Recent evidence indicates that precancerous conditions of the cervix (condyloma and cervical intraepithelial neoplasia or CIN) are closely related to human papillomavirus infections (HPV). Important questions remain regarding the venereal transmission of this virus, its distribution in cervical epithelium and the relationship of HPV to the development of precancerous and cancerous lesions of the cervix and lower female genital tract. If these questions could be answered it is conceivable that the sexual transmission of these viruses could be reduced and ultimately the incidence of CIN and invasive cancer could be reduced as well. Molecular studies of the relationship of papillomaviruses to neoplasia could provide insight into the mechanism of neoplastic transformation in the genital tract as well as other sites. The proposed project will analyze the molecular biology of HPV infection and early cervical neoplasis. Biopsies will be placed into biologic subsets using histological and DNA analysis and the papillomarvirus strains associated with these subsets will be determined through blot hybridization, restriction endonuclease analysis and molecular cloning. Lesions from sexual partners will be analyzed to determine if pairs of sexual partners share the same viruses and if these viruses cause the same epithelial lesions in men and women. The distribution of papillomaviruses will be explored with in-situ hybridization techniques to determine the distribution of the viral DNA in squamous lesions as well as normal squamous eppithelium. Expression of HPV RNA will be evaluated by DNA-RNA hybridization of lesions. In addition, to determine if HPV can induce transformation of cells, cell cultures will be cotransfected with HPV and oncogenes and monitored for morphologic transformation and analyzed for HPV RNA expression.
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