Immunohistochemical and ultrastructural evidence of papilloma virus infection associated with in situ and microinvasive squamous cell carcinoma of the vulva

Of 21 patients with predominantly intraepithelial carcinoma of the vulva, 14 had coexisting papilloma virus (PV)-related cytopathic changes in the neoplastic and non-neoplastic epithelial cells. A PV species-nonspecific internal capsid antigen (PV-Ag) was detected in 64% of the cases in a variable number of nuclei by avidin-biotin complex-immunoperoxidase tests. Intranuclear viral particles were identified in 44% of specimens by electron microscopy. The main clinicopathologic features were the gross appearance of multiple papillary growths or, less often, of giant condyloma, the young age of the patients (75% of whom were less than 40 years old), the association in 57% of the cases with simultaneous intraepithelial neoplasia of the cervix or perineal skin, and an incidence of recurrences in 28%. PV infection of the genital area recurred in 14% of the cases. Nodal metastases of squamous cell carcinoma were observed in two cases. The histopathologic features and the main characteristics in terms of natural history of this PV-associated neoplasia are very similar to so-called bowenoid carcinoma and different from those of verrucous carcinoma of the vulva, six cases of which were investigated for comparison. In the latter, the search for PV-Ag was consistently negative, the patients were much older, and metastatic nodal involvement was absent.