Vaginal intraepithelial neoplasia (VaIN) and vaginal cancer

Definition

• Vaginal intraepithelial neoplasia (VaIN) is a rare precancerous lesion of the vaginal epithelium that is strongly associated with HPV and can progress to vaginal cancer.
• By definition, primary vaginal cancer requires the absence of current cervical or vulvar cancer and of a history of either within the past 5 years.

Classification

• In the 2020 WHO classification, VaIN 1 corresponds to a low-grade (LSIL) and VaIN 2 and 3 to a high-grade squamous intraepithelial lesion (HSIL).
• Studies report a risk of 2–12 % for progression of HSIL to vaginal cancer.
• The great majority of primary vaginal cancers are squamous cell carcinomas; adenocarcinoma, clear cell carcinoma and melanoma are rarer, and the most common vaginal sarcoma is sarcoma botryoides.

Occurrence & epidemiology

Epidemiology

• VaIN is rare; its incidence is about 100 times lower than that of cervical intraepithelial neoplasia.
• Primary vaginal cancer is rare, accounting for 1–2 % of gynaecological cancers; metastases or local extension from adjacent tumours are more common in the vagina than primary tumours.
• Vaginal cancer most often occurs in women over 60; the average age at diagnosis is 60–65 years.

Aetiopathogenesis

Aetiology and risk factors

• Most vaginal cancers are caused by persistent HPV infection; more than 80 % of high-grade VaIN cases are attributable to oncogenic HPV types, mainly HPV 16 and 18.
• Risk factors for vaginal cancer include HPV, VaIN and cervical, vulvar or anal intraepithelial neoplasia or cancer; smoking, immunodeficiency and chlamydial infection are also cited for VaIN.
• In utero exposure to diethylstilbestrol predisposes to the rare clear cell adenocarcinoma of the vagina, which is diagnosed at a mean age of 19 years.

Clinical features

• VaIN usually causes no noticeable symptoms and is often diagnosed incidentally on the basis of abnormal cytology or histology.
• The most common presenting symptom of vaginal cancer is abnormal vaginal bleeding, often postmenopausal or postcoital; some women have watery discharge or dyspareunia, and few are asymptomatic.
• Most vaginal cancers occur in the upper third of the posterior vaginal wall; vesicovaginal or rectovaginal fistulas are manifestations of advanced disease.

Diagnosis

• Cytology alone has limited ability to detect VaIN; evaluation includes colposcopy with iodine (Lugol) staining and targeted biopsies.
• Vaginal cancer is diagnosed by biopsy.

Keep learning in the app

Further reading (selection)

1. MSD Manual Professional: Vaginal Cancer
2. StatPearls: Vaginal Cancer

Cross-references