Squamous cell carcinoma of the oropharynx (SCCOP) is characterized by local tumor aggressiveness requiring morbid local-regional therapies with poor survival and high recurrence rates. Despite declining smoking prevalence, the incidence of SCCOP is increasing, particularly in young adults. These trends may be due to the rising prevalence of oncogenic human papillomavirus (HPV) in the population. HPV-positive [(HPV+)] SCCOP is a distinct epidemiologic, clinical, and molecular disease with potentially unique clinical behavior and treatment responses. Identification of those needing treatment intensification and those able to benefit from reduction of treatment intensity is critical to more effective and less morbid treatment. Oncogenic subtypes of HPV are critical etiologic factors in a distinct subset of head and neck cancers, chiefly SCCOP. Inflammatory response miRNAs which control the HPV clearance and escape of immune surveillance may contribute to HPV(+) tumors and related outcomes of SCCOP. In addition, miRNAs in human serum hold a great potential for serum-based biomarker research. Thus, serum expression profiles of inflammatory response miRNAs before treatment may affect tumor HPV status and related outcomes of SCCOP patients; and exploitation of such associations may help develop clinically relevant non-tumor-based biomarkers for HPV- associated SCCOP patients. In this study, the study subjects will be 600 patients with incident SCCOP identified from an existing molecular epidemiologic study of squamous cell carcinoma of the head and neck.
The specific aims for this R03 project are:
Aim 1 : To assess if serum expression profiles of selected inflammatory/immune response miRNAs before treatment are markers of tumor HPV status among the 600 SCCOP patients. We will determine serum expression of those selected miRNAs before treatment by using the miScript miRNA PCR arrays method and Aim 2: To determine if certain serum expression profiles of above miRNAs before treatment as blood-based and non-tumor predictors of clinical outcomes of HPV(+) SCCOP patients including disease-specific survival, disease-free survival, and overall survival among 600 SCCOP patients treated and followed at U.T. MDACC. By knowing the tumor HPV status and identifying novel prognostic biomarkers of HPV-associated SCCOP patients, physicians can effectively tailor treatment, screening, and follow-up strategies for an improved survival and a better quality of life as well as greatly enhanced secondary cancer prevention.

Public Health Relevance

Despite declining smoking rates in the U.S, the incidence of squamous cell carcinoma of the oropharynx (SCCOP) has been stagnant overall and increasing in young adults, possibly attributed to an increase in HPV prevalence, and if true, our public health SCCOP prevention paradigm will need to expand beyond tobacco and alcohol control. Identification of biomarkers for HPV status would be useful to identify those individuals who are susceptible to HPV infection, to refine the prognostication of HPV associated SCCOP, and ultimately to improve prevention efforts for SCCOP and potentially other HPV-associated diseases. This has obvious implications for molecular mechanistic knowledge, preventive medicine, potentially better individualized treatment of SCCOP with resulting better survival and quality of life.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Small Research Grants (R03)
Project #
5R03CA186261-02
Application #
9017966
Study Section
Special Emphasis Panel (ZCA1)
Program Officer
Verma, Mukesh
Project Start
2015-04-01
Project End
2017-03-31
Budget Start
2016-04-01
Budget End
2017-03-31
Support Year
2
Fiscal Year
2016
Total Cost
Indirect Cost
Name
University of Texas MD Anderson Cancer Center
Department
Surgery
Type
Hospitals
DUNS #
800772139
City
Houston
State
TX
Country
United States
Zip Code
77030
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Tao, Ye; Sturgis, Erich M; Huang, Zhigang et al. (2018) TGF?1 Genetic Variants Predict Clinical Outcomes of HPV-Positive Oropharyngeal Cancer Patients after Definitive Radiotherapy. Clin Cancer Res 24:2225-2233
Tao, Ye; Sturgis, Erich M; Huang, Zhigang et al. (2018) A TGF-?1 genetic variant at the miRNA187 binding site significantly modifies risk of HPV16-associated oropharyngeal cancer. Int J Cancer 143:1327-1334
Lu, Zhongming; Sturgis, Erich M; Zhu, Lijun et al. (2018) Mouse double minute 4 variants modify susceptibility to risk of recurrence in patients with squamous cell carcinoma of the oropharynx. Mol Carcinog 57:361-369
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Lu, Zhongming; Zhang, Hua; Tao, Ye et al. (2017) MDM4 genetic variants predict HPV16-positive tumors of patients with squamous cell carcinoma of the oropharynx. Oncotarget 8:86710-86717
Zhu, Lijun; Sturgis, Erich M; Lu, Zhongming et al. (2017) Association between miRNA-binding site polymorphisms in double-strand break repair genes and risk of recurrence in patients with squamous cell carcinomas of the non-oropharynx. Carcinogenesis 38:432-438
Zhang, Yang; Sturgis, Erich M; Li, Yuncheng et al. (2017) Modifying effect of mouse double minute-2 promoter variants on risk of recurrence for patients with squamous cell carcinoma of oropharynx. Sci Rep 7:39765
Chen, Xingming; Sturgis, Erich M; Wang, Chengyuan et al. (2016) Significance of microRNA-related variants in susceptibility to recurrence of oropharyngeal cancer patients after definitive radiotherapy. Oncotarget 7:35015-25

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