This is a revised proposal to continue a case-control study to test the hypothesis that infection with human papilloma virus (HPV) is related to an increased risk of cervical intraepithelial neoplasia III (CIN III/carcinoma-in-situ). In addition, this study will investigate the presence and possible involvement of other sexually transmitted infectious agents (such as HSV-II, CMV, and chlamydia) and other exposures (including smoking, contraceptive use, and nutrition). This population-based case-control study will continue to identify and interview women with biopsy-proven CIN III who are residents of the three urban counties of western Washington, 45 years old or less, and enrolled in Group Health Cooperative (GHC), one of the largest HMOs in the United States. Control women of the same ages and counties of residence will be randomly selected through enrollment files of GHC and interviewed. All previous cytologic specimens (Pap smears) and cervical biopsies of cases and controls will be collected and evaluated for presence of HPV types by means of Polymerase Chain Reaction (PCR). Blood samples will be collected from both cases and controls and analyzed for evidence of prior exposure to sexually transmitted viral infections. This study was initially approved and funded for a two-year pilot phase as part of a program project grant (CA 42792) on HPV. This revised proposal addresses concerns by reviewers about the use of the PCR method to measure the presence of HPV in Pap smears. Since its inception, the PCR has become recognized as the most sensitive method of measuring HPV in epidemiologic studies and is the ONLY method available for studies such as this which rely on archival specimens, such as Pap smears.
