Vaginal adenocarcinoma (including DES-associated clear cell adenocarcinoma)
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.
Overview
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 DES was withdrawn for that use the same year; exposed women carry a lifetime risk of about one in a thousand, most tumours appeared between the ages of 15 and 30, and cases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.
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.
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 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: 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).
- Check before combiningKidneys: Cisplatin
Dose reduce or avoid for CrCl below 60 (carboplatin is the alternative).
- Good to knowImmune-related endocrinopathies (thyroiditis, hypophysitis)
Immunotherapy can attack hormone-producing glands: most often the thyroid (usually ending in an under-active thyroid needing lifelong tablets), and less often the pituitary (hypophysitis) or adrenal glands, which can be life-threatening if missed.
See all on the product pages:CarboplatinCisplatinPaclitaxel / 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)DES-associated clear cell adenocarcinoma of the vagina (young women, adenosis) · Sporadic clear cell adenocarcinoma of the vagina · Endometrioid and mucinous vaginal adenocarcinoma
- EndometriumEndometrioid and mucinous vaginal adenocarcinoma
- Myometrium (uterine sarcoma)
- Placental site (gestational trophoblastic)
- Cervix, transformation zoneDES-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)
- Vulva
- 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 squamous cell carcinoma (HPV-associated), 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
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.
- MRIStandard 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.
Biopsy with immunohistochemistry to exclude metastasis; MRI and PET-CT staging; DES exposure history.
Radical vaginectomy or radical hysterectomy with lymphadenectomy, with vaginal reconstruction and ovarian preservation where appropriate; adjuvant radiotherapy for close margins or positive nodes.
External beam radiotherapy with brachytherapy, with concurrent cisplatin by extrapolation from cervical cancer.
Platinum-based chemotherapy (carboplatin and paclitaxel); checkpoint inhibitors for mismatch-repair-deficient or PD-L1-positive tumours; pelvic exenteration for isolated central recurrence.
Lifelong annual gynaecological examination with cytology of the cervix and vagina and colposcopy of adenosis.
Subtypes & biomarkers
top- 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)
- 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)
How often this target appears
- 1971Herbst links vaginal clear cell adenocarcinoma in young women to prenatal DES exposure; the FDA advises against DES in pregnancy
- 1992Registry data define the lifetime risk in DES-exposed daughters at about one in a thousand
- 2011Long-term follow-up of the DES cohort confirms continued excess of clear cell adenocarcinoma and other harms
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 4 changes by month →- 2026-09-18This recordVaginal adenocarcinoma (including DES-associated clear cell adenocarcinoma)Facts on this page last checked
When this page itself was last checked or edited.
- 2011MilestoneVaginal adenocarcinoma (including DES-associated clear cell adenocarcinoma)Long-term follow-up of the DES cohort confirms continued excess of clear cell adenocarcinoma and other harms
A milestone in how this cancer is treated.
- 1992MilestoneVaginal adenocarcinoma (including DES-associated clear cell adenocarcinoma)Registry data define the lifetime risk in DES-exposed daughters at about one in a thousand
A milestone in how this cancer is treated.
- 1971MilestoneVaginal adenocarcinoma (including DES-associated clear cell adenocarcinoma)Herbst links vaginal clear cell adenocarcinoma in young women to prenatal DES exposure; the FDA advises against DES in pregnancy
A milestone in how this cancer is treated.
What is in development for Vaginal adenocarcinoma (including DES-associated clear cell adenocarcinoma), drawn from the whole corpus: 0 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.
Nothing recorded in development for this cancer yet.
Open problems and what is being done
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.
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.
