Cervical cancer etiology is better understood than the origins of most major malignancies. Within the Division of Cancer Epidemiology and Genetics, several groups continue to study the most interesting and important research topics. In the HPV Guanacaste Study and the ALTS project, remaining topics in natural history of the causal virus (human papillomavirus, HPV) are the focus, as well as new methods comparisons. The unusually high prevalence of HPV in sub Saharan Africa is the focus in the Nigeria Project Itoju. Cervical Visualization Project: In this set of studies, HPV natural history is assessed visually (using a web-based open-source software system developed with the National Library of Medicine), microscopically (cytology and histology) and using a variety of molecular biomarkers. HPV Genome Project. Viral genomic studies are designed to determine why certain types of HPV, if persistent, are extremely powerful carcinogens (acquired genetic syndromes with high penetrance) while related HPV types are not. In the HPV Methylation Project, we are exploring the epigenetic changes in HPV and host genes in relationship to risk of HPV persistence, progression to CIN3, and invasion.The Persistence and Progression (PaP) cohort is a collaboration with Kaiser Permanente Northern California. More than 40,000 women with dual testing with positive HPV DNA assays and cytology are being followed for outcome. This is the main source of specimens for our studies of HPV genome, epigenetics, and microbiome.The New Mexico Pap Registry is a collaboration with Dr. Cosette Wheeler at U. New Mexico, consisting of a statewide surveillance of cytology and histology outcomes. In a subset, HPV testing is available. The goal eventually is to monitor the impact of HPV vaccination on cervical screening.HPV Cervical Cancer Risk Prediction. This study involves translation of what we have learned about HPV and cervical carcinogenesis into clinical guidelines, particularly via risk prediction models. The main source of data is Kaiser Permanente Northern California, with its decade-long experience with HPV and Pap cotesting.Of note, these studies are intrinsically related to HIV as well. Cervical cancer is an AIDS-defining condition, and there are many links between HIV and HPV. HPV prevalence is profoundly increased in HIV-immunosuppressed women, and our analyses take into account HIV status. The impact of HIV on HPV might be HPV type-specific, giving clues to type-specific immune responses. On the other hand, treatment for cervical cancer and its precursor lesions is destructive and may increase risk of HIV transmission in the healing period if sexual intercourse with an infected partner occurs; this is of great importance to possible HPV screen-and-treat strategies in low-resource regions especially sub-Saharan Africa (GAVI countries).This research project is human population based, and both etiologic and translational.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIACP010206-09
Application #
9770286
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
9
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Cancer Epidemiology and Genetics
Department
Type
DUNS #
City
State
Country
Zip Code
Clarke, Megan A; Fetterman, Barbara; Cheung, Li C et al. (2018) Epidemiologic Evidence That Excess Body Weight Increases Risk of Cervical Cancer by Decreased Detection of Precancer. J Clin Oncol 36:1184-1191
Silver, Michelle I; Gage, Julia C; Schiffman, Mark et al. (2018) Clinical Outcomes after Conservative Management of Cervical Intraepithelial Neoplasia Grade 2 (CIN2) in Women Ages 21-39 Years. Cancer Prev Res (Phila) 11:165-170
Schiffman, Mark; Wentzensen, Nicolas (2017) Effective use of human papillomavirus testing for cervical cancer screening requires extended intervals to target persistent infections and precancerous lesions. Prev Med 105:378-380
Schiffman, Mark (2017) Cervical cancer screening: Epidemiology as the necessary but not sufficient basis of public health practice. Prev Med 98:3-4
Schiffman, Mark; Yu, Kai; Zuna, Rosemary et al. (2017) Proof-of-principle study of a novel cervical screening and triage strategy: Computer-analyzed cytology to decide which HPV-positive women are likely to have ?CIN2. Int J Cancer 140:718-725
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Silver, Michelle I; Schiffman, Mark; Fetterman, Barbara et al. (2016) The population impact of human papillomavirus/cytology cervical cotesting at 3-year intervals: Reduced cervical cancer risk and decreased yield of precancer per screen. Cancer 122:3682-3686
Schiffman, Mark; Wentzensen, Nicolas (2016) A Suggested Approach to Simplify and Improve Cervical Screening in the United States. J Low Genit Tract Dis 20:1-7
Gage, Julia C; Hunt, William C; Schiffman, Mark et al. (2016) Similar Risk Patterns After Cervical Screening in Two Large U.S. Populations: Implications for Clinical Guidelines. Obstet Gynecol 128:1248-1257
Zhao, Fang-Hui; Hu, Shang-Ying; Zhang, Qian et al. (2016) Risk assessment to guide cervical screening strategies in a large Chinese population. Int J Cancer 138:2639-47

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