Cytologic and histologic manifestations of human papillomavirus infection of the female genital tract and their clinical significance.

The historical developments in the recognition of the role of human papillomavirus (HPV) infection in cells and tissues of the female genital tract are briefly summarized. The identification of a specific marker cell, the koilocyte, has led to initial studies of frequency and biologic significance of neoplastic lesions of the uterine cervix associated with HPV. By molecular virology techniques, over 40 types of HPV have been identified and their tissue affinity determined. Types 6, 11, 16, 18, and 31 are most commonly associated with anogenital lesions, among them a broad spectrum of cervical intraepithelial neoplasia (CIN). While current evidence suggests that lesions associated with HPV Types 6 and 11 are potentially less harmful to the patient than lesions associated with HPV Types 16 and 18 (which have been identified also in invasive cervical carcinomas and cell lines derived therefrom), a major long term prospective study may be required to confirm this view. A factor that complicates the issue still further is the recent observation that HPV DNA of all four types has been identified in 11% of women and 5.5% of men free of disease. Infection with multiple viral types (including Types 16 and 18) was common in this apparently healthy population. Although HPV must be considered as a prime candidate for a transforming virus, current evidence suggests that the infection with the virus is per se an insufficient condition for the development of precancerous lesions or cancer of the uterine cervix and that another factor or factors may be necessary for these events to take place. Some of these possible cofactors such as age, repeated infections, and the immune status of the patient are discussed. A great deal of additional work is required before the precise role of HPV virus in the genesis of carcinoma of the uterine cervix, vulva, and vagina is firmly documented.