HPV plays an etiologic role in the development of a distinct subset of oral cancers that arise predominantly from the tonsils. HIV-infected individuals are at increased risk for tonsillar cancer. Oral HPV infection is therefore a newly appreciated public health problem. The objective of this proposal is to perform a comprehensive molecular epidemiologic study to determine the prevalence, risk factors, mechanisms of transmission, and natural history of oral human papillomavirus (HPV) infection in HIV-infected individuals and to identify precursor lesions for HPV-associated head and neck squamous cell carcinomas (HPV associated HNSCC). Tonsillar cancers comprise approximately 15-23% of all oral and oropharyngeal cancers. There was a 2-3% increase in tonsillar cancer incidence per year from 1973-1995 in men in the United States. Concurrent HPV and HIV infection may have contributed to this unexplained increase. Preliminary data suggest that the odds of oral and tonsillar infection by a high-risk HPV type are significantly elevated in HIV infected individuals, and that oral HPV infection is associated with sexual behaviors, severity of immunosuppression and the presence of potentially premalignant oral mucosal lesions. A prospective cohort study of 800 HIV-infected men and women with 36 months of semiannual follow-up is proposed to accomplish the following specific aims: (i) to determine the prevalence and type distribution of oral mucosal HPV infection and to characterize host, environmental (tobacco and alcohol) and biological factors (e.g. CD4 count, HIV viral load) associated with oral HPV infection; (ii) to identify specific sexual practices associated with presence of oral HPV infection after adjustment for confounders; (iii) to evaluate the relationship between high-risk HPVs (presence of HPV genomic DNA, viral load, integration) and tonsillar dysplasia and other oral mucosal abnormalities, and (iv) to determine if tobacco use, immunosuppression, and HPV type (low versus high-risk) affect the incidence and/or persistence of oral HPV infection. This proposal has the potential to yield information important for future efforts at primary prevention and early detection of HPV-HNSCC.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE016631-03
Application #
7215690
Study Section
Special Emphasis Panel (ZDE1-PZ (08))
Program Officer
Rodriguez-Chavez, Isaac R
Project Start
2005-05-05
Project End
2009-03-31
Budget Start
2007-04-01
Budget End
2008-03-31
Support Year
3
Fiscal Year
2007
Total Cost
$626,352
Indirect Cost
Name
Johns Hopkins University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Boffetta, Paolo; Hayes, Richard B; Sartori, Samantha et al. (2016) Mouthwash use and cancer of the head and neck: a pooled analysis from the International Head and Neck Cancer Epidemiology Consortium. Eur J Cancer Prev 25:344-8
Wyss, Annah B; Hashibe, Mia; Lee, Yuan-Chin Amy et al. (2016) Smokeless Tobacco Use and the Risk of Head and Neck Cancer: Pooled Analysis of US Studies in the INHANCE Consortium. Am J Epidemiol 184:703-716
Conway, David I; Brenner, Darren R; McMahon, Alex D et al. (2015) Estimating and explaining the effect of education and income on head and neck cancer risk: INHANCE consortium pooled analysis of 31 case-control studies from 27 countries. Int J Cancer 136:1125-39
Beachler, Daniel C; D'Souza, Gypsyamber; Sugar, Elizabeth A et al. (2013) Natural history of anal vs oral HPV infection in HIV-infected men and women. J Infect Dis 208:330-9
Jordan, Richard C; Lingen, Mark W; Perez-Ordonez, Bayardo et al. (2012) Validation of methods for oropharyngeal cancer HPV status determination in US cooperative group trials. Am J Surg Pathol 36:945-54
Gillison, Maura L; Zhang, Qiang; Jordan, Richard et al. (2012) Tobacco smoking and increased risk of death and progression for patients with p16-positive and p16-negative oropharyngeal cancer. J Clin Oncol 30:2102-11
Broutian, Tatevik R; He, Xin; Gillison, Maura L (2011) Automated high throughput DNA isolation for detection of human papillomavirus in oral rinse samples. J Clin Virol 50:270-5
Fakhry, Carole; Rosenthal, Barbara T; Clark, Douglas P et al. (2011) Associations between oral HPV16 infection and cytopathology: evaluation of an oropharyngeal ""pap-test equivalent"" in high-risk populations. Cancer Prev Res (Phila) 4:1378-84
Ang, K Kian; Harris, Jonathan; Wheeler, Richard et al. (2010) Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med 363:24-35
D'Souza, Gypsyamber; Zhang, Hao H; D'Souza, Warren D et al. (2010) Moderate predictive value of demographic and behavioral characteristics for a diagnosis of HPV16-positive and HPV16-negative head and neck cancer. Oral Oncol 46:100-4

Showing the most recent 10 out of 18 publications