Saikat Mazumder, Debasmita Bhattacharya, Sudhriti Maity, Trisha Dutta, Sayan Chatterjee
Oral squamous cell carcinoma (OSCC) is the most common type of oral cancer, and it is becoming clear that it is a multifactorial disease condition that is affected by microbial dysbiosis. Porphyromonas gingivalis and Candida spp. are keystone periodontal pathogens that have become key disease initiators and progressors in the formation of polymicrobial biofilms in periodontal disease. The biofilms are hyper-virulent, resistant, and cooperate metabolically, leading to chronic inflammation and epithelial remodelling. P. gingivalis, in a mechanistic way, regulates host signaling pathways such as NF- kB, PI3K/Akt, and MAPK to induce anti-apoptotic and proliferative responses, and Candida biofilms trigger carcinogenesis by producing acetaldehyde, disrupting the epithelial barrier, and activating oncogenic pathways. This interaction between bacteria and fungal elements is further synergistic and leads to immune evasion, redox dysbalance, and chronic inflammation, which form a tumor-promoting microenvironment. The implication of emerging evidence also includes the effects of microbial metabolites, quorum sensing, and biofilm architecture in determining the OSCC niche. Notably, such polymicrobial interactions offer new therapeutic avenues, such as anti- biofilm therapy, modulation of microbiomes, and targeted molecular therapy. This chapter thoroughly addresses the mechanistic contributions of P. gingivalis and Candida biofilms to OSCC pathogenesis with a specific focus on their synergistic contribution and potential translational implications in diagnosis, prevention, and treatment.