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.
Public Health Relevance Statement: 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.
Project Terms: 21+ years old; Adult Human; adulthood; Adult; Alcohol Drinking; EtOH drinking; EtOH use; alcohol ingestion; alcohol intake; alcohol product use; alcohol use; alcoholic beverage consumption; alcoholic drink intake; ethanol consumption; ethanol drinking; ethanol ingestion; ethanol intake; ethanol product use; ethanol use; Alcohol consumption; Alcohol Chemical Class; Alcohols; Anatomic Sites; Anatomic structures; Anatomy; Biopsy; Black race; Black; Malignant Neoplasms; Cancers; Malignant Tumor; malignancy; neoplasm/cancer; Cause of Death; Classification; Systematics; Combined Modality Therapy; Multimodal Therapy; Multimodal Treatment; combination therapy; combined modality treatment; combined treatment; multi-modal therapy; multi-modal treatment; Diagnosis; Oral Diagnosis; DNA; Deoxyribonucleic Acid; Exhibits; Gene Expression; Genes; Recording of previous events; History; histories; Hospitals; Incidence; Infection; Human Papillomavirus; HPV; Human Papilloma Virus; Infectious Human Wart Virus; wart virus; Inflammation; Low Income Population; Low income group; low income individual; low income people; Methylation; Mutation; Genetic Alteration; Genetic Change; Genetic defect; genome mutation; Oncogenes; Cancer Genes; Cancer-Promoting Gene; Transforming Genes; Oral Stage; Patients; Promoter Regions; Promotor Regions; genetic promoter element; genetic promoter sequence; promoter sequence; Publishing; Race; Races; racial; racial background; racial origin; Recommendation; Recurrence; Recurrent; Research; Risk; Saliva; Specificity; Survival Analysis; Survival Analyses; Survival Rate; Technology; Testing; Tissues; Body Tissues; Tobacco; United States; Virus Diseases; Viral Diseases; viral infection; virus infection; virus-induced disease; Gender; Tumor Suppressor Genes; Anti-Oncogenes; Antioncogenes; Cancer Suppressor Genes; Emerogenes; Onco-Suppressor Genes; Oncogenes-Tumor Suppressors; Recessive Oncogenes; Tumor Suppressing Genes; oncosuppressor gene; TP53 gene; Antioncogene Protein p53; Cellular Tumor Antigen P53; Oncoprotein p53; P53; Phosphoprotein P53; Phosphoprotein pp53; Protein TP53; TP53; TRP53; Tumor Protein p53; Tumor Protein p53 Gene; p53 Antigen; p53 Genes; p53 Tumor Suppressor; protein p53; Afro American; Afroamerican; African American; Businesses; Latino; promotor; promoter; Malignant Oral Cavity Neoplasm; Malignant Oral Cavity Tumor; Malignant Oral Neoplasm; Mouth Cancer; Oral Cancer; malignant mouth tumor; oral cavity cancer; malignant mouth neoplasm; rural location; rural region; rural area; improved; Chronic; Clinical; Link; Evaluation; prognostic; Dental; Industrialized Countries; Industrialized Nations; developed country; developed nation; developed nations; Developed Countries; Genetic; Genetic Predisposition to Disease; Genetic Predisposition; Genetic Susceptibility; Genetic propensity; Inherited Predisposition; Inherited Susceptibility; genetic etiology; genetic mechanism of disease; genetic vulnerability; genetically predisposed; Diagnostic; DNA Methylation; Frequencies; Event; Salivary; Distant; Location; Operative Surgical Procedures; Operative Procedures; Surgical; Surgical Interventions; Surgical Procedure; surgery; Visit; mouth squamous cell carcinoma; Oral Cavity Squamous Cell Carcinoma; Oral squamous cell carcinoma; mouth SCC; oral cavity SCC; oral squamous cancer; oral squamous carcinoma; Early Diagnosis; early detection; Performance; diagnostic accuracy; Accuracy of Diagnosis; Gene Silencing; Gene Inactivation; transcriptional silencing; Primary Neoplasm; Primary Tumor; advanced disease; advanced illness; Metastatic Neoplasm to Lymph Nodes; Metastasis to Lymph Nodes; Metastatic Tumor to Lymph Nodes; lymph node metastasis; Genomics; HNSCC; Head and Neck Carcinoma; SCCHN; head and neck squamous carcinoma; head and neck squamous cell cancer; Head and Neck Squamous Cell Carcinoma; Tumor Invasion; Tumor Cell Invasion; preventing; prevent; Causality; causation; disease causation; Etiology; Lesion by Stage; PAX5 gene; PAX5; Preventive; Aberrant DNA Methylation; DNA Sequence Alteration; DNA Alteration; DNA mutation; Genetic mutation; Sequence Alteration; genomic alteration; Data; Detection; Hypermethylation; premalignant; precancer; precancerous; Prognostic Marker; prognostic biomarker; Cancer Burden; National Cancer Burden; Epigenetic Process; Epigenetic; Epigenetic Change; Epigenetic Mechanism; epigenetically; Newly Diagnosed; Small Business Innovation Research Grant; SBIR; Small Business Innovation Research; Tumor Promotion; Monitor; Molecular; Process; Modification; Development; developmental; tobacco control; exposure to tobacco; tobacco exposure; epigenomics; saliva assay; saliva based assay; saliva based test; saliva test; salivary test; salivary assay; cost; Outcome; cancer disparity; cancer-related health disparity; disparity in cancer; cancer health disparity; commercialization; tumor; high risk; bio-markers; biologic marker; biomarker; Biological Markers; social health determinants; TCGA; The Cancer Genome Atlas; screenings; screening; methylome; precision screening; personalized screening; methylation marker; methylation biomarker; methylation testing; LMIC; low and middle-income countries; stratified patient; patient stratification; early biomarkers; early detection markers; early detection biomarkers; expression subtypes; molecular sub-types; molecular subsets; molecular subtypes; cancer sub-types; cancer subtypes; differences in health; health difference; low income country; stratify risk; risk stratification; rurality; rural patients; gene testing; gene-based testing; genetic testing; salivary sample; saliva sample; Prognosis; prognostication; Resource-limited setting; Low-resource area; Low-resource community; Low-resource environment; Low-resource region; Low-resource setting; Resource-constrained area; Resource-constrained community; Resource-constrained environment; Resource-constrained region; Resource-constrained setting; Resource-limited area; Resource-limited community; Resource-limited environment; Resource-limited region; Resource-poor area; Resource-poor community; Resource-poor environment; Resource-poor region; Resource-poor setting; African American population; African American group; African American individual; African American people; African Americans; Disparity; Disparities
