Epidemiologic research conducted over the past couple of decades has shown that infection with the human papilloma virus (HPV) is a cause of most cases of cervical cancer. Prospective studies have shown that women infected with HPV are more likely to develop cervical intraepithelial neoplasia (CIN), and that those with persistent oncogenic type HPV infections are at a significantly increased risk of developing CIN compared with women transiently infected. In addition, persistently HPV positive women appear to be four times more likely to have persistent cervical lesions. Although HPV infection is a cause of cervical cancer, it may be an insufficient cause requiring the presence of other factors for the infection to progress to a significant cervical lesion. Nutritional status may be an important cofactor affecting both HPV persistence and progression of persistent HPV infection to CIN. However, the association between nutritional status and cervical carcinogenesis has not been adequately tested. The overall goal of this application is to determine, using prospectively collected HPV and cytology data, the association between serum carotenoid and tocopherol status and cervical carcinogenesis among a cohort of high risk study participants in the Brazilian HPV Natural History Cohort (RO1 CA70269). This project will provide the first prospective analysis of serum carotenoid and tocopherol concentrations and risk for persistent HPV infection; it will be based on sensitive and specific methods for assessing type of HPV infection over a 12 month period, and evaluate subsequent 5 year risk of progression to CIN. This proposed study is unique in that if focuses on early events in cervical carcinogenesis: HPV infection, HPV persistence, and progression to CIN. It is cost-effective, utilizing previously collected serum samples and questionnaire data. The study utilizes state of the art methods for determining both PV status and serum carotenoid and tocopherol status. Furthermore, it incorporates multiple measurements of both HPV status and serum nutrient concentrations minimizing the probability that measurement imprecision resulting from temporal fluctuations will obscure the true association between nutrients status, and HPV persistence and risk of CIN. Results from this study will efficiently further our understanding of the role of antioxidant nutrients and cervical carcinogens.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA081310-03
Application #
6513545
Study Section
Epidemiology and Disease Control Subcommittee 2 (EDC)
Program Officer
Starks, Vaurice
Project Start
2000-06-16
Project End
2004-05-31
Budget Start
2002-06-01
Budget End
2004-05-31
Support Year
3
Fiscal Year
2002
Total Cost
$386,149
Indirect Cost
Name
University of Arizona
Department
Miscellaneous
Type
Schools of Public Health
DUNS #
City
Tucson
State
AZ
Country
United States
Zip Code
85721
Siegel, Erin M; Patel, Nitin; Lu, Beibei et al. (2012) Circulating biomarkers of iron storage and clearance of incident human papillomavirus infection. Cancer Epidemiol Biomarkers Prev 21:859-65
Siegel, Erin M; Patel, Nitin; Lu, Beibei et al. (2012) Biomarkers of oxidant load and type-specific clearance of prevalent oncogenic human papillomavirus infection: markers of immune response? Int J Cancer 131:219-28
Richardson, Lyndsay A; Tota, Joseph; Franco, Eduardo L (2011) Optimizing technology for cervical cancer screening in high-resource settings. Expert Rev Obstet Gynecol 6:343-353
Siegel, Erin M; Salemi, Jason L; Craft, Neal E et al. (2010) No association between endogenous retinoic acid and human papillomavirus clearance or incident cervical lesions in Brazilian women. Cancer Prev Res (Phila) 3:1007-14
Siegel, Erin M; Salemi, Jason L; Villa, Luisa L et al. (2010) Dietary consumption of antioxidant nutrients and risk of incident cervical intraepithelial neoplasia. Gynecol Oncol 118:289-94
Siegel, Erin M; Craft, Neal E; Duarte-Franco, Eliane et al. (2007) Associations between serum carotenoids and tocopherols and type-specific HPV persistence: the Ludwig-McGill cohort study. Int J Cancer 120:672-80
Siegel, Erin M; Craft, Neal E; Roe, Denise J et al. (2004) Temporal variation and identification of factors associated with endogenous retinoic acid isomers in serum from Brazilian women. Cancer Epidemiol Biomarkers Prev 13:1693-703
Flores-Munguia, Roberto; Siegel, Erin; Klimecki, Walter T et al. (2004) Performance assessment of eight high-throughput PCR assays for viral load quantitation of oncogenic HPV types. J Mol Diagn 6:115-24
Giuliano, Anna R; Siegel, Erin M; Roe, Denise J et al. (2003) Dietary intake and risk of persistent human papillomavirus (HPV) infection: the Ludwig-McGill HPV Natural History Study. J Infect Dis 188:1508-16