Vulvar Intraepithelial Neoplasia

Vulvar intraepithelial neoplasia (VIN) is a premalignant squamous or glandular lesion of the vulvar epithelium. Two squamous types are recognised, with different aetiology, age group and progression risk.

• High grade squamous intraepithelial lesion (usual type VIN) is caused by persistent high risk human papillomavirus infection, with type 16 in about 75 to 80 percent. It affects women aged 30 to 50 years and is often multifocal. It is associated with cervical and vaginal neoplasia, smoking and immunosuppression (HIV, transplant).
• Differentiated VIN is HPV-independent and arises in chronic inflammatory dermatoses (lichen sclerosus, lichen planus). It is seen in older women and is usually unifocal. It carries a high and rapid risk of progression to keratinising squamous carcinoma, and p53 mutation is common.
• Low grade squamous intraepithelial lesion is a flat condyloma or HPV effect and is not premalignant.

Untreated high grade lesions progress to invasive cancer in about 6 to 10 percent over years. Spontaneous regression occurs in young women. Paget disease of the vulva is a separate intraepithelial adenocarcinoma.

• Pruritus (the commonest symptom), burning, pain, or an incidental finding.
• Lesions are white, red, pigmented (brown or black) or skin coloured, flat or raised, papular or plaque like, single or multifocal, on hairy or non-hairy skin, perineum and perianal region. Differentiated VIN may look like non-specific white or red areas on a background of lichen sclerosus and can be ulcerated or hyperkeratotic.
• Signs of lichen sclerosus (atrophy, fusion of labia, clitoral hood scarring, fissuring) in differentiated VIN.
• Associated lower genital tract disease: cervical, vaginal and anal intraepithelial neoplasia.

• Inspection of the vulva, perineum, perianal skin and vagina, using good light and, where available, colposcopic magnification after 5 percent acetic acid application.
• Punch biopsy (4 to 6 mm) under local anaesthesia of every suspicious lesion before treatment; excision biopsy for large or ulcerated lesions to exclude invasion. Multiple biopsies are needed in multifocal disease.
• Histology: basal and parabasal atypia extending through the epithelial thickness in high grade disease (p16 positive); basal atypia with abnormal maturation and premature keratinisation in differentiated VIN (p16 negative, abnormal p53 pattern).
• Cervical cytology, high risk HPV testing, colposcopy of cervix and vagina, and anal examination.
• HIV test in appropriate patients.

Treatment depends on the type, the extent and site, and the wish to preserve anatomy and sexual function.

• Differentiated VIN and any lesion suspicious of invasion: wide local excision with 5 to 10 mm margins, as the risk of progression is high.
• Control lichen sclerosus as part of management. Use clobetasol propionate 0.05 percent ointment nightly for 4 weeks, alternate nights for 4 weeks, then twice weekly as maintenance.
• High grade squamous intraepithelial lesion, local unifocal disease: wide local excision (5 mm margin) or laser vaporisation, after biopsy has excluded invasion. Vaporise to 1 to 2 mm depth on non-hairy skin and 3 mm on hair bearing skin.
• Margin involvement increases recurrence, to about 50 percent versus 20 percent with clear margins. Re-excision is not mandatory if the patient is asymptomatic and can be followed.
• Multifocal or extensive disease, or when preserving anatomy is a priority: imiquimod 5 percent cream. Apply three times weekly (Monday, Wednesday, Friday) at night for up to 16 weeks, building up from once or twice weekly. Wash off after 8 to 10 hours.
• Imiquimod response rates are 50 to 80 percent complete or partial. Expect local inflammation, erosion and pain. Cidofovir 1 percent topical is an alternative.
• Laser or cavitational ultrasonic surgical aspiration may be used for extensive clitoral or perianal disease.
• Vulvectomy is rarely needed and avoided because of its psychosexual consequences.
• Imiquimod is not used in pregnancy.
• Follow up with examination at 3 and 6 months after treatment. Then review every 6 to 12 months for at least 5 years, and in many cases lifelong.
• Recurrence rates reach 30 to 50 percent. They are higher with multifocal disease, immunosuppression and smoking.
• Differentiated VIN needs ongoing lichen sclerosus control and regular review.
• Advise smoking cessation and HPV vaccination, which does not treat existing lesions but reduces new disease. Screen the cervix and anus.
• Immunosuppressed women have higher recurrence and progression and need closer follow up.