Vaginal cancer
Primary vaginal cancer is rare and mostly caused by HPV, the virus behind cervical cancer. It is treated like cervical cancer, with chemotherapy given alongside external and internal radiotherapy, which cures many patients while preserving the organ. HPV vaccination and cervical screening, which also detects vaginal precursors, are steadily reducing it.
Overview
Primary vaginal carcinoma is defined as a tumour confined to the vagina without involvement of the cervix or vulva; tumours touching either are classified as cervical or vulvar. Most are HPV-related squamous cell carcinomas arising from vaginal intraepithelial neoplasia (VAIN), often in women with prior cervical neoplasia or hysterectomy for CIN. Adenocarcinoma is uncommon: clear cell adenocarcinoma in young women was the signature harm of in-utero diethylstilboestrol (DES) exposure between the 1940s and 1971, and the cohort is now ageing out. Melanoma and, in young children, embryonal rhabdomyosarcoma (sarcoma botryoides) complete the differential.
Because randomised trials are impossible at this rarity, treatment is extrapolated from cervical cancer. Small stage I lesions of the upper vagina can be excised or treated with brachytherapy alone; most patients receive definitive external beam radiotherapy with concurrent weekly cisplatin followed by image-guided brachytherapy, which preserves the vagina and gives local control comparable to cervical cancer series. Radical surgery (vaginectomy, exenteration) is reserved for radiotherapy failures or selected early lesions. Metastatic or recurrent disease is treated with platinum-based chemotherapy and, since 2018 for PD-L1-positive HPV-associated tumours by extension from cervical data, pembrolizumab; the KEYNOTE-A18 chemoradiation-plus-pembrolizumab result in cervical cancer is being extrapolated to locally advanced vaginal cancer. VAIN is treated with laser, topical imiquimod or fluorouracil, or excision, and surveillance after hysterectomy for CIN 3 is recommended.
Prevention rests on HPV vaccination and on cervical screening programmes, which detect VAIN incidentally.
State of the art today
- Chemoradiation with image-guided brachytherapy gives high local control while preserving the vagina; it is the standard by extrapolation from cervical cancer.
- Checkpoint inhibitors approved for cervical cancer are being applied to HPV-associated vaginal cancer; dedicated cohorts in HPV-basket trials are recruiting.
- HPV vaccination and cervical screening are shrinking the disease; DES-associated clear cell cancers are disappearing as the exposed cohort ages.
Show survival figures (1)
Averages across everyone diagnosed, often years ago. Your stage, subtype, age, fitness and the treatment you receive matter more than the average, and the numbers are improving quickly.
- Survivorship issues (vaginal stenosis, sexual function, bladder and bowel toxicity) are addressed with dilator programmes and MRI-guided adaptive brachytherapy.
Where it starts and where it drains
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)Adenocarcinoma (including DES-associated clear cell adenocarcinoma)
- Endometrium
- Myometrium (uterine sarcoma)Embryonal rhabdomyosarcoma (children; see rhabdomyosarcoma)
- Placental site (gestational trophoblastic)
- Cervix, transformation zoneSquamous cell carcinoma (HPV-associated; most) · Adenocarcinoma (including DES-associated clear cell adenocarcinoma) · Vaginal melanoma · VAIN 1 to 3 (precursor)
- VulvaSquamous cell carcinoma (HPV-associated; most) · Vaginal melanoma
- obturator and external iliac
- internal iliac
- para-aortic (ovary, high uterus)
- inguinal (vulva)
Same organ: Ovarian cancer, Endometrial cancer, Cervical cancer, Vulvar cancer, Gestational trophoblastic neoplasia, Uterine sarcoma
About one to two percent of gynaecological cancers; most vaginal tumours are actually spread from the cervix, vulva or endometrium, and true primary vaginal cancer is rare (SEER).
