Viral agents in two-stage cervical carcinogenesis: an experimental study in mice

The role of chemical and viral agents in the development of cervical cancer in mice was studied by repeated carcinogen applications, repeated intravaginal instillations of HSV type II virus, and single carcinogen application as initiating agent followed by repeated instillations of virus as promoter. In all the animals studied, repeated applications of 9,10-dimethylbenzanthracene (DMBA) induced dysplastic conditions of the cervix and vagina, mild, moderate, and severe, as well as a large number of invasive squamous cell carcinomas. DMBA alone as initiating agent did not induce tumors or marked dysplasia; when followed by repeated applications of HSV2 virus only mild dysplastic lesions occurred. Repeated applications of HSV2 alone produced inflammatory changes of the cervix and vagina. It is concluded that repeated intravaginal instillation of HSV2 virus as done in this study does not induce cervical cancer or its precursors, and in a two-stage system is only weakly a promoter of carcinogen-induced latent tumor cells.