The Molecular Interplay Between Oral Microbiome and Oral Cancer Pathogenesis

The oral microbiome plays a key role in oral cancer pathogenesis through mechanisms such as chronic inflammation, dysregulated proliferation, and increased tumor invasiveness. Dysbiosis, frequently present in premalignant and malignant lesions, may initiate or accelerate malignant transformation. Oral squamous cell carcinoma (OSCC), representing over 90% of oral cancers and affecting more than 350,000 people worldwide each year, is strongly linked to microbial shifts. Common periodontal pathogens such as Fusobacterium nucleatum and Porphyromonas gingivalis are often enriched in OSCC. These bacteria may promote tumorigenesis by activating NF-κB and STAT3 pathways, suppressing apoptosis, and modulating host immune responses. Additional potential mechanisms include the production of reactive oxygen species (ROS) and genotoxins, inhibition of tumor suppressors such as p53, disruption of cell-cycle regulation via cyclin-dependent kinase pathway, and upregulation of β-catenin and toll-like receptor signaling. These molecular alterations cause DNA damage, immune surveillance evasion, angiogenesis, promoting tumor progression. Microbiota-modulating therapies, such as Lactobacillus probiotics, may complement standard treatments by restoring balance, boosting immunity, and limiting tumor growth. Engineered bacteriotherapy, microbiome-targeted immunomodulators, and microbiota-based diagnostics expand therapeutic options in oral cancer and, combined with advances in precision medicine, may support more personalized treatments and improved outcomes.