Vaginal Malignancy



  • Carcinomas of the vagina are uncommon: 2–3% of gynecologic malignancies; 2,300 new cases annually.
  • Vaginal intraepithelial neoplasia (VAIN), defined by squamous cell atypia, is classified by the depth of epithelial involvement:
    • VAIN 1: 1/3 thickness
    • VAIN 2: 2/3 thickness
    • VAIN 3: >2/3 thickness
    • Carcinoma in situ (CIS): designating full-thickness neoplastic changes without invasion through the basement membrane
  • Invasive malignancies: Vaginal malignancies include squamous cell carcinoma (85–90%), adenocarcinoma (5–10%), sarcoma (2–3%), and melanoma (2–3%). Clear cell carcinoma is a subtype of adenocarcinoma. Invasive squamous cell carcinoma has the potential for metastasis to the lungs and liver.
  • To be classified as a vaginal malignancy, only the vagina can be involved. If the cervix or vulva is involved, then the tumor is classified as a primary cancer arising from the cervix or the vulva. Additionally, if the patient has had a diagnosis of invasive cervical or vulvar cancer in the preceding 5 years, it can not be classified as a primary vaginal malignancy.
  • Most vaginal malignancies are metastatic tumors from other primary sites (e.g., cervix, vulva, endometrium, breast, ovary).
  • Most common sites of primary vaginal cancer metastases: lung, liver, bone

Pregnancy Considerations
This malignancy is not typically associated with pregnancy.


Predominant age

  • CIS: mid-40 to 60 years
  • Invasive squamous cell malignancy: mid-60 to 70 years
  • Adenocarcinoma: any age; 50 years is the mean age. Peak incidence is between 17 and 21 years of age.
  • Clear cell adenocarcinoma occurs most often in females aged <30 years with a history of exposure to diethylstilbestrol (DES) in utero.
  • Mixed müllerian sarcomas and leiomyosarcomas in the adult population: mean age is 60 years

Pediatric Considerations
Vaginal tumors are extremely rare. Rhabdomyosarcoma (botryoid and embryonal subtype) is the most common malignant neoplasm of the vagina. Less common entities are germ cell tumor and clear cell adenocarcinoma.

In the United States, it is one of the rarest of all gynecologic malignancies (3%).

Etiology and Pathophysiology

  • Women with a history of cervical malignancy have a higher probability of developing squamous cell malignancy in the vagina, even after hysterectomy.
  • Human papillomavirus (HPV) is found in 80–93% of patients with vaginal CIS and 50–65% of the patients with invasive vaginal carcinoma.
  • HPV-16 is the most common, found in 66% of CIS and 55% of invasive vaginal cancers.
  • Smokers have a higher incidence.
  • Clear cell adenocarcinoma of the vagina in young women has been associated with DES exposure. The incidence, however, is exceedingly rare, estimated at 1/1,000 to 1/10,000 exposed females.
  • Metastatic lesions can involve the vagina, spreading from the other gynecologic organs.
  • Although rare, renal cell carcinoma, lung adenocarcinoma, GI cancer, pancreatic adenocarcinoma, ovarian germ cell cancer, trophoblastic neoplasm, and breast cancer can all metastasize to the vagina.

No known genetic pattern

Risk Factors

  • Similar risk factors as cervical cancer
  • Age
  • African American
  • Smoking
  • Multiple sex partners, early age of first sexual intercourse
  • History of squamous cell cancer of the cervix or vulva
  • HPV infection
  • Vaginal adenosis
  • Vaginal irritation
  • DES exposure in utero
  • Immunocompromised, HIV
  • Prior pelvic radiation

Commonly Associated Conditions

Due to the field effect, patients with vaginal cancer are more likely to develop malignancy in the cervix or vulva and should be followed closely.

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