer
A milestone in how this cancer is treated.
- 2006MilestoneHPV & HBV vaccinationHPV vaccine approved with protection against vaginal precancer
A milestone in how this cancer is treated.
- 1999MilestoneCisplatinCisplatin chemoradiotherapy becomes standard in cervical cancer and is adopted for vaginal cancer
A milestone in how this cancer is treated.
- 1933MilestoneVaginal squamous cell carcinoma (HPV-associated)Vaginal intraepithelial neoplasia first described
A milestone in how this cancer is treated.
What is in development for Vaginal squamous cell carcinoma (HPV-associated), drawn from the whole corpus: 2 items. Drugs are grouped by the most advanced trial phase they have reached anywhere; approved treatments sit under standard of care. Technologies are the methods being tested for this cancer, trials are the studies recorded here, and ideas are proposals not yet in a trial.
Trials under way · 2
- Phase II Study of Dysplasix™ Intravaginal Suppositories in Patients Patients With High-Risk HPV and Mild Cervical Cytologic Abnormalities · phase 2 · Amplexd Therapeutics, Inc.
- Evaluate the Efficacy, Immunogenicity and Safety of 9-valent HPV Recombinant Vaccine in Chinese Healthy Females · phase 3 · Shanghai Bovax Biotechnology Co., Ltd.
Open problems and what is being done
No randomised trial has ever been conducted in vaginal cancer.
Radiotherapy causes vaginal stenosis and sexual morbidity that are poorly addressed.
and how the field plans to fix it →What is being done about thisSide effects and quality of lifeAvailable now- Immune checkpoint inhibitorsStandard of care
- IMRT / IGRT (modern external beam)Standard of care
In trialsNothing recorded yet.
Ideas and roadmapsNothing recorded yet.
Also on OnCo: Side effects by symptom · Immune-related side effects · Toxicity compare · Survivorship planner.
The role of chemotherapy with radiotherapy is assumed, not proven.
Tumours at the vault after hysterectomy are hard to distinguish from recurrent cervical cancer.
Trials
topTrials recruiting now
Country and place are remembered in this browser only. A postcode is sent to OpenStreetMap's Nominatim service to find coordinates when you press the button; nothing else leaves your device.
Landmark trials
Expert centres
topExpert centres
Baltimore · cancer center | United States | 0 | 2,955 | 41,449 | #10 | ||
Wuhan · hospital | China | none recorded | 0 | 2,478 | 31,527 | - | |
Heidelberg · research institute | Germany | none recorded | 0 | 2,202 | 32,575 | - | |
New Delhi · government | India | none recorded | 0 | 2,028 | 15,043 | - | |
Utrecht · cancer center | Netherlands | none recorded | 0 | 1,422 | 20,323 | - | |
Bethesda, MD · government | United States | none recorded | 0 | 1,312 | 26,262 | - | |
Leiden · university | Netherlands | none recorded | 0 | 1,245 | 16,125 | - | |
Tianjin · cancer center | China | none recorded | 0 | 1,219 | 11,455 | - | |
Hangzhou · cancer center | China | none recorded | 0 | 1,219 | 17,635 | - | |
Rozzano (Milan) · hospital | Italy | none recorded | 0 | 1,031 | 10,720 | - | |
L'Hospitalet de Llobregat · cancer center | Spain | 0 | 988 | 14,310 | - | ||
Changsha · cancer center | China | none recorded | 0 | 930 | 14,477 | - | |
Jinan · cancer center | China | none recorded | 0 | 920 | 7,804 | - | |
Oakland, CA · research institute | United States | none recorded | 0 | 908 | 10,296 | - | |
New Delhi · hospital | India | none recorded | 0 | 880 | 5,143 | - |
These are the things we can measure; they are not a ranking of quality. Each column is a field on the institution record or a count over what OnCo has linked; a centre that treats many patients with Vaginal squamous cell carcinoma but is thinly recorded here will look small.
Not known: OnCo holds no case-volume or outcome figures for centres, so none are shown. Where a national audit or registry publishes them, the centre's page links to it. Default order: Newsweek rank, then trials for this cancer, then research output.
Questions to ask
topQuestions to ask your oncologist about Vaginal squamous cell carcinoma
Newly diagnosed
- What is my exact diagnosis, stage, and grade, and which tests established them?Why: Everything else follows from an accurate stage and subtype.
- Which biomarkers have been tested on my tumour (for example HPV DNA and p16 immunohistochemistry, FIGO stage, Prior cervical neoplasia or hysterectomy, PD-L1 combined positive score, Brachytherapy dose delivered), and what were the results?Why: These results decide eligibility for targeted therapy, immunotherapy, and trials.
