Vulvar intraepithelial neoplasia: age, morphological phenotype, papillomavirus DNA, and coexisting invasive carcinoma

Recent studies suggest that subsets of vulvar intraepithelial neoplasia (VIN) may be distinguished based on morphological presentation, the presence or absence of human papillomavirus (HPV) nucleic acids, and patient age. We analyzed 65 VIN lesions, including 15 with associated squamous cell carcinoma, to determine the relationship between pathological parameters associated with common types of VIN (multinucleation, koilocytosis, verruco-papillary morphology, diffuse atypia), rarer variants (differentiation, basal atypia), patient age, and papillomavirus nucleic acids. For all lesions higher mean ages were observed in patients with lesions that were associated with cancer and with well differentiated VIN variants with basal atypia only. A strong negative correlation with HPV nucleic acids was observed for differentiated variants with basal atypia (P = .002). In the common or "classic" VIN group patients with lesions with koilocytotic atypia, multinucleation, and verruco-papillary morphology were generally younger. However, no parameter or group of parameters defined a subset of patients with a significantly lower mean age or lesions with a higher index of HPV nucleic acids. Three of six lesions of lichen sclerosus (LS)-associated VIN, including one involving invasive carcinoma in elderly women, contained HPV nucleic acids; all three lesions exhibited the features of classic VIN. The finding of HPV across a broad age range suggests that this virus may play a role in vulvar neoplasia at any point in life. The direct demonstration of HPV nucleic acids within three LS-associated VINs is intriguing because it links two distinct risk factors to the same neoplasm.