Project Summary/Abstract The goal of the EDRN Southwest Clinical Validation Center for Head and Neck Cancer is to improve oropharyngeal cancer screening through the rigorous validation of salivary biomarkers. The scientific approach of our Center is based on several fundamental principles. First, that human papillomaviral (HPV) infection and persistence induces carcinogenesis in the oropharynx over decades, generating well-documented circulating and salivary viral nucleic acid and serologic biomarkers. These biomarkers have not yet been tested in rigorous, prospective studies with centralized CLIA/CAP biomarker validation. Second, the low incidence requires that effective screening paradigms for oropharyngeal cancers (OPC) use novel systems for large-scale prospective studies using self-collection sampling, digital enrollment, and distributive systems to enable enrollment in underserved communities. Third, that the clinical management of positive biomarkers be rigorously addressed. Our proposal builds on our extensive experiences with cancer biomarker development, verification, validation, innovative clinical study management, and expertise in HPV oropharyngeal cancer screening. Our previous results on HPV serologic biomarkers have been confirmed in blinded phase 2 multicenter validation studies. Our results have shown that multiplexed panels of IgG antibodies for HPV16 are required for adequate predictive value. Our Meso Scale Diagnostics, LLC. (MSD®) team has fielded over 3,000 instruments worldwide, and over 700 commercially available biomarker assay kits. Their expertise at serologic assay development led to one of their V-PLEX® serology panels being selected by Operation Warp Speed as the basis of its standard binding assays for immunogenicity assessments in all funded Phase III clinical trials of COVID vaccines. We will use the MSD MULTI-ARRAY® platform to migrate the HPV serologic markers for target clinical applications in saliva. This represents an ongoing collaboration with experts in large-scale self-collection salivary biomarker screening at Arizona State University, experts on head and neck cancer screening at Baylor University Medical Center, and AT Still University (ATSU) School of Dentistry and Oral Health. We will generate high-quality well-characterized samples to validate circulating and salivary biomarkers to enhance oropharyngeal cancer screening. Adhering to the principles of PRoBE design, we will perform Phase 2 validation of HPV serology and nucleic acid testing with cancer patient and control sera and saliva, followed by developing and testing the methodology needed to conduct a prospective Phase 4 salivary screening study. We will provide a resource for expertise and clinical repository for the rigorous validation of salivary and circulating biomarkers for cancer screening.

Project Narrative We will rigorously evaluate existing immune and viral biomarkers in blood and saliva to develop clinical screening paradigms for the early detection of HPV-associated head and neck cancers.