Head and neck squamous cell carcinoma carries a high mortality rate despite advances in chemotherapy and radiation therapies. This is due mainly to the highly heterogeneous nature of the disease, both morphologically and genetically. A current shortcoming in the diagnosis, prognosis, and treatment of HNSCC is a lack of methods that adequately address the complexity and diversity of the disease. A major objective of the proposed research is to develop a detailed molecular fingerprint of HNSCC tumor tissues that is linked to clinical information. Diagnostic and prognostic marker systems based on single parameters have generally proven inadequate. Thus, multiparametric methods, which rely on many pieces of information, are ideally suited to the grouping of tumor subtypes and the identification of specific patterns of disease progression and clinical outcomes. Our goal is to accomplish a multivariable comprehensive genome-wide molecular blueprint of HNSCC integrated with clinical risk factors in order to refine patient diagnosis and prognosis to aid in the clinical management of patients at the earliest disease stages. We will interrogate an evidence-based panel of gene loci implicated in head and neck cancer, many of which are distributed along critical pathways utilized by HNSCC cells. The molecular targets to be investigated using a novel assay will be done in an epidemiologically well-characterized cohort of 1000 primary HNSCC derived from a large, multi-ethnic, primary care patient population diagnosed by surgical biopsies in the Henry Ford Health System from 1986-2003, and followed from 5-23 years. This approach should yield a validated multivariable genetic blueprint for diagnosis and prognosis analogous to or even more powerful than TNM-staging, permitting more accurate grouping of tumor subtypes, more accurate distinction of prognostic groups, and better prediction of effective treatment strategies.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE015990-03
Application #
7054761
Study Section
Special Emphasis Panel (ZDE1-PZ (15))
Program Officer
Shirazi, Yasaman
Project Start
2004-08-01
Project End
2009-05-31
Budget Start
2006-06-01
Budget End
2007-05-31
Support Year
3
Fiscal Year
2006
Total Cost
$281,232
Indirect Cost
Name
Henry Ford Health System
Department
Otolaryngology
Type
Schools of Medicine
DUNS #
073134603
City
Detroit
State
MI
Country
United States
Zip Code
48202
Chen, Kang Mei; Stephen, Josena K; Havard, Shaleta et al. (2015) IGSF4 methylation as an independent marker of human papillomavirus-positive oropharyngeal squamous cell carcinoma. JAMA Otolaryngol Head Neck Surg 141:257-63
Worsham, Maria J; Stephen, Josena K; Chen, Kang Mei et al. (2014) Delineating an epigenetic continuum in head and neck cancer. Cancer Lett 342:178-84
Stephen, Josena K; Divine, George; Chen, Kang Mei et al. (2013) Significance of p16 in Site-specific HPV Positive and HPV Negative Head and Neck Squamous Cell Carcinoma. Cancer Clin Oncol 2:51-61
Worsham, Maria J; Stephen, Josena K; Chen, Kang Mei et al. (2013) Improved survival with HPV among African Americans with oropharyngeal cancer. Clin Cancer Res 19:2486-92
Chen, Kang Mei; Stephen, Josena K; Ghanem, Tamer et al. (2013) Human papilloma virus prevalence in a multiethnic screening population. Otolaryngol Head Neck Surg 148:436-42
Worsham, Maria J; Chen, Kang Mei; Ghanem, Tamer et al. (2013) Epigenetic modulation of signal transduction pathways in HPV-associated HNSCC. Otolaryngol Head Neck Surg 149:409-16
Worsham, Maria J; Stephen, Josena K; Lu, Mei et al. (2012) Disparate molecular, histopathology, and clinical factors in head and neck squamous cell carcinoma racial groups. Otolaryngol Head Neck Surg 147:281-8
Worsham, Maria J; Lu, Mei; Chen, Kang Mei et al. (2012) Malignant and nonmalignant gene signatures in squamous head and neck cancer. J Oncol 2012:752860
Stephen, Josena K; Chen, Kang Mei; Havard, Shaleta et al. (2012) Promoter methylation in head and neck tumorigenesis. Methods Mol Biol 863:187-206
Stephen, Josena K; Chen, Kang Mei; Shah, Veena et al. (2012) Human papillomavirus outcomes in an access-to-care laryngeal cancer cohort. Otolaryngol Head Neck Surg 146:730-8

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