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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA077318-10
Application #
7617626
Study Section
Special Emphasis Panel (ZRG1-HOP-N (03))
Program Officer
Starks, Vaurice
Project Start
1998-09-01
Project End
2011-03-31
Budget Start
2009-04-01
Budget End
2011-03-31
Support Year
10
Fiscal Year
2009
Total Cost
$857,678
Indirect Cost
Name
University of Hawaii
Department
Type
Organized Research Units
DUNS #
965088057
City
Honolulu
State
HI
Country
United States
Zip Code
96822
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Scott, Mark E; Shvetsov, Yurii B; Thompson, Pamela J et al. (2013) Cervical cytokines and clearance of incident human papillomavirus infection: Hawaii HPV cohort study. Int J Cancer 133:1187-96
Shiramizu, Bruce; Milne, Cris; Terada, Kevin et al. (2012) A Community-Based Approach to Enhancing Anal Cancer Screening in Hawaii's HIV-Infected Ethnic Minorities. J AIDS Clin Res 3:
Moscicki, Anna-Barbara; Schiffman, Mark; Burchell, Ann et al. (2012) Updating the natural history of human papillomavirus and anogenital cancers. Vaccine 30 Suppl 5:F24-33
Goodman, Marc T; McDuffie, Katharine; Hernandez, Brenda Y et al. (2011) The influence of multiple human papillomavirus types on the risk of genotype-concordant incident infections of the anus and cervix: the Hawaii HPV cohort study. J Infect Dis 203:335-40
Shvetsov, Yurii B; Hernandez, Brenda Y; Wilkens, Lynne R et al. (2010) Plasma micronutrients and the acquisition and clearance of anal human papillomavirus infection: the Hawaii HPV cohort study. Cancer Res 70:9787-97
Goodman, Marc T; Shvetsov, Yurii B; McDuffie, Katharine et al. (2010) Sequential acquisition of human papillomavirus (HPV) infection of the anus and cervix: the Hawaii HPV Cohort Study. J Infect Dis 201:1331-9
Hernandez, Brenda Y; Wilkens, Lynne R; Thompson, Pamela J et al. (2010) Acceptability of prophylactic human papillomavirus vaccination among adult men. Hum Vaccin 6:467-75
Shvetsov, Yurii B; Hernandez, Brenda Y; Wong, Sze H et al. (2009) Intraindividual variability in serum micronutrients: effects on reliability of estimated parameters. Epidemiology 20:36-43
Shvetsov, Yurii B; Hernandez, Brenda Y; McDuffie, Katharine et al. (2009) Duration and clearance of anal human papillomavirus (HPV) infection among women: the Hawaii HPV cohort study. Clin Infect Dis 48:536-46

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