This project will establish a multiethnic cohort of women for long-term follow-up to identify factors that influence the persistence or resolution of human papillomavirus (HPV) infection of the uterine cervix.
The specific aims are to 1) study the association of the dietary intake of fruits and vegetables, and the plasma levels of carotenoids, alpha-tocopherol, and vitamin C with HPV persistence; 2) examine the role of HPV type, quantity (viral load), and multiple (synchronous) HPV infections in HPV persistence; and 3) examine the interaction between nutritional (e.g., beta-carotene) and viral (e.g., HPV 16) factors on the risk of persistent HPV infection. A multiethnic cohort of 1,152 HPV-positive women, aged 18 and older, will be established among patients attending the obstetrics and gynecology clinics of three large medical centers in Honolulu. The cohort will include appreciable numbers of Asian (Japanese, Filipino, Chinese, Korean) Polynesian (Hawaiian, Samoan) and Caucasian women. The cohort will be followed longitudinally with the following data collected at baseline, month 4, month 8, month 12, month 24 and month 36 (6 visits): (a) a cervical cytological (Pap) smear for pathological review; (b) colposcopic visualization of the cervix for confirmation of cytology; (c) a cervical sample for HPV DNA analysis; and (d) a blood sample to measure micronutrient levels. An abbreviated questionnaire will be administered at baseline and an expanded interview will be conducted at month 4 including information on diet, tobacco and alcohol use, and sexual and reproductive history. A diet history and follow-up interview will be conducted at each annual visit. Cervical biopsy specimens obtained from cohort members will be reviewed by the study pathologist and sections will be archived at no cost to the present study. Analysis of the data will focus on the evaluation of dietary and plasma micronutrient levels and viral characteristics that influence the persistence of HPV infection using a generalized estimating equation (GEE) approach that corrects for the correlation between the repeated measures. The identification of these factors may provide insight into the natural history of HPV infection, and may improve our ability to characterize women who are at greatest risk for developing HPV-associated neoplasia. Such knowledge may also assist in the development of appropriate screening strategies involving HPV DNA detection that could be targeted at women who would benefit most from intensive follow-up.
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