- Which subtype is my cancer, and does that change the recommended treatment?Why: Recognised subtypes for this cancer include High-grade vaginal intraepithelial neoplasia, Stage I vaginal squamous cell carcinoma, Stage II to IVA vaginal squamous cell carcinoma.
- Is germline (inherited) genetic testing recommended for me or my family?Why: Inherited variants can change treatment and matter for relatives.
Precursor (VAIN)
- For my situation (precursor (vain)), which of the standard options do you recommend and why?Why: Guideline options include: Laser ablation or excision; topical imiquimod or fluorouracil; brachytherapy for extensive vault disease; HPV vaccination and screening for prevention.
- Am I a candidate for Fluorouracil (5-FU), Nonavalent HPV vaccine, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of Evaluate the Efficacy, Immunogenicity and Safety of 9-valent HPV Recombinant Vaccine in Chinese Healthy Females and Immunogenicity and Safety of Quadrivalent HPV Vaccine in Healthy Chinese Female Subjects Aged 9 to 19 Years apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
Stage I, upper vagina
- For my situation (stage i, upper vagina), which of the standard options do you recommend and why?Why: Guideline options include: Radical upper vaginectomy with pelvic lymphadenectomy, or brachytherapy with or without external beam radiotherapy.
Stage II to IVA
- For my situation (stage ii to iva), which of the standard options do you recommend and why?Why: Guideline options include: External beam radiotherapy to the pelvis (and groins for lower-third tumours) with concurrent weekly cisplatin, followed by brachytherapy, extrapolating from cervical cancer.
- Am I a candidate for Cisplatin, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Recurrent or metastatic disease
- For my situation (recurrent or metastatic disease), which of the standard options do you recommend and why?Why: Guideline options include: Carboplatin and paclitaxel with or without bevacizumab; pembrolizumab for PD-L1-positive tumours (KEYNOTE-826 extrapolated); pelvic exenteration for isolated central recurrence after radiotherapy.
- Am I a candidate for Carboplatin, Paclitaxel / nab-paclitaxel, Pembrolizumab, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of KEYNOTE-826 apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
Any stage
- Are there clinical trials I could join, for example of Pembrolizumab, HPV & HBV vaccination, Phase II Study of Dysplasix™ Intravaginal Suppositories in Patients Patients With High-Risk HPV and Mild Cervical Cytologic Abnormalities?Why: Trials are how the next standard of care is set; asking early keeps options open.
- Would a second opinion at a high-volume centre change anything, and can you help arrange it?Why: Rare or high-stakes decisions benefit from a centre that treats many similar patients.
- What supportive care (symptom control, nutrition, exercise, mental health, financial help) is available from the start?Why: Supportive care improves quality of life and helps patients complete treatment.
- I read that “No randomised trial has ever been conducted in vaginal cancer”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
- I read that “Radiotherapy causes vaginal stenosis and sexual morbidity that are poorly addressed”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
Newly diagnosed? Read the first 60 days with Vaginal squamous cell carcinoma, then print the one-page appointment sheet with room for the answers.
Print this page for your appointment (your browser's print command). These prompts are for discussion; your clinical team knows your case.
Direct links plus the targets, companies, and technologies of this cancer's products.
technologies
9targets
2drugs
6companies
4terms
5trials
4key papers
2The treatment pathway on the vaginal cancer pages, radiotherapy with brachytherapy and cisplatin sensitisation for locally advanced disease, follows this report.
Because primary vaginal cancer is too rare for randomised trials, staging and prognosis rest on registry reports like this one, and treatment is extrapolated from cervical cancer.
Latest papers
topQuery for this cancer: (TITLE:"Vaginal squamous cell carcinoma" OR ABSTRACT:"Vaginal squamous cell carcinoma" OR TITLE:"HPV-associated" OR ABSTRACT:"HPV-associated" OR TITLE:"Primary vaginal squamous cell carcinoma" OR ABSTRACT:"Primary vaginal squamous cell carcinoma" OR TITLE:"HPV-related vaginal cancer" OR ABSTRACT:"HPV-related vaginal cancer" OR TITLE:"Vaginal cancer treated with chemoradiotherapy" OR ABSTRACT:"Vaginal cancer treated with chemoradiotherapy" OR TITLE:"VAIN and vaginal squamous carcinoma" OR ABSTRACT:"VAIN and vaginal squamous carcinoma") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Vaginal squamous cell carcinoma (HPV-associated), not a curated reading list.
Similar pages
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Shares HPV status (HPV-positive / HPV-negative), Lymphadenectomy (lymph node dissection), HPV-positive (p16) head and neck cancer, Fluorouracil (5-FU) and the tag subtype-page.