Abstract
Oral cancer, predominantly oral squamous cell carcinoma (OSCC), is a multifactorial disease influenced by genetic, environmental, and microbial factors. Among the emerging contributors to oral carcinogenesis, Fusobacterium nucleatum and Porphyromonas gingivalis, two Gram-negative anaerobic bacteria that reside in the human oral cavity as part of the normal microbiota, have gained attention for their pathogenic roles. Both species play key roles in periodontal disease and exhibit significant tumour-promoting activities through distinct and synergistic mechanisms. They modulate the tumor microenvironment by promoting the release of pro-inflammatory cytokines, facilitating immune evasion, and contributing to microbial dysbiosis. Clinical studies have identified their presence in OSCC tissues, correlating with advanced tumor stages, lymph node metastasis, and poor prognosis. Their involvement underscores the critical interplay between oral microbiota and host-pathogen interactions in cancer development. This review highlights the molecular mechanisms through which F. nucleatum and P. gingivalis contribute to oral carcinogenesis, emphasizing the need for further research to explore their diagnostic and therapeutic potential in oral cancer management. Addressing these microbial drivers could pave the way for innovative strategies in cancer prevention and treatment.