- HPV & HBV vaccinationStandard of care
- HPV DNA testing and self-samplingStandard of care
- AI in radiologyEstablished
- cfDNA fragmentomicsEstablished
- Colorectal cancer screening (colonoscopy, FIT, stool DNA, blood)Standard of care
- DNA methylation profilingEstablished
- A 28-day national pathway for people with a positive multi-cancer blood test
- A breath test to rule out cancer in people with vague symptoms
- A cancer blood test for older people arriving at A&E with unexplained symptoms
- A legislated, publicly reported 28-day standard from urgent referral to diagnosis
- A live national dashboard of stage at diagnosis as the scorecard for early detection
- A single 'cancer check at 60' appointment bundling all screening tests
Background: Alpha-fetoprotein (AFP), Barrett's oesophagus, CA 19-9, Early detection, Faecal immunochemical test (FIT). Also on OnCo: Symptoms and red flags · Early detection roadmap.
Where the cases are
No country-level case numbers. This cancer is not mapped to a GLOBOCAN site.
Laser ablation, topical imiquimod or fluorouracil, or excision; surveillance after treatment of CIN 3 or hysterectomy for CIN.
Wide excision or brachytherapy alone in selected cases.
External beam radiotherapy with concurrent weekly cisplatin followed by image-guided brachytherapy, extrapolated from cervical cancer.
Platinum-based chemotherapy; pembrolizumab for PD-L1-positive disease by extension from cervical cancer; salvage exenterative surgery for isolated central recurrence after radiotherapy.
Subtypes & biomarkers
top- Squamous cell carcinoma (HPV-associated; most)
- Adenocarcinoma (including DES-associated clear cell adenocarcinoma)
- Vaginal melanoma
- Embryonal rhabdomyosarcoma (children; see rhabdomyosarcoma)
- VAIN 1 to 3 (precursor)
- HPV DNA / p16 IHC
- FIGO stage (clinical, MRI and PET-CT)
- PD-L1 CPS (checkpoint inhibitor eligibility, extrapolated from cervical cancer)
- Prior cervical neoplasia or hysterectomy history
- DES exposure history (clear cell adenocarcinoma)
Target prevalence in this cancer
- 1971DES linked to vaginal clear cell adenocarcinoma
Herbst and colleagues (NEJM 1971) report the association; DES is withdrawn for pregnancy the same year.
- 1999Cisplatin chemoradiation becomes the cervical cancer standard
Five randomised trials; the approach is extrapolated to vaginal cancer.
- 2006HPV vaccine approved
Protects against the HPV types that cause most vaginal, cervical and vulvar cancers.
- 2018Pembrolizumab approved for PD-L1-positive cervical cancer
Extended in practice to HPV-associated vaginal cancer.
- 2023ESGO / ESTRO / ESP guidance on rare gynaecological cancers includes vaginal cancer
Open problems, and what is being done about each
No dedicated randomised trials; HPV-basket immunotherapy trials and international rare-tumour registries are filling the gap.
and how the field plans to fix it →What is being done about thisRare cancers and small trialsAvailable now- AI trial matching & clinical decision supportEstablished
- Comprehensive genomic profilingStandard of care
- Dinutuximab (ch14.18) / dinutuximab betaApproved
- Eflornithine (DFMO)Approved
- LarotrectinibApproved
- Limb-salvage surgery and endoprosthetic reconstructionStandard of care
In trials- ACTIONRecruiting
- COG AALL1731Positive
- COG ANBL0032Positive
- DeFiPositive
- Euro Ewing 2012Positive
- Functional (ex vivo) drug testingEmerging
Ideas and roadmaps- A digital second-opinion network answering community oncologists within 72 hours
- A DRUP-style protocol for off-label generic targeted drugs in rare tumours
- A funded expert second opinion for every new high-stakes or rare cancer diagnosis
- A global first-in-human network for academic cancer trials with single ethics review
- A global open trials operating system any hospital can plug into
- A live 'seats available' feed for trial slots, like airline inventory
Background: Basket, umbrella, and platform trials, Centralisation and high-volume centres, FNCLCC grade (soft-tissue sarcoma), Histotype-tailored therapy, INRG staging and risk groups. Also on OnCo: Find a trial · Expert centres.
Optimal brachytherapy technique and dose for vaginal primaries; MRI-guided adaptive brachytherapy series are maturing.
