Oral Microbiome-Mediated Carcinogenesis in Oral Cavity Cancer: A Narrative Review.

The global impact of oral cavity cancer (OCC) is substantial, given its five-year survival rate of nearly 50%. Tobacco, alcohol, and betel nut consumption are primary risk factors, but OCC can also develop in individuals without these exposures. Recent studies increasingly indicate that the oral microbiome may contribute to the pathogenesis of OCC, especially in the context of poor oral hygiene and periodontal disease. The oral microbiome consists of hundreds of bacterial and fungal species, influenced by factors such as smoking, alcohol, diet, and medications. Smoking disrupts microbial balance and epithelial barriers, contributing to dysbiosis. Studies have linked periodontal pathogens like , , and  to OCC, while certain  species may have protective effects. Microbial alterations are observed in both OCC and precancerous lesions, suggesting a role in early carcinogenesis. The oral microbiome may facilitate carcinogenesis through multiple interrelated mechanisms, including the generation of carcinogenic byproducts (e.g., nitrosamines, acetaldehyde, hydrogen sulfide), persistent inflammatory signaling, immune evasion, resistance to apoptosis, and the activation of epithelial-mesenchymal transition pathways. These factors contribute to DNA damage, genomic instability, and tumor progression. A deeper understanding of how the oral microbiome influences OCC may offer novel strategies for both prevention and clinical management. Future research should focus on microbiome-targeted interventions to reduce OCC risk and improve clinical outcomes.