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Grant Details

Grant Number: 5R01CA211939-05 Interpret this number
Primary Investigator: Zevallos, Jose
Organization: Washington University
Project Title: Development of a Four-Class, Molecular Subtyping Diagnostic for HPV-Negative Head and Neck Cancer
Fiscal Year: 2021


Abstract: Head and neck squamous cell carcinoma (HNSCC), including cancers of the oral cavity, pharynx, and larynx, is the sixth most common cancer worldwide worldwide. In the United States, approximately 60,000 new cases of HNSCC and 12,000 deaths are projected for 2015. A growing body of evidence demonstrates increasing incidence of oropharyngeal cancers, including a subset of human papillomavirus (HPV) associated tumors that demonstrate better prognosis. Despite the recent research interest in HPV-positive HNSCC, HPV-negative tobacco-associated cases continue to comprise the vast majority of HNSCC. Particularly in our state of North Carolina, where the population is more racially and socioeconomically diverse and where tobacco use remains high, HPV-negative HNSCC remains a significant public health problem. Oncologic outcomes for HPV-negative HNSCC remain poor and have not improved in the last 50 years, and there is a need to identify novel, personalized diagnostics and treatment strategies for patients with HPV-negative HNSCC. Four intrinsic HNSCC gene expression subtypes (basal (BA), classical (CL), mesenchymal (MS) and atypical (AT)) have been described, and provide an opportunity to inform patient management. These subtypes exhibit distinct differences in cell of origin, tumor drivers, proliferation, prognosis, and host immune response. In this application, we intend to develop and validate a clinic-ready diagnostic for HPV-negative HNSCC that includes both prognostic and predictive applications. While several therapeutic options exist for HNSCC including surgery, radiation therapy, and, chemotherapy, treatment selection remains empiric. With the exception of HPV status in oropharyngeal cancer, the molecular characteristics of individual tumors are generally not taken into account when deciding on treatment. This academic/industry collaboration will provide prognostic information based on biologic gene expression subtypes to guide decision-making for HPV-negative HNSCC, such as application of more aggressive surgery or radiation therapy based on tumor characteristics. We hypothesize that development efforts as described in this application will lead to a clinic-ready subtyping diagnostic, that combined with other mutation and clinical data, will provide both prognostic and predictive applications to guide the management of HNSCC.


Integrative Analysis of miRNAs Identifies Clinically Relevant Epithelial and Stromal Subtypes of Head and Neck Squamous Cell Carcinoma.
Authors: Holt J. , Walter V. , Yin X. , Marron D. , Wilkerson M.D. , Choi H.Y. , Zhao X. , Jo H. , Hayes D.N. , Ko Y.H. .
Source: Clinical cancer research : an official journal of the American Association for Cancer Research, 2021-02-01; 27(3), p. 831-842.
EPub date: 2020-11-04.
PMID: 33148669
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National trends in oropharyngeal cancer incidence and survival within the Veterans Affairs Health Care System.
Authors: Zevallos J.P. , Kramer J.R. , Sandulache V.C. , Massa S.T. , Hartman C.M. , Mazul A.L. , Wahle B.M. , Gerndt S.P. , Sturgis E.M. , Chiao E.Y. .
Source: Head & neck, 2021 01; 43(1), p. 108-115.
EPub date: 2020-09-12.
PMID: 32918302
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Transoral Robotic Surgery and De-escalation of Cancer Treatment.
Authors: Wahle B. , Zevallos J. .
Source: Otolaryngologic clinics of North America, 2020 Dec; 53(6), p. 981-994.
EPub date: 2020-09-08.
PMID: 32917423
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A conditional mouse expressing an activating mutation in NRF2 displays hyperplasia of the upper gastrointestinal tract and decreased white adipose tissue.
Authors: Bowman B.M. , Montgomery S.A. , Schrank T.P. , Simon J.M. , Ptacek T.S. , Tamir T.Y. , Mulvaney K.M. , Weir S.J. , Nguyen T.T. , Murphy R.M. , et al. .
Source: The Journal of pathology, 2020 10; 252(2), p. 125-137.
EPub date: 2020-08-29.
PMID: 32619021
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Gene Expression Subtype Predicts Nodal Metastasis and Survival in Human Papillomavirus-Negative Head and Neck Cancer.
Authors: Zevallos J.P. , Mazul A.L. , Walter V. , Hayes D.N. .
Source: The Laryngoscope, 2019 01; 129(1), p. 154-161.
EPub date: 2018-09-24.
PMID: 30247749
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RNA Oncoimmune Phenotyping of HPV-Positive p16-Positive Oropharyngeal Squamous Cell Carcinomas by Nodal Status.
Authors: Stepp W.H. , Farquhar D. , Sheth S. , Mazul A. , Mamdani M. , Hackman T.G. , Hayes D.N. , Zevallos J.P. .
Source: JAMA otolaryngology-- head & neck surgery, 2018-11-01; 144(11), p. 967-975.
PMID: 29710215
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Decreased overall survival in black patients with HPV-associated oropharyngeal cancer.
Authors: Sheth S. , Farquhar D.R. , Lenze N.R. , Mazul A. , Brennan P. , Anantharaman D. , Abedi-Ardekani B. , Zevallos J.P. , Hayes D.N. , Olshan F. .
Source: American journal of otolaryngology, 2021 Jan - Feb; 42(1), p. 102780.
EPub date: 2020-10-22.
PMID: 33152576
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