Prevalence of Human Papillomavirus Genomes in Tissues from the Lower Genital Tract as Detected by Molecular In Situ Hybridization

Abstract

Incidence cases of human papillomavirus (HPV)-related disease of the lower anogenital tract were prospectively collected and submitted to RNA-DNA in situ hybridization, which allows a direct correlation between morphology and the presence of viral DNA. The overall HPV detection rate in condylomata and intraepithelial or invasive neoplasia varied for the different genital areas: cervix (64%), vagina (56%), vestibule (59%), vulva (50%), and penis (42%). HPVs 6/11 were associated with condylomata, whereas HPV 16 was associated with intraepithelial and invasive neoplasia. Not a single case of intraepithelial or invasive neoplasia contained HPV 6/11, which supports the notion of the oncogenic potential of HPV 16. Condylomata were positive for HPV 16 only when adjacent to HPV 16-positive cervical intraepithelial neoplasias (CINs). The amount of viral DNA (copy number) was low in invasive cancers, intermediate in intraepithelial neoplasia, and conspicuously high in condylomata. In biopsies (n = 142) taken from lesions suggestive of subclinical papillomavirus infection on the basis of minor colposcopic and histologic abnormalities, HPV DNA was not detectable. Histologically normal tissue (n = 210) adjacent to condyloma, CIN, or cancer, and thus potential carrier of latent HPV infection, also proved negative for HPV DNA by in situ hybridization. The inability to detect viral DNA by in situ hybridization in tissues diagnosed as subclinically or latently infected may have been due to limited sensitivity of the hybridization method applied in this study.