Oral Microbial Ecology, NK-Cell Surveillance, and the Inverse Association Between Dental Caries and Head and Neck Cancer: A Hypothesis

Hypothesis paper.An inverse association between dental caries and head and neck squamous cell carcinoma has been reported, although this observation does not establish that dental caries protects against cancer. This paper proposes that the association may reflect differences in oral microbial ecology and host immune regulation rather than caries itself. We hypothesize that caries-associated microbial communities may influence Th1-type immune responses, inflammatory cytokine signaling, and natural killer (NK) cell-mediated tumor immune surveillance. In contrast, periodontal dysbiosis, including Fusobacterium nucleatum and other inflammation-associated oral bacteria, may promote chronic inflammatory and immunosuppressive signaling and may directly interfere with NK-cell function. This hypothesis integrates oral microbiology, cytokine biology, and tumor immunology and proposes testable pathways linking oral ecological states with cancer-related immune surveillance. It does not suggest that dental caries should be promoted or that conventional caries prevention increases cancer risk.