Over the last five years we have enrolled 672 women into a prospective cohort study examining the role of specific types of HPV, other sexually transmitted pathogens, and other risk factors in the development of CIN 2-3. As of the present, these women have completed an average of 3.5 years of follow-up; 224 (33%) have undergone colposcopically-directed biopsy, and 256 (38%) remain in follow-up. We find that among sexually active young women: 1) cervical human papillomavirus (HPV) infection is common, but usually can not be detected after 8 months using southern transfer hybridization (STH) without PCR, 2) HPV 16 or 18 infection is associated with a surprisingly high and rapid rate of progression to CIN 2-3, 3) repeated detection of any type of HPV DNA is also associated with CIN 2-3 (adequate numbers for type- specific analyses not yet available), and 4) other sexually transmitted cervical pathogens, and young age at sexual debut (but not lifetime number of sexual partners) are independent risk factors for progression. We also find evidence for a possible interaction between HPV and other cervical pathogens for development of CIN 2-3. Over the next four years, by continuing to follow 250 women already enrolled in the study, by further analyzing stored specimens using both PCR-based assays and STH , and by enrolling and following an additional 250 women, we will extend our observations and address several additional questions. Specifically, we propose to further define how the risk of CIN 2-3 is influenced by patterns of viral shedding (detected by repeated testing using STH and PCR-based methods), and by cervical infection with other sexually transmitted pathogens. We plan to increase our sample of women who have cervical infection by """"""""low and intermediate risk"""""""" HPV 6, 11, 31, 33, 35, 42, 43, 44, 51, 52 to better define the risk of CIN 2-3 associated with these papillomavirus types. This study will not only provide needed information on the natural history of cervical HPV infection among those at high risk for cervical pathology, it will also provide new insights into how HPV detection methods may be used to augment cervical cancer prevention efforts.
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