# Vaginal adenocarcinoma (including DES-associated clear cell adenocarcinoma)

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

## TL;DR

Vaginal adenocarcinoma is a rare glandular form of vaginal cancer, best known through the clear cell type that struck young women whose mothers took the hormone DES in pregnancy. Unlike the common squamous form it is not caused by HPV, it is treated with surgery where possible because it often affects young women, and radiotherapy and platinum chemotherapy are used when it is advanced.

## Summary

Adenocarcinoma of the vagina is uncommon and heterogeneous. The clear cell type arises from adenosis, glandular tissue left in the vagina when the Müllerian epithelium fails to be replaced, and in 1971 Arthur Herbst linked a cluster of cases in teenagers and young women in Boston to their mothers' use of diethylstilboestrol (DES) in early pregnancy, the first proof that a drug taken in pregnancy could cause cancer in the child decades later. DES was withdrawn for that use the same year; exposed women carry a lifetime risk of about one in a thousand, most tumours appeared between the ages of 15 and 30, and cases still occur as the cohort ages. Sporadic clear cell, endometrioid, mucinous and mesonephric adenocarcinomas also arise, usually in older women, and any vaginal adenocarcinoma must first be shown not to be a metastasis from the endometrium, cervix, ovary or bowel.

Treatment follows the same stage-based principles as squamous cell carcinoma, but with a greater place for surgery because patients with DES-associated disease were young and fertility and vaginal function mattered: radical vaginectomy or hysterectomy with lymphadenectomy for early upper-vaginal tumours, sometimes with vaginal reconstruction, and radiotherapy with brachytherapy for larger or lower tumours or after surgery. Clear cell tumours spread to lymph nodes early and can recur late, so follow-up is prolonged. Advanced or recurrent disease is treated with platinum-based chemotherapy, extrapolating from clear cell cancers of the ovary and cervix, and immunotherapy is being explored because clear cell carcinomas at other sites respond in a minority. The DES story remains the model for transplacental carcinogenesis and led to lifelong surveillance programmes for exposed daughters.

## Fields

- Kind: Cancer
- Last checked: 2026-09-18
- Also known as: Clear cell adenocarcinoma of the vagina; DES-associated vaginal cancer; Vaginal adenocarcinoma; Mesonephric and endometrioid adenocarcinoma of the vagina
- Tags: subtype-page; gynaecologic
- Group: gynaecologic
- Burden: A small minority of vaginal cancers; the clear cell form appeared as an epidemic in young women exposed to diethylstilboestrol before birth between the 1940s and 1971 and is now rare, while adenocarcinomas in older women are usually metastases rather than primaries.
- Subtypes: DES-associated clear cell adenocarcinoma of the vagina (young women, adenosis); Sporadic clear cell adenocarcinoma of the vagina; Endometrioid and mucinous vaginal adenocarcinoma; Mesonephric adenocarcinoma of the vagina; Vaginal metastasis from endometrial, cervical, ovarian or bowel adenocarcinoma (to be excluded)
- Biomarkers: Prenatal DES exposure history; Vaginal adenosis on examination and biopsy; Immunohistochemistry to separate primary from metastatic adenocarcinoma (PAX8, ER, CDX2, napsin A, HNF1 beta); HPV and p16 status (usually negative); FIGO stage (MRI, PET-CT); Mismatch repair and PD-L1 status (immunotherapy candidacy)