Late toxicity and sexual function after pelvic radiotherapy; survivorship programmes are the response.
and how the field plans to fix it →What is being done about thisSide effects and quality of lifeAvailable now- IMRT / IGRT (modern external beam)Standard of care
- Cardio-oncologyEstablished
- Exercise & lifestyle oncologyEstablished
- Geriatric assessmentEstablished
- Oncology nutrition assessment and medical nutrition therapyEstablished
- Proton therapyEstablished
In trialsIdeas and roadmaps- A cheap old tablet to restore appetite
- A coordinated FLASH radiotherapy evidence programme with shared dose-rate standards
- A dedicated programme for cachexia and treatment toxicity research
- A dietitian in every gastrointestinal and head and neck tumour board
- A funded programme of organ-preservation trials to avoid radical surgery
- A lifelong late-effects registry linked to every treatment for adult survivors
Background: CTCAE toxicity grading (grade 3-4 adverse events), De-escalation, escalation and response-adapted therapy, Immune-related adverse events (irAEs), Quality of life, Toxicity grade. Also on OnCo: Side effects, symptom first · Immune-related side effects · Toxicity compare · Survivorship planner.
Surveillance of women treated for CIN 3 to catch VAIN early.
Trials
topRecruiting now (live from ClinicalTrials.gov)
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Landmark trials in OnCo
Expert centres
topCentres linked to this cancer in OnCo
- Johns Hopkins Hospital / Sidney Kimmel Comprehensive Cancer CenterBaltimore, USNewsweek oncology #10NCI comprehensivevia Pembrolizumab
- Institut National d'Oncologie, RabatRabat, MAvia HPV & HBV vaccination, Brachytherapy, IMRT / IGRT (modern external beam)
- Institute of Oncology LjubljanaLjubljana, SIvia HPV & HBV vaccination, Brachytherapy, IMRT / IGRT (modern external beam)
- Kenyatta National HospitalNairobi, KEvia HPV & HBV vaccination, Brachytherapy, IMRT / IGRT (modern external beam)
- Ocean Road Cancer InstituteDar es Salaam, TZvia HPV & HBV vaccination, Brachytherapy, IMRT / IGRT (modern external beam)
- American Society for Radiation OncologyArlington, VA, USvia Brachytherapy, IMRT / IGRT (modern external beam)
- Cancer Institute (WIA), AdyarChennai, INvia HPV & HBV vaccination, Brachytherapy
- Centre Oscar LambretLille, FRvia Brachytherapy, IMRT / IGRT (modern external beam)
- via HPV & HBV vaccination, IMRT / IGRT (modern external beam)
- Dharmais National Cancer CenterJakarta, IDvia HPV & HBV vaccination, Brachytherapy
- European Society for Radiotherapy and OncologyBrussels, BEvia Brachytherapy, IMRT / IGRT (modern external beam)
- GOG FoundationPhiladelphia, PA, USvia Pembrolizumab, KEYNOTE-A18 / ENGOT-cx11 / GOG-3047
- Groote Schuur Hospital / University of Cape TownCape Town, ZAvia Brachytherapy, IMRT / IGRT (modern external beam)
- Hacettepe University Cancer InstituteAnkara, TRvia Brachytherapy, IMRT / IGRT (modern external beam)
- Ho Chi Minh City Oncology HospitalHo Chi Minh City, VNvia Brachytherapy, IMRT / IGRT (modern external beam)
- via HPV & HBV vaccination, HPV DNA testing and self-sampling
- Institut BergoniéBordeaux, FRvia Brachytherapy, IMRT / IGRT (modern external beam)
- Institut Salah AzaïezTunis, TNvia Brachytherapy, IMRT / IGRT (modern external beam)
- via HPV & HBV vaccination, Brachytherapy
- Instituto Nacional de Cancerología (Mexico)Mexico City, MXvia HPV & HBV vaccination, Brachytherapy
- via HPV & HBV vaccination, Brachytherapy
- via Brachytherapy, IMRT / IGRT (modern external beam)
- Istanbul University Institute of OncologyIstanbul, TRvia Brachytherapy, IMRT / IGRT (modern external beam)
- Korle Bu Teaching HospitalAccra, GHvia Brachytherapy, IMRT / IGRT (modern external beam)
- Lagos University Teaching HospitalLagos, NGvia Brachytherapy, IMRT / IGRT (modern external beam)
