Vulval intraepithelial neoplasia
What is vulval intraepithelial neoplasia?
Vulval (or vulvar) intraepithelial neoplasia is a pre-cancerous skin lesion of any part of the vulva. Usual-type vulval intraepithelial neoplasia (VIN) is associated with human papillomavirus (HPV) infection, and is now also called vulval high-grade squamous intraepithelial lesion (HSIL). In this article, we abbreviate the condition as VIN/HSIL.
- VIN/HSIL is an intraepithelial form of squamous cell carcinoma
- VIN/HSIL was previously known as Bowen disease of the vulva, but this term is no longer used.
- VIN/HSIL is not invasive cancer, but vulval cancer (squamous cell carcinoma, SCC) occurs in about 15% of women if VIN/HSIL is left untreated.
- The term VIN/HSIL excludes vulval extramammary Paget disease and vulval in-situ melanoma.
VIN associated with inflammatory diseases of the vulva, lichen sclerosus and erosive lichen planus (and not with HPV) is called differentiated VIN (dVIN) and accounts for 5% of intraepithelial squamous cell carcinoma.
How do VIN/HSIL and dVIN present?
Although some women do not have symptoms, VIN/HSIL and dVIN often present with:
- Mild to severe vulval itching
- Mild to severe vulval burning
- One or more slightly raised well defined skin lesions; these may be pink, red, brown and/or white in colour.
The lesions can occur on any part of the vulva, but are most frequently diagnosed on hair-bearing labia majora, and non-hair bearing labia minor and posterior fourchette. Most cases of dVIN occur on non-hair bearing skin.
Why do VIN/HSIL and dVIN occur and who is at risk?
VIN/HSIL and dVIN may occur in women of all ages, although currently an increased number of younger women (even teenagers) are presenting with VIN/HSIL. The average age of women with VIN/HSIL and dVIN is 45–50 years.
The following factors have been associated with VIN/HSIL.
- HPV causes about 60% of all cases of VIN/HSIL. HPV also causes genital warts and other genital cancers (cervical cancer, vaginal cancer and anal cancer). Only oncogenic types of HPV (especially types 16 and 18) are associated with VIN, and these don't always cause visible warts (which are mostly caused by types 6 and 11). About half of women with VIN/HSIL also have a history of abnormal cervical smears or cervical cancer.
- Smoking; it is thought that the cancer promoting agents in cigarettes are concentrated in the skin of the lower genital tract and smokers have a higher risk of VIN/HSIL than non-smokers.
- Immunosuppression by disease, such as human immunodeficiency virus (HIV) infection, or medications, such as those taken by organ transplant recipients.
How are VIN/HSIL and dVIN diagnosed?
The clinical appearance of an irregular red, white or pigmented plaque or plaques on the vulva may suggest a diagnosis of VIN/SIL or dVIN. Colposcopy (examination using magnification and a special light) may be used to see the extent of the condition. A skin biopsy is required to confirm abnormal epithelial cells in the epithelium, and to identify any invasive cancer.
- The epithelium may be hyperkeratotic (scaly) and acanthotic (thickened).
- HSIL reveals vacuolated and dysplastic cells with mitoses throughout the epithelium, which can include follicular epithelium.
- dVIN reveals dysplastic cells and mitoses confined to the basal layer.
- Immunohistochemistry stains: HSIL is p16 positive, and dVIN is p53 positive.
Warty lesions in postmenopausal women should undergo biopsy, particularly if they do not resolve with simple treatment.
Women with vulval lichen sclerosus and erosive lichen planus should be followed up carefully. Any areas failing to respond to high-potency topical corticosteroids, particularly if hyperkeratotic, should under biopsy in case of dVIN.
Classification of VIN/SIL
|1. Low grade squamous intraepithelial lesion (flat condyloma or HPV effect) (LSIL)|
|2. High grade squamous intraepithelial lesion (VIN usual type) (HSIL)|
|3. Intraepithelial neoplasia, differentiated-type (dVIN)|
HSIL and dVIN have potential to progress to invasive vulval cancer, whereas LSIL lesions are low risk and are not neoplastic. HSIL-associated cancers tend to be warty in appearance.
What treatments are available for VIN/HSIL?
LSIL does not always require treatment, but follow-up should be arranged until the lesions resolve, as they sometimes progress to VIN/HSIL.
VIN/HSIL and d-VIN are treated to reduce the risk of developing invasive cancer. The aim is to remove all affected tissue with a margin of apparently unaffected tissue. This may be done by surgical excision. Sometimes a complete vulvectomy (removal of the vulva) is undertaken because of the extent of disease or because of multifocal VIN/HSIL. Excision is undertaken for dVIN, which is rarely multifocal and can be more aggressive than VIN/HSIL.
If cancer is not suspected, laser ablation may be used in some centres, and is usually carried out under a general anaesthetic.
Medical therapy reported to be effective in at least some cases of VIN/HSIL, and is useful for treating a field area prone to multifocal disease. Options include:
- Imiquimod cream, applied 3 times weekly for 12 to 20 weeks. This results in red, inflamed and eroded tissue often accompanied by considerable discomfort.
- 5-fluorouracil cream, applied twice daily for several weeks. This causes quite severe inflammation (several weeks) and will not be tolerated by all women. It is less effective than imiquimod cream and thus is used less frequently than in the past.
- Photodynamic therapy (PDT) requires specialised equipment and can also be very painful.
- Therapeutic HPV vaccination.
- Cidovir has been described to be useful in some patients.
None of these medical treatments are officially approved for VIN/HSIL and are rarely recommended for dVIN.
Unfortunately VIN/HSIL recurs in at least one-quarter of patients. This is more likely if:
- The patient is immune suppressed
- The lesion was incompletely removed (positive margins on pathological report)
- Disease is multifocal.
Lichen sclerosus, which is associated with dVIN, is also a risk factor for recurrence.
Prevention of VIN/HSIL and dVIN
Women that have had genital warts or previous VIN/HSIL should be strongly encouraged to stop smoking.
What is the outcome for women with VIN/HSIL and dVIN?
If left untreated, LSIL usually resolves within a year or two. VIN/HSIL may turn into an invasive cancer in later years. On average it takes well over a decade for HPV-associated usual VIN/HSIL to progress to cancer, but cancer may develop more rapidly in dVIN. Untreated dVIN results in vulval cancer in 35–85% of cases.
Careful follow-up after treatment is essential long term. VIN/HSIL and dVIN may recur, particularly if excision margins are inadequate. Follow-up every 6–12 months is recommended for at least 5 years after surgery for VIN/HSIL and indefinitely for dVIN.
Up to 50% of women with VIN/HSIL develop cervical intraepithelial neoplasia (CIN), anal intraepithelial neoplasia (AIN), vaginal intraepeithelial neoplasia (VAIN) or invasive cancer of the genital tract or anus. It is particularly important to have regular cervical smears. Immune suppressed patients, especially those with HIV infection, should also undergo cytology of the anus.