Project 1

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PROJECT SUMMARY Squamous cell head and neck cancer (SCHNC) results in extensive physical disfigurement, and leads to ~40% 5-year mortality; thus its prevention is extremely important. Blacks and people with low socioeconomic status (SES) have a high burden of SCHNC. We hypothesize that the oral microbiota contribute to the racial and socioeconomic disparities in SCHNC. Oral bacteria and fungi can cause epithelial cell DNA damage by carcinogen metabolism, and some of these somatic mutations may be critical for SCHNC carcinogenesis. Bacteria and fungi may also promote carcinogenesis through immunogenic stimulus for innate immune system response via pattern recognition receptors, leading to immune cell recruitment and an altered tumor immune microenvironment. Thus, a microbial role in SCHNC development and the shaping of the tumor mutational and immune microenvironment is of great potential importance in the pathogenesis of SCHNC. Our preliminary data show that Blacks and individuals with low socioeconomic status exhibit lower overall oral microbiome diversity, particularly characterized by lower abundance of bacteria Corynebacterium and Kingella; we had previously reported that low abundance of these two bacteria is also associated with increased risk of SCHNC development. Our work further points to involvement of oral bacteria in carcinogen metabolism, with potential impact on tumor mutational load and immune infiltration. While this preliminary data supports our hypothesis, no studies have examined the comprehensive relationship between the oral microbiome, tumor microenvironment, and SCHNC in racial and socioeconomic minority populations. Our overall goal is to generate important biologic insights about oral microbial factors that underlie racial and socioeconomic disparities in SCHNC development. In this research, we expect to identify specific oral microbiota contributing to these disparities and to identify the tumor microbiota that influences host tumor mutation burden and the tumor immune microenvironment. This project will help to achieve SCHNC health equity by generating novel information from diverse population groups about the role of the oral microbiome in SCHNC development and pathogenesis. Knowledge gained may improve our ability to identify people at high risk of SCHNC, particularly in underserved minority groups. The new information may further lead to novel prevention and therapeutics approaches that exploit microbially-driven immune responses in SCHNC.