- via Brachytherapy, IMRT / IGRT (modern external beam)
- via Brachytherapy, IMRT / IGRT (modern external beam)
- National Institute of Oncology, HungaryBudapest, HUvia Brachytherapy, IMRT / IGRT (modern external beam)
- Society of Gynecologic OncologyChicago, IL, USvia KEYNOTE-A18 / ENGOT-cx11 / GOG-3047, HPV & HBV vaccination
- Uganda Cancer InstituteKampala, UGvia HPV & HBV vaccination, Brachytherapy
- via HPV & HBV vaccination, HPV DNA testing and self-sampling
- Velindre Cancer CentreCardiff, GBvia Brachytherapy, IMRT / IGRT (modern external beam)
- Aarhus University HospitalAarhus, DKvia IMRT / IGRT (modern external beam)
- All India Institute of Medical Sciences, New DelhiNew Delhi, INvia HPV & HBV vaccination
- Alliance for Clinical Trials in OncologyChicago, IL, USvia Pembrolizumab
- BC CancerVancouver, BC, CAvia HPV DNA testing and self-sampling
- Catalan Institute of Oncology (ICO)L'Hospitalet de Llobregat, ESvia HPV & HBV vaccination
- Centre Antoine LacassagneNice, FRvia IMRT / IGRT (modern external beam)
- via IMRT / IGRT (modern external beam)
- Comprehensive Cancer Center Freiburg (CCCF)Freiburg im Breisgau, DEvia IMRT / IGRT (modern external beam)
- Department of Biotechnology, Government of IndiaNew Delhi, INvia HPV & HBV vaccination
- European Cancer OrganisationBrussels, BEvia HPV & HBV vaccination
- via Brachytherapy
- Gates FoundationSeattle, WA, USvia HPV & HBV vaccination
- Geneva University Hospitals (HUG)Geneva, CHvia IMRT / IGRT (modern external beam)
- German Cancer Research Center (DKFZ)Heidelberg, DEvia HPV & HBV vaccination
- via IMRT / IGRT (modern external beam)
- via IMRT / IGRT (modern external beam)
- Hokkaido University HospitalSapporo, JPvia IMRT / IGRT (modern external beam)
- Hospital de Amor (Barretos Cancer Hospital)Barretos, BRvia HPV & HBV vaccination
- Hunan Cancer HospitalChangsha, CNvia IMRT / IGRT (modern external beam)
- Indiana University Melvin and Bren Simon Comprehensive Cancer CenterIndianapolis, IN, USNCI comprehensivevia Cisplatin
- Institut Jules BordetBrussels, BEvia Pembrolizumab
- Institut PasteurParis, FRvia HPV & HBV vaccination
- Instituto Nacional de Câncer (INCA)Rio de Janeiro, BRvia HPV & HBV vaccination
- via IMRT / IGRT (modern external beam)
- via Brachytherapy
- International Extranodal Lymphoma Study GroupBellinzona, CHvia IMRT / IGRT (modern external beam)
- IRCCS Humanitas Research HospitalRozzano (Milan), ITvia IMRT / IGRT (modern external beam)
- via IMRT / IGRT (modern external beam)
- Juravinski Cancer Centre / Escarpment Cancer Research InstituteHamilton, ON, CAvia IMRT / IGRT (modern external beam)
- Kaiser Permanente Division of ResearchOakland, CA, USvia HPV & HBV vaccination
- Koo Foundation Sun Yat-Sen Cancer CenterTaipei, TWvia Brachytherapy
- via Pembrolizumab
- via IMRT / IGRT (modern external beam)
- Leiden University Medical CenterLeiden, NLvia HPV & HBV vaccination
- via HPV & HBV vaccination
- via IMRT / IGRT (modern external beam)
- National Taiwan University HospitalTaipei, TWvia HPV & HBV vaccination
- NCI Center for Cancer Research (intramural programme)Bethesda, MD, USvia HPV & HBV vaccination
- via IMRT / IGRT (modern external beam)
- via IMRT / IGRT (modern external beam)
- Philippine General HospitalManila, PHvia HPV & HBV vaccination
- via Brachytherapy
- Rajiv Gandhi Cancer Institute and Research CentreNew Delhi, INvia IMRT / IGRT (modern external beam)
- Rambam Health Care CampusHaifa, ILvia IMRT / IGRT (modern external beam)
- Rigshospitalet – Copenhagen University HospitalCopenhagen, DKvia IMRT / IGRT (modern external beam)
- Royal Adelaide HospitalAdelaide, AUvia IMRT / IGRT (modern external beam)
- via IMRT / IGRT (modern external beam)
- Siriraj Hospital, Mahidol UniversityBangkok, THvia IMRT / IGRT (modern external beam)
