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

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Abstract
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.