Project Summary A diagnosis of Head and neck squamous cell carcinoma (HNSCC) includes many cancer subtypes. We will focus on the oral cavity squamous cell carcinoma (OSCC) subtype on the proposed project. OSCC is the 11th most common malignancy in the world. Despite advances in treatments, the 5-year survival rates for OSCC have not improved for the past 25 years. OSCC is a very aggressive tumor, and the majority of patients displays a locoregionally advanced disease at diagnosis, for which multimodality therapy is required. Tumor invasion, lymph node metastasis and high rates of locoregional recurrence, besides development of second primary tumors, are the leading causes of death for OSCC patients. At least 50% of patients with locally advanced OSCC develop locoregional or distant relapses, which usually occur within the first 2 years of treatment completion. Treatment in high-quality hospitals is associated with improved survival for patients with OSCC. However, African American patients are less likely to be treated in high-quality hospitals compared with non-Latino white patients in US, as well as poor patients worldwide. Most HNSCC cases worldwide are detected at later stage of cancer because screening is not routinely conducted, leading to disparities at diagnosis based on rurality, race, and gender, which can be reduced by targeted screening. OSCC is one of the tumors in which the most glaring disparities exist worldwide. The dramatic disparity in incidence rates between high- and low-income countries is due primarily to differential access to effective screening and pre- cancer, or preventive, treatment. Similar disparities also exist within developed countries like the US where the burden of OSCC is highest in low-income populations. OSCC molecular screening should be included in dental visits for adults because early detection of OSCC is associated with better survival. The development of OSCC is a multistep process requiring the accumulation of multiple DNA alterations, influenced by a patient's genetic predisposition as well as by environmental influences, including tobacco, alcohol, chronic inflammation, and infection with Human Papilloma Virus. DNA alterations consist of two major types: alterations in tumor suppressor genes, which promote tumor development when inactivated; and alterations in oncogenes, which promote tumor development when activated. Tumor suppressor genes can be inactivated through genetic events or by epigenetic modifications such as DNA methylation. Gene silencing by aberrant DNA methylation is an important epigenetic event in cancer development and progression, which has great potential as a biomarker for early diagnosis, tumor molecular subtyping, prognosis, monitoring, and therapy. In this Fast Track SBIR project, we propose to demonstrate the feasibility for the commercialization of a precision DNA methylation test, the OralMethDx Test, to stratify patients at high risk of OSCC. Our business plan is to evaluate the performance of the OralMethDx Test for two separate indications: A saliva test for risk stratification in screening and early detection; and tissue biopsy test for diagnosis and prognostication.

Narrative We propose to examine the feasibility for the commercialization of the OralMethDX Test, a rapid saliva test for oral cavity squamous cell carcinoma (OSCC) that enables the identification of patients with early-stage lesions and advanced disease. A highly sensitive and specific precision screening test will reduce oral cancer disparities in low-income populations worldwide.