1025 INDUCTION OF UTERINE CARCINOMA BY HERPES SIMPLEX VIRUSES TYPES 1 AND 2 (HSV-1 AND HSV-2) IN THE MOUSE

Abstract

Epidemiological studies support the hypothesis that genital infection by HSV-2 is a cause of cervical (cerv) carcinoma (ca). Presumably a long latent period occurs between infection and onset of malignant changes. These studies also indicate that cerv ca has the epidemiological characteristics of a venereal disease, including sexual activity at a young age and with multiple partners. This suggests that genital HSV-2 infection acquired by sexually active adolescents may be the initiating event that results in cerv ca in adult life. There is no conclusive evidence in humans or animals, however, that cerv ca is the direct effect of genital exposure to HSV-2. The objective of this study, therefore, was to determine if exposure of the mouse cervix to HSV-1 or 2 induces cerv ca. C57 mice were exposed to formalin or ultraviolet-inactivated HSV-1 or 2 by insertion of virus-saturated cotton pledgets into the vagina 5 times a week for 80 weeks. This was felt to simulate the conditions of latent infection. Control mice were exposed to cell culture fluids without virus. Pap smears for cerv cytology were obtained biweekly. Cerv dysplasia progressing to invasive ca occurred in 24-60% of virus-exposed mice. Endometrial ca was detected in 7-28% of exposed mice. All controls remained normal. It was concluded that in the mouse prolonged exposure of the female genital tract to inactivated HSV-1 or 2 induces cerv dysplasia and ca and, less frequently, endometrial ca. Histologically these lesions were the same as those in humans.