# Vaginal cancer

Source: https://onco.cc/cancers/vaginal/  
OnCo record `vaginal` (Cancer). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Primary vaginal cancer is rare and mostly caused by HPV, the virus behind cervical cancer. It is treated like cervical cancer, with weekly cisplatin alongside external and internal radiotherapy, which controls most tumours while preserving the organ; HPV vaccination and cervical screening, which also detects vaginal precursors, are steadily reducing it.

## Summary

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.

## Fields

- Kind: Cancer
- Last checked: 2026-09-10
- Also known as: Vaginal squamous cell carcinoma; Primary vaginal carcinoma; VAIN (vaginal intraepithelial neoplasia; precursor)
- Tags: nci-coverage; rare; gynaecologic; hpv
- Group: gynaecologic
- Burden: 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).
- Subtypes: 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)
- Biomarkers: 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)

## Sections of this record

The page is a hub with ten sections in reading order; large sections have their own page. The same plan as JSON: https://onco.cc/api/v1/cancers/vaginal/sections.json

- Overview (on the hub): The TL;DR, the family this cancer belongs to, the organ, who gets it and what the state of the art is. https://onco.cc/cancers/vaginal/#overview [3 subtypes, 4 state-of-the-art points]
- What it is (on the hub): Anatomy, the subtypes and how they differ, how it is staged, and where advanced disease spreads. https://onco.cc/cancers/vaginal/#what-it-is [8 subtypes]
- Finding it (on the hub): How it shows itself, how it is confirmed, what screening exists, and the biomarkers clinicians test for. https://onco.cc/cancers/vaginal/#finding-it [5 biomarkers]
- Treating it (on the hub): The standard of care by setting, the medicines, surgery and radiotherapy named in it, and the regimens behind them. https://onco.cc/cancers/vaginal/#treating-it [4 settings, 3 decisions with options]
- Evidence (on the hub): Trials recruiting now, the landmark trials, the key papers and what they mean, the latest literature, and the milestones year by year. https://onco.cc/cancers/vaginal/#evidence [6 trials, 1 key paper, 5 milestones]
- The science (on the hub): The molecular landscape: the targets and how often each appears, the pathways, the mechanics stages and the preclinical models. https://onco.cc/cancers/vaginal/#science [2 targets, 1 pathway]
- Where you are (own page): Cases by country, the UK and NHS pathway and other country lenses, and the expert centres with trials on record. https://onco.cc/cancers/vaginal/where-you-are/
- Living with it (on the hub): The decisions you may face, the aids that walk through them, the warnings on record, the first sixty days and the questions to ask. https://onco.cc/cancers/vaginal/#living-with-it [16 questions, 6 red cards]
- What is coming (own page): Everything in development, the open problems and what is being done about them, the roadmaps, and what changed on this record. https://onco.cc/cancers/vaginal/coming/ [5 medicines, 4 trials, 4 open problems]
- Data (own page): Every connected record, the notes, the JSON, Markdown and RDF twins, and where the record came from and when it was checked. https://onco.cc/cancers/vaginal/data/ [38 connected records]

## Standard of care

- VAIN 2 to 3: Laser ablation, topical imiquimod or fluorouracil, or excision; surveillance after treatment of CIN 3 or hysterectomy for CIN. ([HPV DNA testing and self-sampling](https://onco.cc/technologies/hpv-testing/), [Colposcopy and excisional treatment (LEEP/LLETZ, cone)](https://onco.cc/technologies/colposcopy-excision/), [Thermal ablation and cryotherapy for cervical precancer](https://onco.cc/technologies/precancer-ablation/))
- Stage I, small upper-vaginal lesion: Wide excision or brachytherapy alone in selected cases. ([Brachytherapy](https://onco.cc/technologies/brachytherapy/))
- Stage I to IVA, most patients: External beam radiotherapy with concurrent weekly cisplatin followed by image-guided brachytherapy, extrapolated from cervical cancer. ([Cisplatin](https://onco.cc/drugs/cisplatin/), [IMRT / IGRT (modern external beam)](https://onco.cc/technologies/imrt-igrt/), [Brachytherapy](https://onco.cc/technologies/brachytherapy/), [Chemoradiation (chemoradiotherapy, CRT)](https://onco.cc/terms/chemoradiation/))
- Recurrent or metastatic: Platinum-based chemotherapy; pembrolizumab for PD-L1-positive disease by extension from cervical cancer; salvage exenterative surgery for isolated central recurrence after radiotherapy. ([Cisplatin](https://onco.cc/drugs/cisplatin/), [Paclitaxel / nab-paclitaxel](https://onco.cc/drugs/paclitaxel/), [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/), [KEYNOTE-826](https://onco.cc/trials/keynote-826/))

## State of the art

- 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.
- Survivorship issues (vaginal stenosis, sexual function, bladder and bowel toxicity) are addressed with dilator programmes and MRI-guided adaptive brachytherapy.

