Mechanistic pathways of dysbiosis in oral cancer development.

Head and neck cancers develop within a complex microenvironment shaped by both host genetic alterations and microbial communities. Accumulating evidence demonstrates that microbial dysbiosis actively contributes to carcinogenesis by modulating immune responses, inducing chronic inflammation, and promoting immune evasion. Specific microbes can trigger oncogenic signaling pathways-including JAK/STAT, PI3K/AKT, and NF-κB-that drive cell proliferation, survival, and invasiveness. Microbiome-derived metabolites and co-carcinogens further promote DNA damage, epigenetic reprogramming, and metabolic shifts, reinforcing tumor progression and therapy resistance. This chapter reviews the molecular and cellular mechanisms linking the microbiome to tumor initiation and progression, emphasizing interactions between microbes, immune modulation, intracellular signaling, metabolic dysregulation, as well as induced DNA damages.