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.
The goal of this project is to develop, validate and commercialize a four-class, molecular subtyping diagnostic for HPV-negative head and neck squamous cell carcinoma (HNSCC). Despite significant gains in knowledge of the molecular etiology of non-HPV HNSCC over the past twenty years, little progress has been made in utilizing this information to improve patient outcomes. In fact, survival statistics have not improved for these patients since the 1960?s. Preliminary studies performed by the Hayes laboratory suggest that the integration of HNSCC subtype with additional molecular markers and clinical features may yield molecular models with significantly enhanced prognostic and predictive capabilities. In this project, Dr. Jose Zevallos, in collaboration with the Hayes laboratory and GeneCentric Diagnostics, will develop and commercialize a novel HNSCC subtyping assay. This proposal focuses on the integration of HNSCC subtype with molecular markers and clinical feature data to produce a clinically relevant assay to provide more accurate and precise prognostic and predictive applications for the purpose of guiding patient care.
| Stepp, Wesley H; Farquhar, Douglas; Sheth, Siddharth et al. (2018) RNA Oncoimmune Phenotyping of HPV-Positive p16-Positive Oropharyngeal Squamous Cell Carcinomas by Nodal Status. JAMA Otolaryngol Head Neck Surg 144:967-975 |