Expert centres
topExpert centres
Baltimore · cancer center | United States | 0 | 2,955 | 41,449 | #10 | ||
Utrecht · cancer center | Netherlands | none recorded | 0 | 1,422 | 20,323 | - | |
Tianjin · cancer center | China | none recorded | 0 | 1,219 | 11,455 | - | |
Hangzhou · cancer center | China | none recorded | 0 | 1,219 | 17,635 | - | |
Beijing · hospital | China | none recorded | 0 | 1,154 | 11,808 | - | |
Rozzano (Milan) · hospital | Italy | none recorded | 0 | 1,031 | 10,720 | - | |
Changsha · cancer center | China | none recorded | 0 | 930 | 14,477 | - | |
Jinan · cancer center | China | none recorded | 0 | 920 | 7,804 | - | |
Rotterdam · cancer center | Netherlands | none recorded | 0 | 852 | 12,180 | - | |
Dresden · cancer center | Germany | none recorded | 0 | 728 | 7,984 | - | |
| United Kingdom | none recorded | 0 | 693 | 7,168 | - | ||
Chennai · cancer center | India | none recorded | 0 | 691 | 13,919 | - | |
Aarhus · hospital | Denmark | none recorded | 0 | 624 | 4,497 | - | |
Freiburg im Breisgau · cancer center | Germany | none recorded | 0 | 549 | 5,261 | - | |
Basel · hospital | Switzerland | none recorded | 0 | 544 | 6,056 | - |
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 adenocarcinoma 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 adenocarcinoma
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 Prenatal DES exposure history, Vaginal adenosis on examination and biopsy, Immunohistochemistry to separate primary from metastatic adenocarcinoma, HPV and p16 status, FIGO stage), 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 DES-associated clear cell adenocarcinoma of the vagina, Sporadic clear cell adenocarcinoma of the vagina, Endometrioid and mucinous vaginal adenocarcinoma.
- Is germline (inherited) genetic testing recommended for me or my family?Why: Inherited variants can change treatment and matter for relatives.
Diagnosis
- For my situation (diagnosis), which of the standard options do you recommend and why?Why: Guideline options include: Biopsy with immunohistochemistry to exclude metastasis; MRI and PET-CT staging; DES exposure history.
Early stage
- For my situation (early stage), which of the standard options do you recommend and why?Why: Guideline options include: Radical vaginectomy or radical hysterectomy with lymphadenectomy, with vaginal reconstruction and ovarian preservation where appropriate; adjuvant radiotherapy for close margins or positive nodes.
Locally advanced disease
- For my situation (locally advanced disease), which of the standard options do you recommend and why?Why: Guideline options include: External beam radiotherapy with brachytherapy, with concurrent cisplatin by extrapolation 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: Platinum-based chemotherapy (carboplatin and paclitaxel); checkpoint inhibitors for mismatch-repair-deficient or PD-L1-positive tumours; pelvic exenteration for isolated central recurrence.
- 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.
DES-exposed women
- For my situation (des-exposed women), which of the standard options do you recommend and why?Why: Guideline options include: Lifelong annual gynaecological examination with cytology of the cervix and vagina and colposcopy of adenosis.
Any stage
- Are there clinical trials I could join, for example of Pembrolizumab?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 trial-based treatment exists; everything is extrapolated from cervical and ovarian cancer”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
- I read that “The natural history of late recurrence in clear cell tumours means decades of follow-up”. 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 adenocarcinoma, 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
10targets
1drugs
4companies
3terms
3key papers
2The treatment pathway on the vaginal cancer pages, radiotherapy with brachytherapy and cisplatin sensitisation for locally advanced disease, follows this report.
Clear cell adenocarcinoma of the vagina is the archetype of a cancer caused by exposure before birth; DES-exposed daughters still need lifelong gynaecological surveillance, and the paper is the reason drugs in pregnancy are now scrutinised for effects on the child.
Latest papers
topQuery for this cancer: (TITLE:"Vaginal adenocarcinoma" OR ABSTRACT:"Vaginal adenocarcinoma" OR TITLE:"including DES-associated clear cell adenocarcinoma" OR ABSTRACT:"including DES-associated clear cell adenocarcinoma" OR TITLE:"Clear cell adenocarcinoma of the vagina" OR ABSTRACT:"Clear cell adenocarcinoma of the vagina" OR TITLE:"DES-associated vaginal cancer" OR ABSTRACT:"DES-associated vaginal cancer" OR TITLE:"Mesonephric and endometrioid adenocarcinoma of the vagina" OR ABSTRACT:"Mesonephric and endometrioid adenocarcinoma of the vagina") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Vaginal adenocarcinoma (including DES-associated clear cell adenocarcinoma), not a curated reading list.
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