Genital human papillomavirus (HPV) infection is one of the most common sexually transmitted infections and the principal cause of cervical cancer. The broad goal of this study is to determine the detailed natural history of HPV infection, on a type/subtype specific basis, in a cohort unique for its long follow-up, large size and the fact that it is a truly representative (i.e., population-based) sample of an entire community. Approximately 10,000 women in a high-risk Costa Rican province were enrolled and have been followed approximately 7 years for development of incident high-grade CIN (and rare cancers). During the project, comprehensive repeat screening tests and cervical specimens for HPV DNA testing were obtained.
The specific aims of this project are to: (1) describe the detailed natural history of HPV infection on a type-specific and variant-specific basis. The prevalence, incidence and duration of HPV infection and risk factors for persistent infection and progression to high-grade CIN in different age groups will be defined; (2) investigate the elevated prevalence of HPV in postmenopausal women by performing a nested case-control study; (3) identify the genetic basis for the oncogenicity of high-risk HPV types and variants. We hypothesize that natural selection has resulted in the emergence of genetically related cancer-causing HPV types. The complete set of viral genotypes associated with high-grade disease and a set of comparison genomes will be determined and analyzed.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01CA078527-07
Application #
6744100
Study Section
Epidemiology and Disease Control Subcommittee 2 (EDC)
Program Officer
Starks, Vaurice
Project Start
1998-07-24
Project End
2008-04-30
Budget Start
2004-05-01
Budget End
2005-04-30
Support Year
7
Fiscal Year
2004
Total Cost
$562,394
Indirect Cost
Name
Albert Einstein College of Medicine
Department
Pediatrics
Type
Schools of Medicine
DUNS #
110521739
City
Bronx
State
NY
Country
United States
Zip Code
10461
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Clarke, Megan A; Gradissimo, Ana; Schiffman, Mark et al. (2018) Human Papillomavirus DNA Methylation as a Biomarker for Cervical Precancer: Consistency across 12 Genotypes and Potential Impact on Management of HPV-Positive Women. Clin Cancer Res 24:2194-2202
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Rodríguez, Ana Cecilia; Ávila, Carlos; Herrero, Rolando et al. (2017) Cervical cancer incidence after screening with HPV, cytology, and visual methods: 18-Year follow-up of the Guanacaste cohort. Int J Cancer 140:1926-1934
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Usyk, Mykhaylo; Zolnik, Christine P; Patel, Hitesh et al. (2017) Novel ITS1 Fungal Primers for Characterization of the Mycobiome. mSphere 2:
Gradíssimo, Ana; Burk, Robert D (2017) Molecular tests potentially improving HPV screening and genotyping for cervical cancer prevention. Expert Rev Mol Diagn 17:379-391
Mirabello, Lisa; Yeager, Meredith; Yu, Kai et al. (2017) HPV16 E7 Genetic Conservation Is Critical to Carcinogenesis. Cell 170:1164-1174.e6
Harari, Ariana; Chen, Zigui; Rodríguez, Ana Cecilia et al. (2016) Cross-protection of the Bivalent Human Papillomavirus (HPV) Vaccine Against Variants of Genetically Related High-Risk HPV Infections. J Infect Dis 213:939-47

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