Fusobacterium nucleatum and oral carcinogenesis: A narrative review of mechanistic pathways and clinical implications

Abstract

The possible role of inflammation in cancer development is gaining attention. Fusobacterium nucleatum is a Gram-negative anaerobe frequently found in the oral cavity and has recently been linked to oral squamous cell carcinoma (OSCC). The current review aimed to analyze the existing evidence on F. nucleatum ’s involvement in oral carcinogenesis. A literature search was done using the terms “ Fusobacterium nucleatum ” OR “ F. nucleatum ” AND “OSCC,” “oral cancer” OR “oral squamous cell carcinoma,” in the PubMed and Google Scholar databases. Original studies published between January 2000 and December 2024 were included. Nonopen access publications, conference proceedings, case reports, case series, literature reviews, and systematic reviews were excluded. Six clinical studies and fourteen preclinical studies satisfied the inclusion criteria. These investigations suggest a correlation between F. nucleatum and OSCC, underscoring its potential contribution to tumor development by promoting cell proliferation, invasion, metastasis, angiogenesis, immune evasion, and the activation of proinflammatory signaling pathways, and supporting the growth of cancer stem cells. High levels of F. nucleatum in oral cancer were linked to progression of oral cancer and, paradoxically, improved survival outcomes in some cases, highlighting its complex and site-specific prognostic role. There is a need for greater clinical validation and mechanistic research to enable microbiome-targeted preventive and therapeutic approaches for oral cancer.