The role of the oral microbiome in oral cancer (OSCC).

This chapter explores the significant role of oral microbiome dysbiosis in oral squamous cell carcinoma (OSCC) pathogenesis, highlighting mechanisms such as chronic inflammation via NF-κB activation by Porphyromonas gingivalis and Fusobacterium nucleatum, production of oncogenic metabolites (for example, acetaldehyde, N-nitrosamines), immune evasion through PD-L1 upregulation and T-cell suppression, and direct carcinogenic effects including epithelial-mesenchymal transition and apoptosis inhibition. In this comprehensive overview, microbes with key role in OSCC pathogenesis, including F. nucleatum (invasion promotion, hypoxia mimicry), P. gingivalis (EMT induction), Capnocytophaga gingivalis (diagnostic potential), and Candida albicans (acetaldehyde synthesis), are examined, alongside interactions with established risk factors. Diagnostic advancements could potentially include salivary biomarkers (IL-6, miRNAs, bacterial panels) and AI-driven models achieving AUC >0.9, with microbial diversity shifts aiding early detection and prognosis. Recent research investigate findings in mycobiome and HPV influences, therapy modulation (e.g., radiotherapy-induced dysbiosis), epigenetic effects, and hypoxia pathways. Challenges include establishing causality, study inconsistencies, and the need for multiomics approaches, with future directions emphasizing longitudinal research, standardized protocols, and microbiome-targeted therapies to enhance OSCC prevention, diagnosis, and management.