Papillomavirus infections and human genital cancer

Abstract

Human papillomas are induced by at least eight distinct types of papillomaviruses. They are listed in Table 1. Condylomata acuminata, human genital warts, represent a group of fibropapillomatous benign tumors with exuberant exophytic growth which are induced by a papillomavirus (reviewed in [l]). They are mainly located at the foreskin of the penis, the glans, the vulva, the introitus vaginae, and intravaginally (see review [l]). They have also been reported on the cervix uteri, perianally, and even within the urethra [2-41. Epidemiological studies demonstrate a venereal mode of transmission [5]. They are prevalent in groups of high sexual promiscuity, such as homosexuals [3, 61 and prostitutes, and are by no means a rare disease. According to British statistics [7] they comprise 6.1% of all reported cases of venereally transmitted diseases (Table 2). Malignant conversion of condylomata acuminata has been reported repeatedly (reviewed in [l]). Anecdotal reports were published mainly from cases of long duration but exceptionally also from young individuals with a rather recent history of genital warts (reviewed in [l]). Malignant tumors developed within genital warts of the vulva, the penis, and also of the vagina. The role of the virus found electron microscopically in a few nuclei of the benign condylomata acuminata in the induction of such malignant tumors has not been established. Our own investigations on a possible role of human genital wart virus in genital cancer were initiated after a number of unsuccessful attempts to demonstrate herpes simplex type II DNA in biopsies of such tumors by nucleic acid hybridization [8]. Since epidemiological features of genital cancer point in a number of parameters (reviewed in [9]), such as dependence on the number of sexual partners, early onset of sexual relations, existence of marital clusters, and correlation in the incidence between cervical and penile cancer [9-151, to an infectious etiology, we started to analyze additional candidate viruses for their possible involvement in this disease. The presence of a virus belonging to a group of clearly oncogenic agents in genital warts and occasional reports on their malignant conversion stimulated the interest in these viruses. Initial experiments were designed to clarify the question of whether the papillomavirus found in genital warts is identical with papillomaviruses observed in other skin papillomas. This led to the identification of distinct types of papil-