- Sunnybrook Odette Cancer CentreToronto, ON, CAvia Brachytherapy
- Tata Medical Center, KolkataKolkata, INvia IMRT / IGRT (modern external beam)
- Tawam HospitalAl Ain, AEvia IMRT / IGRT (modern external beam)
- Tel Aviv Sourasky Medical CenterTel Aviv, ILvia IMRT / IGRT (modern external beam)
- via IMRT / IGRT (modern external beam)
- via HPV & HBV vaccination
- TROG Cancer ResearchNewcastle, NSW, AUvia IMRT / IGRT (modern external beam)
- UMC Utrecht Cancer CenterUtrecht, NLvia IMRT / IGRT (modern external beam)
- University of Malaya Medical CentreKuala Lumpur, MYvia IMRT / IGRT (modern external beam)
- via IMRT / IGRT (modern external beam)
- via IMRT / IGRT (modern external beam)
- via HPV & HBV vaccination
- Zhejiang Cancer HospitalHangzhou, CNvia IMRT / IGRT (modern external beam)
Questions to ask
topQuestions to ask your oncologist about Vaginal cancer
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 / p16 IHC, FIGO stage, PD-L1 CPS, Prior cervical neoplasia or hysterectomy history, DES exposure history), 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 Squamous cell carcinoma, Adenocarcinoma, Vaginal melanoma.
- Is germline (inherited) genetic testing recommended for me or my family?Why: Inherited variants can change treatment and matter for relatives.
VAIN 2 to 3
- For my situation (vain 2 to 3), which of the standard options do you recommend and why?Why: Guideline options include: Laser ablation, topical imiquimod or fluorouracil, or excision; surveillance after treatment of CIN 3 or hysterectomy for CIN.
Stage I, small upper-vaginal lesion
- For my situation (stage i, small upper-vaginal lesion), which of the standard options do you recommend and why?Why: Guideline options include: Wide excision or brachytherapy alone in selected cases.
Stage I to IVA, most patients
- For my situation (stage i to iva, most patients), which of the standard options do you recommend and why?Why: Guideline options include: External beam radiotherapy with concurrent weekly cisplatin followed by image-guided brachytherapy, extrapolated 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
- For my situation (recurrent or metastatic), which of the standard options do you recommend and why?Why: Guideline options include: Platinum-based chemotherapy; pembrolizumab for PD-L1-positive disease by extension from cervical cancer; salvage exenterative surgery for isolated central recurrence after radiotherapy.
- Am I a candidate for Cisplatin, 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, KEYNOTE-A18 / ENGOT-cx11 / GOG-3047, HPV & HBV vaccination?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 dedicated randomised trials; HPV-basket immunotherapy trials and international rare-tumour registries are filling the gap”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
- I read that “Optimal brachytherapy technique and dose for vaginal primaries; MRI-guided adaptive brachytherapy series are maturing”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
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Direct links plus the targets, companies, and technologies of this cancer's products.
technologies
9targets
2drugs
5companies
2pathways
1terms
4trials
2bottlenecks
2Latest papers
topQuery for this cancer: (TITLE:"Vaginal cancer" OR ABSTRACT:"Vaginal cancer" OR TITLE:"Vaginal squamous cell carcinoma" OR ABSTRACT:"Vaginal squamous cell carcinoma" OR TITLE:"Primary vaginal carcinoma" OR ABSTRACT:"Primary vaginal carcinoma" OR TITLE:"VAIN vaginal intraepithelial neoplasia; precursor" OR ABSTRACT:"VAIN vaginal intraepithelial neoplasia; precursor") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Vaginal cancer, not a curated reading list.
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