Vaginal Intraepithelial Neoplasia

Vaginal intraepithelial neoplasia (VaIN) is a premalignant squamous lesion of the vaginal epithelium. It is rare (0.2 to 0.3 per 100,000 women per year).

It is graded VaIN 1 (low grade; LSIL), and VaIN 2 and 3 (high grade; HSIL). Most are HPV related (HPV 16 in about 50 to 60% of VaIN 2 and 3). Lesions are frequently multifocal, and about 80% are in the upper third of the vagina, near the vaginal vault.

Risk factors: history of cervical intraepithelial neoplasia or cervical cancer (about 65%), previous hysterectomy for CIN, immunosuppression (HIV, transplant), smoking, prior pelvic radiation, and in utero DES exposure.

Progression of VaIN 3 to invasive vaginal cancer is about 5 to 10%. VaIN 1 often regresses (about 80%).

• Usually asymptomatic, detected by abnormal cytology (post-hysterectomy vault cytology or cervical cytology with normal colposcopy of the cervix)
• Occasionally postcoital bleeding or discharge
• Colposcopy: acetowhite epithelium, punctation, mosaic, or abnormal vessels, with Lugol iodine non-staining lesions; vaginal folds and vault angles (after hysterectomy) may hide lesions

• Abnormal cytology or HPV result with a normal appearing cervix or post-hysterectomy
• Colposcopy of the entire vagina with 3 to 5% acetic acid and Lugol iodine, and directed punch biopsy (histology confirms VaIN grade; p16 staining assists in separating HSIL from mimics)
• Evaluate the cervix, vulva and perianal region (field disease)
• Exclude invasive cancer: deep biopsy, and examination under anaesthesia if suspicious
• HPV genotyping and HIV testing

• VaIN 1: observation with repeat cytology, HPV test and colposcopy at 6 to 12 months (most regress).
• VaIN 2 and 3 (HSIL): treatment options (all with recurrence about 10 to 30%):
  • Topical imiquimod 5% cream (self-applied, 3 times weekly at night for 8 to 12 weeks; clearance about 60 to 85%)
  • Topical 5-fluorouracil 5% cream (once weekly for 10 to 12 weeks or 1.5 g twice weekly; risk of ulceration; protect the vulva with petroleum jelly)
  • CO2 laser ablation (success about 75 to 90%; depth 1.5 mm; suitable for multifocal disease, with the risk of vaginal stenosis and fibrosis)
  • Wide local excision or partial vaginectomy (upper vaginectomy, particularly for lesions in vaginal vault angles, after hysterectomy; gives a pathological specimen to exclude occult invasion in about 12 to 28% of VaIN 3)
  • Intravaginal brachytherapy (for refractory, extensive VaIN 3 in patients unfit for surgery; high dose rate; side effects include stenosis and atrophy)
  • Cavitational ultrasonic surgical aspiration (CUSA) as an alternative

• Vaginal oestrogen cream in postmenopausal women to improve epithelial healing and colposcopic evaluation.
• Follow up: cytology and colposcopy at 3 to 6 months, then every 6 to 12 months for 2 years, with HPV testing; then annual screening for at least 20 years (lifelong in high risk).
• HPV vaccination may reduce recurrence.