# Vaginal squamous cell carcinoma (HPV-associated)

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

## TL;DR

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.

## Summary

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.

## Fields

- Kind: Cancer
- Last checked: 2026-09-18
- Also known as: Primary vaginal squamous cell carcinoma; HPV-related vaginal cancer; Vaginal cancer treated with chemoradiotherapy; VAIN and vaginal squamous carcinoma
- Tags: subtype-page; gynaecologic
- Group: gynaecologic
- Burden: 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.
- Subtypes: 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)
- Biomarkers: 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)

## 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-squamous-cell-carcinoma/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-squamous-cell-carcinoma/#overview [3 state-of-the-art points]
- Types and stages (on the hub): Anatomy, the subtypes and how they differ, how it is staged, and where advanced disease spreads. https://onco.cc/cancers/vaginal-squamous-cell-carcinoma/#what-it-is [5 subtypes]
- Symptoms and diagnosis (on the hub): How this cancer shows itself, how the diagnosis is confirmed, and the biomarkers clinicians test for. https://onco.cc/cancers/vaginal-squamous-cell-carcinoma/#finding-it [5 biomarkers]
- Treatment (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-squamous-cell-carcinoma/#treating-it [4 settings, 3 decisions with options]
- Trials and papers (on the hub): Trials recruiting now, the landmark trials, the trials held by this cancer's subtypes, the key papers and what they mean, the latest literature, and the milestones year by year. https://onco.cc/cancers/vaginal-squamous-cell-carcinoma/#evidence [4 trials, 2 key papers, 4 milestones]
- Biology and targets (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-squamous-cell-carcinoma/#science [2 targets]
- Countries and centres (own page): Cases by country, the UK and NHS pathway and other country lenses, the expert centres with trials on record, and the centres named on this cancer's subtypes. https://onco.cc/cancers/vaginal-squamous-cell-carcinoma/where-you-are/
- Decisions and support (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-squamous-cell-carcinoma/#living-with-it [18 questions, 6 red cards]
- Pipeline and open problems (own page): Everything in development, the medicines held by this cancer's subtypes, the open problems and what is being done about them, the roadmaps, and what changed on this record. https://onco.cc/cancers/vaginal-squamous-cell-carcinoma/coming/ [6 medicines, 1 trial, 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-squamous-cell-carcinoma/data/ [32 connected records]

## Standard of care

- Precursor (VAIN): Laser ablation or excision; topical imiquimod or fluorouracil; brachytherapy for extensive vault disease; HPV vaccination and screening for prevention. ([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/), [Fluorouracil (5-FU)](https://onco.cc/drugs/fluorouracil/), [Brachytherapy](https://onco.cc/technologies/brachytherapy/), [HPV & HBV vaccination](https://onco.cc/technologies/hpv-vaccine/), [Nonavalent HPV vaccine](https://onco.cc/drugs/gardasil-9/), [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/))
- Stage I, upper vagina: Radical upper vaginectomy with pelvic lymphadenectomy, or brachytherapy with or without external beam radiotherapy. ([Brachytherapy](https://onco.cc/technologies/brachytherapy/), [Lymphadenectomy (lymph node dissection)](https://onco.cc/terms/lymphadenectomy/))
- Stage II to IVA: External beam radiotherapy to the pelvis (and groins for lower-third tumours) with concurrent weekly cisplatin, followed by brachytherapy, extrapolating from cervical cancer. ([IMRT / IGRT (modern external beam)](https://onco.cc/technologies/imrt-igrt/), [Brachytherapy](https://onco.cc/technologies/brachytherapy/), [Cisplatin](https://onco.cc/drugs/cisplatin/), [Chemoradiation (chemoradiotherapy, CRT)](https://onco.cc/terms/chemoradiation/))
- Recurrent or metastatic disease: Carboplatin and paclitaxel with or without bevacizumab; pembrolizumab for PD-L1-positive tumours (KEYNOTE-826 extrapolated); pelvic exenteration for isolated central recurrence after radiotherapy. ([Carboplatin](https://onco.cc/drugs/carboplatin/), [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

- 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.

## Open problems

- No randomised trial has ever been conducted in vaginal cancer.
- Radiotherapy causes vaginal stenosis and sexual morbidity that are poorly addressed.
- The role of chemotherapy with radiotherapy is assumed, not proven.
- Tumours at the vault after hysterectomy are hard to distinguish from recurrent cervical cancer.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Vaginal_cancer
- NCCN Vaginal Cancer: https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1481
- Wikipedia: https://en.wikipedia.org/wiki/Vaginal_cancer

## Connected records

- cancers: [HPV-associated vulvar squamous cell carcinoma](https://onco.cc/cancers/hpv-associated-vulvar-cancer/), [Locally advanced cervical cancer](https://onco.cc/cancers/locally-advanced-cervical-cancer/), [Vaginal adenocarcinoma (including DES-associated clear cell adenocarcinoma)](https://onco.cc/cancers/vaginal-adenocarcinoma/), [Vaginal cancer](https://onco.cc/cancers/vaginal/), [Vaginal melanoma](https://onco.cc/cancers/vaginal-melanoma/)
- technologies: [Brachytherapy](https://onco.cc/technologies/brachytherapy/), [Colposcopy and excisional treatment (LEEP/LLETZ, cone)](https://onco.cc/technologies/colposcopy-excision/), [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: [Carboplatin](https://onco.cc/drugs/carboplatin/), [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/)
- 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/), [Lymphadenectomy (lymph node dissection)](https://onco.cc/terms/lymphadenectomy/)
- trials: [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/), [Phase II Study of Dysplasix™ Intravaginal Suppositories in Patients Patients With High-Risk HPV and Mild Cervical Cytologic Abnormalities](https://onco.cc/trials/nct07572396/)
- key papers: [Carcinoma of the vagina: FIGO 26th Annual Report on the results of treatment in gynecological cancer](https://onco.cc/key-papers/paper-figo-annual-report-carcinoma-of-the-vagina-ijgo-2006/), [FIGO Cancer Report 2018: cancer of the vagina](https://onco.cc/key-papers/paper-figo-cancer-report-cancer-of-the-vagina-ijgo-2018/)

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JSON: https://onco.cc/api/v1/entities/vaginal-squamous-cell-carcinoma.json