Clinical Review

Be vigilant for vulvar intraepithelial neoplasia— here is why

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Differentiated VIN exhibits more subtle atypia, with keratin pearls and an eosinophilic cytoplasm.

Biologically, usual-type VIN is associated with HPV and linked to smoking and sexual activity, as we discussed. As its name suggests, it is found more frequently than differentiated VIN. It is most common in women in their late 30s to early 50s.

In contrast, differentiated VIN is not associated with HPV and is more common in postmenopausal women; it is frequently seen with lichen sclerosus.

OBG Management: When did this new way of classifying VIN—as usual-type and differentiated—originate?

Dr. Massad: The ISVVD classification system changed in 2004. Before then, it paralleled the CIN classification system, with three grades of intraepithelial neoplasia corresponding to the thickness of the epithelium filled by dysplastic cells: VIN 1, 2, and 3. However, VIN 1 was not really neoplastic. It reflected infection with HPV, and although it might progress to higher-grade dysplasia or cancer, the risk was minimal. So the ISVVD revised the classification system to include only high-grade VIN—the old VIN 2 and VIN 3. HPV-associated lesions with dysplastic cells confined to the lower third of the epithelium are managed like genital warts, with observation for spontaneous regression or treatment with topical therapy or surgery.

How to screen for VIN

OBG Management: What screening strategy is recommended for VIN?

Dr. Massad: There is no such recommendation. Screening for VIN hasn’t been implemented for several reasons. Most important, other than inspection of the vulva by a clinician, there is no good screening test. VIN isn’t very common, so mass inspection for lesions is unlikely to be cost-effective. The sensitivity and specificity of inspection by a clinician aren’t known. Most lesions are found by women, their partners, or clinicians before cancer develops. And most disease is treated before cancer arises.

OBG Management: Isn’t there a need for heightened scrutiny of the vulva?

Dr. Massad: Yes. Women should examine their genitalia several times a year and seek attention if anything changes. That’s especially true for women who have risk factors, such as smoking, immunosuppression, and a history of being treated for cervical dysplasia. It’s the same concept we employ when teaching women to identify early breast lesions through self-examination.

The biggest challenges in detecting VIN are educating women to report vulvar skin changes to their clinicians for assessment and educating clinicians to examine the vulva before inserting the speculum for cervical screening and vaginal inspection.

OBG Management: Is another challenge distinguishing some forms of VIN from genital warts?

Dr. Massad: It can be a challenge, but clinicians should recall that warts are most common among women around the time of the onset of sexual activity. Older women sometimes develop warts with a new sexual partner. However, when women in their 40s and older develop new warty lesions, always suspect VIN. A woman in her 60s or older who has a new, warty-appearing vulvar lesion should be assumed to have VIN or cancer.

OBG Management: Does VIN ever regress spontaneously?

Dr. Massad: Yes. There have been reports of spontaneous regression of VIN, especially in young women. Regrettably, there are also reports of progression to cancer during observation. There are no characteristics that allow us to distinguish lesions that are going to progress from those that will regress. The ACOG-ASCCP Committee Opinion recommends treatment of all VIN.1

Can VIN be prevented?

OBG Management: The Committee Opinion recommends that the quadrivalent HPV vaccine be offered to women “in target populations” because it can decrease the risk of VIN. What are those target populations?

Dr. Massad: The target population for HPV vaccination is 11- and 12-year-old girls, but catch-up vaccination is acceptable in patients as old as 26 years.

OBG Management: Why isn’t the bivalent vaccine recommended?

Dr. Massad: Only the quadrivalent vaccine has been approved by the US Food and Drug Administration (FDA) for prevention of VIN, although, in theory, the bivalent vaccine ought to be effective as well.

When to biopsy

OBG Management: Do you recommend that any suspect lesion on the vulva be biopsied?

Dr. Massad: The decision to biopsy should be individualized. However, women who have apparent warts that fail to respond to topical therapy should undergo biopsy, as should older women with warty lesions. Keep in mind that older women may develop verrucous carcinomas and may benefit from excision of enlarging warty lesions even if a biopsy is reported as only condylomata. Clinicians should not biopsy varicosities or obvious flat nevi.

OBG Management: Is colposcopy ever helpful in assessing vulvar lesions?

Dr. Massad: Most vulvar lesions can be identified without colposcopy, but colposcopy is useful in determining the extent of lesions. It often reveals subclinical disease not evident at the time of vulvar inspection.

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