DESCRIPTION

• Primary carcinomas of the vagina are rare: 2–3% of gynecologic malignancies and 1,372 new cases annually in the United States as of 2021 (1)
• Vaginal intraepithelial neoplasia (VAIN), the precursor lesion for vaginal cancer, is defined by squamous cell atypia and is classified by the depth of epithelial involvement (2)
  • 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 vaginal cancer can spread by direct extension to adjacent tissues, lymphatic dissemination to locoregional lymph nodes (pelvic and para-aortic, or inguinal), or via hematogenous squamous cell carcinoma; has the potential for hematogenous metastasis to other sites including the lungs and liver.
• To be classified as a primary 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 cannot be classified as a primary vaginal malignancy.
• If the patient has a cervix, then a primary cervical malignancy should be conclusively ruled out before vaginal cancer diagnosis can be made.
• Most vaginal malignancies are metastatic tumors from other primary sites (e.g., cervix, vulva, endometrium).

Pregnancy Considerations
This malignancy is not typically associated with pregnancy (3).

EPIDEMIOLOGY

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.
• There is a higher risk of vaginal cancer in patients who smoke cigarettes.
• Clear cell adenocarcinoma of the vagina in young women has been associated with DES exposure in utero. 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

RISK FACTORS

• Similar risk factors as cervical cancer, including smoking, HPV exposure, immunodeficiency
• Age
• African American
• Multiple sex partners, early age of first sexual intercourse
• History of squamous cell cancer of the cervix or vulva
• Vaginal adenosis, often associated with DES exposure
• Vaginal irritation
• DES exposure in utero
• Prior pelvic radiation

COMMONLY ASSOCIATED CONDITIONS

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