Human papillomavirus (HPV) associated head and neck cancer is a growing public health concern. These patients commonly present at a younger age and with more advanced stage disease than patients with traditional tobacco and alcohol associated head and neck squamous cell carcinoma (HNSCC). Paradoxically, these HPV-associated tumors show notably improved survival outcomes. Mechanisms underlying these improved outcomes remain unclear. The work proposed in this Pathways to Independence Award has two primary goals: 1) to facilitate career development of the principal investigator (PI) and to help establish his independence to lead a research program investigating radiation response in virally associated cancers;and, 2) to understand how HPV-associated HNSCC differs from traditional HNSCC in response to radiation and chemotherapy. During the mentored phase of research, the PI will obtain additional training in molecular virology, human papillomavirus biology, and mouse models of cancer. The research conducted during the mentored phase will examine why HPV-associated HNSCC are more sensitive than traditional HNSCC to radiation and chemotherapy and to examine the ability of epidermal growth factor receptor (EGFR) inhibitors to sensitize HPV-associated head and neck cancer to radiation despite low levels of EGFR expression. During the independent phase, research will examine the impact of HPV viral proteins on EGFR inhibitor-mediated radiosensitization and the impact of EGFR loss on radiosensitization strategies. These studies will provide new clues regarding mechanisms of increased sensitivity to radiation and chemotherapy and may identify important new targets for therapy development to further improve outcome for patients with both HPV-associated and non-HPV-associated head and neck cancer.

Public Health Relevance

Head and neck squamous cell carcinomas associated with human papillomavirus (HPV) infection are rapidly increasing in global incidence, often present at an advanced stage, are commonly treated with radiation and chemotherapy, and generally show an improved prognosis;nevertheless, selection of optimal therapy remains ill defined. This proposal investigates molecular mechanisms of treatment response with a goal to identify novel means of radiosensitization, the relationship between epidermal growth factor receptor (EGFR) signaling and radiosensitivity, and potential novel mechanisms of radiosensitization. The ultimate objective is to design rationale combinations of radiation and chemotherapy to further improve outcome and/or decrease treatment toxicity.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Career Transition Award (K99)
Project #
5K99CA160639-02
Application #
8296481
Study Section
Subcommittee G - Education (NCI)
Program Officer
Schmidt, Michael K
Project Start
2011-07-05
Project End
2013-02-28
Budget Start
2012-07-01
Budget End
2013-02-28
Support Year
2
Fiscal Year
2012
Total Cost
$149,040
Indirect Cost
$11,040
Name
University of Wisconsin Madison
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Rosenberg, Stephen A; Francis, David M; Hullet, Craig R et al. (2017) Online patient information from radiation oncology departments is too complex for the general population. Pract Radiat Oncol 7:57-62
Prabakaran, Prashanth J; Javaid, Amal M; Swick, Adam D et al. (2017) Radiosensitization of Adenoid Cystic Carcinoma with MDM2 Inhibition. Clin Cancer Res 23:6044-6053
Wojcieszynski, Andrzej P; Olson, Anna K; Rong, Yi et al. (2016) Acute Toxicity From Breast Cancer Radiation Using Helical Tomotherapy With a Simultaneous Integrated Boost. Technol Cancer Res Treat 15:257-65
Rosenberg, Stephen A; Francis, David; Hullett, Craig R et al. (2016) Readability of Online Patient Educational Resources Found on NCI-Designated Cancer Center Web Sites. J Natl Compr Canc Netw 14:735-40
Liang, Evan; Brower, Jeffrey V; Rice, Stephanie R et al. (2015) Merkel Cell Carcinoma Analysis of Outcomes: A 30-Year Experience. PLoS One 10:e0129476
Stein, Andrew P; Saha, Sandeep; Kraninger, Jennifer L et al. (2015) Prevalence of Human Papillomavirus in Oropharyngeal Cancer: A Systematic Review. Cancer J 21:138-46
Morris, Zachary S; Weichert, Jamey P; Saker, Jarob et al. (2015) Therapeutic combination of radiolabeled CLR1404 with external beam radiation in head and neck cancer model systems. Radiother Oncol 116:504-9
Brand, Toni M; Iida, Mari; Stein, Andrew P et al. (2015) AXL Is a Logical Molecular Target in Head and Neck Squamous Cell Carcinoma. Clin Cancer Res 21:2601-12
Stein, Andrew P; Saha, Sandeep; Liu, Cheng Z et al. (2014) Influence of handling conditions on the establishment and propagation of head and neck cancer patient derived xenografts. PLoS One 9:e100995
Swick, Adam; Kimple, Randall J (2014) Wetting the whistle: neurotropic factor improves salivary function. J Clin Invest 124:3282-4

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