Immunophenotypic and viral (human papillomavirus) correlates of vulvar seborrheic keratosis

Human papillomavirus (HPV) infections of the genital mucosa classically present as warts (condylomata) and are traditionally defined by the presence of viral cytopathic effect (koilocytosis). In recent years, HPV has been detected in vulvar epithelial changes lacking koilocytosis, including squamous papillomas and lesions closely resembling seborrheic keratosis (SK). The purpose of this study was to determine the frequency and type of HPV associated with vulvar SK (VSK) and to compare expression of biomarkers (p16, Mib-1, and cyclin E) in these lesions. Sixty-seven biopsy specimens, including 25 VSKs, 10 nondiagnostic vulvar acanthoses, 12 fibroepithelial polyps (FEPs), and 20 nongenital cutaneous SKs (CSKs), were studied. Biopsy specimens were typed for HPV by polymerase chain reaction and immunostained with Mib-1, cyclin E, and p16^INK4 antibodies. Eighteen of 25 VSKs (72%), 0 of 10 nondiagnostic vulvar acanthuses (0%; P = 0.0001), 2 of 12 FEPs (16.7%; P = 0.004), and 3 of 20 CSKs (15%; P = 0.0002) scored HPV positive. Increased Mib-1 staining was significantly more common in VSKs than in other vulvar lesions, but not in CSKs; increased p16 and cyclin E staining was not more common. VSKs are morphologically and immunophenotypically similar to CSKs but distinct by their association with HPV. Unlike the cervix, p16 and cyclin E will not consistently distinguish VSKs from HPV-negative lesions due to underexpression in low-risk HPV infections (p16) and less-restricted expression in vulvar lesions (cyclin E). Whether CSKs are associated with other forms of HPV infection remains to be determined.