During the past five years, we have established a multiethnic cohort of women for long-term follow-up to identify factors that influence the persistence of human papillomavirus (HPV) infection of the uterine cervix. Preliminary analyses of our data suggest that reduced dietary and plasma levels of certain micronutrients, such as carotenoids, may enhance the persistence of oncogenic HPV infection. Although the precise mechanism for this inverse association is unknown, failure to clear the virus results in the induction of proinflammatory cytokines, such as interleukin (IL)-1, which increases cellular vulnerability to DNA, protein and lipid damage. We hypothesize that dietary components that possess antioxidant and DNA repair properties will protect immune cells from oxidative damage and reduce HPV persistence.
Our specific aims are to 1) evaluate the effect of dietary and/or plasma concentrations of carotenoids, tocopherols, vitamin C and B complex vitamins on incident oncogenic HPV infection, oncogenic HPV persistence, and SIL of the cervix; 2) examine the influence of local cervical mRNA levels of IL-1alpha, IL-1beta, and tumor necrosis factor (TNF)-alpha on the persistence of oncogenic HPV infection; and 3) examine the joint association of dietary and immunological markers on the persistence of oncogenic HPV infections of the cervix. A multiethnic cohort of 751 oncogenic HPV DMA-positive women will be followed during a five year period. Interviews and biological specimens will be collected at baseline and at four month intervals for a minimum of four visits in one year and a maximum of 16 visits in five years. At each visit a gynecologic examination will be performed and the following specimens will be collected: a) endocervical specimens for cytokine mRNA detection, HPV DNA analysis, a cytological (Pap) smear, and future detection of C. trachomatis and Herpes Simplex Virus-2; b) a fasting blood sample to measure micronutrient levels; c) an endocervical specimen by Merocel ophthalmic sponge for future cytokine protein detection; and d) an anal sample for future detection of HPV. A follow-up interview will be conducted at each visit; a diet history will be repeated annually. Statistical analyses of data collected in both grant cycles will focus primarily on the evaluation of dietary and plasma micronutrient levels and immune characteristics that influence the persistence of HPV infection. Increased knowledge of the role of nutrition and the inflammatory response in HPV persistence will help us to better understand the responsiveness to HPV vaccines, may assist in the development of novel therapies, and may provide a fuller picture of the host's reaction to HPV infection.
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