## Open problems

- No dedicated randomised trials; HPV-basket immunotherapy trials and international rare-tumour registries are filling the gap.
- 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.
- Surveillance of women treated for CIN 3 to catch VAIN early.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Vaginal_cancer
- NCI PDQ: vaginal cancer: https://www.cancer.gov/types/vaginal
- ESGO / ESTRO / ESP rare gynaecological cancers (vaginal cancer) guidance: https://doi.org/10.1016/j.radonc.2023.109590
- NCCN: Vulvar Cancer (includes vaginal cancer principles): https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1476
- SEER: vaginal cancer: https://seer.cancer.gov/statfacts/html/vagina.html

## Connected records

- cancers: [Anal cancer (squamous cell carcinoma)](https://onco.cc/cancers/anal/), [Cervical cancer](https://onco.cc/cancers/cervical/), [Rhabdomyosarcoma](https://onco.cc/cancers/rhabdomyosarcoma/), [Vaginal adenocarcinoma (including DES-associated clear cell adenocarcinoma)](https://onco.cc/cancers/vaginal-adenocarcinoma/), [Vaginal melanoma](https://onco.cc/cancers/vaginal-melanoma/), [Vaginal squamous cell carcinoma (HPV-associated)](https://onco.cc/cancers/vaginal-squamous-cell-carcinoma/), [Vulvar cancer](https://onco.cc/cancers/vulvar/)
- technologies: [Brachytherapy](https://onco.cc/technologies/brachytherapy/), [Colposcopy and excisional treatment (LEEP/LLETZ, cone)](https://onco.cc/technologies/colposcopy-excision/), [Cytotoxic chemotherapy](https://onco.cc/technologies/cytotoxic-chemotherapy/), [HPV & HBV vaccination](https://onco.cc/technologies/hpv-vaccine/), [HPV DNA testing and self-sampling](https://onco.cc/technologies/hpv-testing/), [Immune checkpoint inhibitors](https://onco.cc/technologies/checkpoint-inhibitor/), [IMRT / IGRT (modern external beam)](https://onco.cc/technologies/imrt-igrt/), [Thermal ablation and cryotherapy for cervical precancer](https://onco.cc/technologies/precancer-ablation/)
- targets: [PD-1](https://onco.cc/targets/pd1/), [PD-L1](https://onco.cc/targets/pdl1/)
- drugs: [Cisplatin](https://onco.cc/drugs/cisplatin/), [Fluorouracil (5-FU)](https://onco.cc/drugs/fluorouracil/), [Nonavalent HPV vaccine](https://onco.cc/drugs/gardasil-9/), [Paclitaxel / nab-paclitaxel](https://onco.cc/drugs/paclitaxel/), [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/)
- pathways: [Oncogenic viruses](https://onco.cc/pathways/oncogenic-viruses/)
- terms: [Cervical precancer (CIN, HSIL/LSIL)](https://onco.cc/terms/cin-hsil/), [Chemoradiation (chemoradiotherapy, CRT)](https://onco.cc/terms/chemoradiation/), [HPV status (HPV-positive / HPV-negative)](https://onco.cc/terms/hpv-status/), [HPV-positive (p16) head and neck cancer](https://onco.cc/terms/hpv-p16/)
- trials: [Artesunate Vaginal Inserts for the Treatment of Cervical Intraepithelial Neoplasia (CIN2/3)](https://onco.cc/trials/nct04098744/), [Evaluate the Efficacy, Immunogenicity and Safety of 9-valent HPV Recombinant Vaccine in Chinese Healthy Females](https://onco.cc/trials/nct04422366/), [Immunogenicity and Safety of Quadrivalent HPV Vaccine in Healthy Chinese Female Subjects Aged 9 to 19 Years](https://onco.cc/trials/nct05027776/), [KEYNOTE-826](https://onco.cc/trials/keynote-826/), [KEYNOTE-A18 / ENGOT-cx11 / GOG-3047](https://onco.cc/trials/keynote-a18/), [Phase II Study of Dysplasix™ Intravaginal Suppositories in Patients Patients With High-Risk HPV and Mild Cervical Cytologic Abnormalities](https://onco.cc/trials/nct07572396/)
- bottlenecks: [Prevention we already have is not deployed](https://onco.cc/bottlenecks/b-prevention-adoption/), [Rare and paediatric cancers without markets](https://onco.cc/bottlenecks/b-rare-cancers/)
- key papers: [Seed-displacements in the immediate post-implant phase in permanent prostate brachytherapy](https://onco.cc/key-papers/paper-karius-radiother-oncol/)
- journals: [International journal of gynecological cancer](https://onco.cc/journals/international-journal-of-gynecological-cancer/), [Journal of gynecologic oncology](https://onco.cc/journals/journal-of-gynecologic-oncology/)
- companies: [Frantz Viral Therapeutics](https://onco.cc/companies/frantz-viral-therapeutics/), [Shanghai Bovax Biotechnology](https://onco.cc/companies/shanghai-bovax-biotechnology/)

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JSON: https://onco.cc/api/v1/entities/vaginal.json