Squamous cell carcinoma of the oral cavity and oropharynx (OSCC) is a substantial global health burden, with an estimate of 529,000 new cases and over 292,000 deaths in 2012. OSCC can be further subclassified into entities with a different prognosis. For example, patients with human papillomavirus (HPV)-positive oropharyngeal cancer (OPC) tend to have better survival than those with HPV-negative OPC. However, prognostication for oral cavity cancer, which comprises the majority of OSCC and is mostly HPV-negative, is largely based on clinical staging, and molecular markers that could be used in clinical practice have not been identified. There is an urgent need to develop better prognostic markers for personalized clinical management of these patients. Our long-term goal is to develop simple, reliable, and cost-effective gene expression signatures to guide the management of OSCC patients. In our prior work (the Oralchip study, 5 R01 CA095419, PI: Chu Chen), we have identified a prognostic gene expression signature in tumor tissue that showed a greater ability than tumor stage to predict OSCC-specific survival for patients with HPV-negative OSCC, irrespective of types of treatment. We validated this signature using an independent set of patients with oral cavity cancer from the MD Anderson Cancer Center. This was the first demonstration of a gene expression signature that provides prognostic information beyond AJCC stage for oral cavity cancer patients.
The specific aims of the proposed study are to leverage the available diagnostic tumor blocks, demographic and clinical information and survival outcomes of oral cavity cancer patients from five head and neck cancer studies (Fred Hutchinson Cancer Research Center/Univ. of Washington; Univ. of Calgary; Univ. of Michigan; Univ. of Utah; and the International Agency of Research on Cancer) to 1) test the hypothesis that the prognostic ability of our 9-gene signature for HPV-negative OSCC patients, that was developed and validated using snap frozen fresh tumor tissue and Affymetrix gene expression arrays, can be transported to formalin-fixed paraffin embedded (FFPE) hospital tumor blocks of HPV-negative, p16-negative oral cavity cancer patients and NanoString nCounter technology, and to build prediction models for overall and oral cavity cancer-specific survival; 2) validate th prediction models using independent cohorts of HPV-negative, p16-negative oral cavity cancer patients; and 3) evaluate whether the ability of the gene signature to predict survival, overall an OSCC-specific, would be influenced by treatment modalities (surgery alone; surgery + radiation; and surgery + radiation + chemotherapy) that collectively were administered to ~90% of the study participants. This study is significant and novel because it has the potential to deliver, fr the first time, a rapid, inexpensive, and reliable multi-marker assay that can be run on hospital diagnostic FFPE samples, routinely prepared by the hospital at the time of surgery, to improve survival prediction of HPV-negative oral cavity cancer patients, and thus lead to improved clinical care of patients with this often lethal disease.
Oral cancer is a substantial global health burden, with an estimated 529,000 new cases and 292,000 deaths occurred in 2012. The results of this study have the potential to create, for the first time, a rapid, reliable, and cost-effective formalin-fied, paraffin-embedded tumor based assay to improve the prediction of survival of human papillomavirus-negative oral cavity cancer patients and help physicians and patients to make timely, personalized treatment choices.
