A subset of mucosotropic human papillomaviruses (HPVs) are the principle causative agent for anogenital cancers, most notably cervical cancer. In these cancers the HPV genome is present and a subset of viral genes with oncogenic potential is expressed. These same 'high risk"""""""" (HR) HPVs now have been found in approximately 20% of human head and neck squamous cell carcinomas (HNSCC), and of these most frequently in tonsillar cancers. Notably, HPV16, the HR-HPV most commonly found in cervical cancer is the HPV most commonly found in HNSCC. Molecular analyses indicate that HPV-positive HNSCC differ from HPV-negative HNSCC, for which tobacco smoke and alcohol are the main etiological agents. Immunocompromised patients including HIV-infected individuals and organ transplant patients undergoing immunosuppressive therapy are at increased risk of HPV infections and resultant lesions in the anogenital tract and oral cavity. We have recently established the first mouse model for HPV-associated oral carcinogenesis. In this grant application, we propose studies to fully characterize this mouse model in comparison to HPV-associated human HNSCC, and to use this mouse model to assess the contributions and define the mechanisms of action of HPV16 oncogenes in oral carcinogenesis. ? ?

National Institute of Health (NIH)
National Institute of Dental & Craniofacial Research (NIDCR)
Research Project (R01)
Project #
Application #
Study Section
AIDS-associated Opportunistic Infections and Cancer Study Section (AOIC)
Program Officer
Shirazi, Yasaman
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Wisconsin Madison
Internal Medicine/Medicine
Schools of Medicine
United States
Zip Code
Kimple, Randall J; Harari, Paul M; Torres, Alexandra D et al. (2013) Development and characterization of HPV-positive and HPV-negative head and neck squamous cell carcinoma tumorgrafts. Clin Cancer Res 19:855-64
Kimple, Randall J; Smith, Molly A; Blitzer, Grace C et al. (2013) Enhanced radiation sensitivity in HPV-positive head and neck cancer. Cancer Res 73:4791-800
Rahimpour, Azad; Mattarollo, Stephen R; Yong, Michelle et al. (2012) ýýýý T cells augment rejection of skin grafts by enhancing cross-priming of CD8 T cells to skin-derived antigen. J Invest Dermatol 132:1656-64
Shin, Myeong-Kyun; Pitot, Henry C; Lambert, Paul F (2012) Pocket proteins suppress head and neck cancer. Cancer Res 72:1280-9
Newton, Michael A; He, Qiuling; Kendziorski, Christina (2012) A model-based analysis to infer the functional content of a gene list. Stat Appl Genet Mol Biol 11:
Thomas, Marie K; Pitot, Henry C; Liem, Amy et al. (2011) Dominant role of HPV16 E7 in anal carcinogenesis. Virology 421:114-8
Park, Jung Wook; Pitot, Henry C; Strati, Katerina et al. (2010) Deficiencies in the Fanconi anemia DNA damage response pathway increase sensitivity to HPV-associated head and neck cancer. Cancer Res 70:9959-68
Jabbar, Sean; Strati, Katerina; Shin, Myeong Kyun et al. (2010) Human papillomavirus type 16 E6 and E7 oncoproteins act synergistically to cause head and neck cancer in mice. Virology 407:60-7
Stelzer, Marie K; Pitot, Henry C; Liem, Amy et al. (2010) Rapamycin inhibits anal carcinogenesis in two preclinical animal models. Cancer Prev Res (Phila) 3:1542-51
Stelzer, Marie K; Pitot, Henry C; Liem, Amy et al. (2010) A mouse model for human anal cancer. Cancer Prev Res (Phila) 3:1534-41

Showing the most recent 10 out of 16 publications