## Standard of care

- Diagnosis: Biopsy with immunohistochemistry to exclude metastasis; MRI and PET-CT staging; DES exposure history. ([Histopathology & immunohistochemistry](https://onco.cc/technologies/histopathology-ihc/), [MRI](https://onco.cc/technologies/mri/), [PET/CT](https://onco.cc/technologies/pet-ct/))
- Early stage: Radical vaginectomy or radical hysterectomy with lymphadenectomy, with vaginal reconstruction and ovarian preservation where appropriate; adjuvant radiotherapy for close margins or positive nodes. ([Lymphadenectomy (lymph node dissection)](https://onco.cc/terms/lymphadenectomy/), [Oncofertility and fertility preservation](https://onco.cc/technologies/fertility-preservation/), [IMRT / IGRT (modern external beam)](https://onco.cc/technologies/imrt-igrt/))
- Locally advanced disease: External beam radiotherapy with brachytherapy, with concurrent cisplatin by extrapolation 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: Platinum-based chemotherapy (carboplatin and paclitaxel); checkpoint inhibitors for mismatch-repair-deficient or PD-L1-positive tumours; pelvic exenteration for isolated central recurrence. ([Carboplatin](https://onco.cc/drugs/carboplatin/), [Paclitaxel / nab-paclitaxel](https://onco.cc/drugs/paclitaxel/), [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/))
- DES-exposed women: Lifelong annual gynaecological examination with cytology of the cervix and vagina and colposcopy of adenosis. ([Colposcopy and excisional treatment (LEEP/LLETZ, cone)](https://onco.cc/technologies/colposcopy-excision/))

## State of the art

- The DES cohort established that prenatal drug exposure can cause cancer decades later and remains under surveillance.
- Surgery with reconstruction gives good outcomes in early disease in young women.
- Systemic therapy is borrowed from clear cell cancers of other organs.

## Open problems

- No trial-based treatment exists; everything is extrapolated from cervical and ovarian cancer.
- The natural history of late recurrence in clear cell tumours means decades of follow-up.
- DES-exposed women are now in their fifties to seventies and the shape of their late risk is uncertain.
- Sporadic adenocarcinomas are so rare that their biology is barely studied.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Vaginal_cancer
- Herbst 1971 (NEJM): https://doi.org/10.1056/NEJM197104222841604
- Wikipedia: https://en.wikipedia.org/wiki/Vaginal_cancer

## Connected records

- cancers: [Clear cell ovarian cancer](https://onco.cc/cancers/clear-cell-ovarian-cancer/), [Vaginal cancer](https://onco.cc/cancers/vaginal/), [Vaginal squamous cell carcinoma (HPV-associated)](https://onco.cc/cancers/vaginal-squamous-cell-carcinoma/)
- technologies: [Brachytherapy](https://onco.cc/technologies/brachytherapy/), [Colposcopy and excisional treatment (LEEP/LLETZ, cone)](https://onco.cc/technologies/colposcopy-excision/), [Histopathology & immunohistochemistry](https://onco.cc/technologies/histopathology-ihc/), [IMRT / IGRT (modern external beam)](https://onco.cc/technologies/imrt-igrt/), [MRI](https://onco.cc/technologies/mri/), [Oncofertility and fertility preservation](https://onco.cc/technologies/fertility-preservation/), [PET/CT](https://onco.cc/technologies/pet-ct/)
- drugs: [Carboplatin](https://onco.cc/drugs/carboplatin/), [Cisplatin](https://onco.cc/drugs/cisplatin/), [Paclitaxel / nab-paclitaxel](https://onco.cc/drugs/paclitaxel/), [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/)
- terms: [Chemoradiation (chemoradiotherapy, CRT)](https://onco.cc/terms/chemoradiation/), [HPV status (HPV-positive / HPV-negative)](https://onco.cc/terms/hpv-status/), [Lymphadenectomy (lymph node dissection)](https://onco.cc/terms/lymphadenectomy/)
- key papers: [Adenocarcinoma of the vagina: association of maternal stilbestrol therapy with tumour appearance in young women](https://onco.cc/key-papers/paper-herbst-diethylstilbestrol-vaginal-adenocarcinoma-nejm-1971/), [FIGO Cancer Report 2018: cancer of the vagina](https://onco.cc/key-papers/paper-figo-cancer-report-cancer-of-the-vagina-ijgo-2018/)

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