ROLE OF PAPILLOMAVIRUS IN CERVICAL NEOPLASIA

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Recent molecular virologic and immunologic studies have shown a relationship between human papillomavairus (HPV) infection and dysplasia of the uterine cervix. The significance of these observations is underscored by the fact that dysplasias are considered precursor lesions to cervical carcinoma. The specific aims of this proposal are to characterize HPV sequences from dysplasias by molecular cloning for the purpose of identifying the various HPV types associated with these lesions using molecular hybridization and immunological tests with antibodies directed against virus type-specific poly- or oligopeptides. HPV sequences will be cloned into plasmid or Charon vectors and subsequently characterized by hybridization to DNAs of known HPV types. These cloned DNAs will be used in blot transfer and in situ hybridization experiments with dysplasias and cervical carcinomas. Sequence analysis of the viral DNAs will provide necessary information for the synthesis of virus type-specific structural polypeptides in bacterial expression vector systems or synthesis of oligopeptides by solid-phase chemistry. The resultant antibodies will be used to screen biopsy specimens to determine the HPV type associated with dysplasias which regress and those which progress to more serious disease. Antibodies directed against papillomavirus genus-specific nonstructural (transforming) proteins will be synthesized in bacteria for use in immunocytochemical studies on cervical cancers. From the behavior of cervical dysplasia (regression or progression) it would be of prognostic and/or diagnostic value to be able to predict the outcome of HPV infection of the cervix. Such information could provide a more rational approach to the management of cervical neoplasia.