Despite clear evidence that many sexually transmitted disease (STD) agents can infect the cervix acutely and/or chronically, and despite the many studies linking cervical neoplasia to several individual STD agents, a critical flaw in all previous studies in failure to control for sexual behavior or to simultaneously assess the relationship of cervical intraepithelial neoplasia (CIN) to each of the agents which have been implicated in this condition. Such analyses have been found to be essential in relating sTD agents to other syndromes linked with sexual activity. We propose a set of interdisciplinary and complementary approaches to study the relationship of cervicovaginal STD pathogens to various forms of cervical dysplasia, and to less severe but common forms of cervical atypia. The proposal includes qualitative and quantitative cytopathology, together with clinical, epidemiologic, microbiologic, biochemical, genetic, and serologic studies in two populations of patients: 1) women with a high prevalence of STD who are seen in an STD clinic, and 2) women with cervical atypia or CIN and controls seen in a university hospital-based population Having thus comprehensively characterized and stratified those with or without cervical atypia on the basis of type of atypia and type of associated STD, women from the STD clinic will then be followed longitudinally to compare the natural history of various categories of atypia and STD. Proposed new techniques, many developed by the investigators, to be used for classification of atypias and detecting STD pathogens, include: 1) monoclonal antibody and improved DNA probes for the detection of STD agents in cytologic smears and in biopsies; 2) monoclonal antibodies for identification of subcellular units to classify neoplastic lesions according to cell of origin; and 3) flow cytometry and densitometry for the measurement of cellular DNA content to identify lesions with malignant potential. State-of-the-art techniques for clinical evaluation of the cervix and vagina, for serodiagnosis, and for identification and quantitation of bacterial and viral pathogens will also be employed.
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