HUMAN PAPILLOMAVIRUS AND PROGNOSIS OF FEMALE ANOGENITAL CANCER

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Although cervical cancer mortality has declined substantially in past decades, the prognosis for the average woman diagnosed with this malignancy has not improved. This may be due in part to the paucity of markers beyond those traditionally employed (e.g., stage, nodal status) that are predictive of prognosis and thus could be used to refine the selection of patients for optimal treatment. This project will test hypotheses regarding the association of selected tumor markers and patient characteristics with the prognosis of invasive cervical carcinoma and other female anogenital carcinomas (vulvar, vaginal, and anal). In particular, we will determine whether the risks of recurrence and/or survival of these neoplasms are related to l) detection of human papillomavirus (HPV) DNA in tumor tissue; 2) serum antibody response to HPV proteins, and 3) patient characteristics. In addition, for cervical carcinoma we will assess the relationship between prognosis and tumor expression of the following markers: p53 tumor suppressor gene and c-myc oncogene products, estrogen and/or progesterone receptors, and measures of tumor cell proliferation (Ki-67 proliferation associated antigen) and apoptosis (bcl-2 oncogene and TdT-mediated dUTP-biotin nick end labeling). These aims will be achieved through a series of tumor site-specific case- cohort studies among all female patients eligible for past and proposed population-based case-control studies of anogenital cancer funded through the Program Project Grant (PPG). From among cohorts of women diagnosed with each anogenital cancer between January 1, 1986 and December 31, 1996, we will 1) identify all deaths and recurrences occurring through 1997, and 2) select a random sample to serve as the comparison sub-cohort. For all cases and sub-cohort members, fixed paraffin-embedded malignant tumor tissue will be obtained, processed, and analyzed in slide-based immunoperoxidase (cervical carcinoma) and PCR studies (all anogenital carcinomas). Information on personal characteristics will be obtained from in-person interviews conducted as part of Project 3, or abstraction of medical records conducted within the scope of this proposal. Proportional hazards models will be used to estimate the relative risk of recurrence and death associated with the factors under study. The results of this investigation have the potential to provide physicians and patients with information that could be used to guide the choice of the most appropriate treatment for anogenital carcinoma among women.