Role of Fusobacterium Nucleatum in the Pathogenesis of Oral Squamous Cell Carcinoma: A Systematic Review of Molecular Mechanisms and Signalling Pathways.

OBJECTIVES:To evaluate the mechanisms and signalling pathways involved in the pathogenesis of oral squamous cell carcinoma (OSCC) that are promoted by Fusobacterium nucleatum infection across human participant, in vivo and in vitro studies. DESIGN:This systematic review was conducted in accordance with the PRISMA guidelines to address the question: What mechanisms and potential signalling pathways are implicated in the pathogenesis of OSCC facilitated by F. nucleatum infection, compared with non-infected controls? Searches were performed across three electronic databases: Scopus, Web of Science, and MEDLINE. RESULTS:Sixty-three studies met the inclusion criteria for the systematic review. Studies involving human participants revealed alterations in bacterial genes related to lipopolysaccharide (LPS) synthesis, bacterial mobility and flagellar assembly. Additionally, alteration in host genes including DNA repair, tumour protein P53 (TP53), toll-like receptors and proinflammatory genes such as interleukin (IL)1β, IL8, and IL6 were reported. In vivo studies reported upregulation of cyclin D1 and IL6 following F. nucleatum infection. In vitro studies demonstrated changes in epithelial-mesenchymal transition markers such as E-cadherin, N-cadherin, vimentin, and zinc finger E-box binding homeobox (ZEB)1/2, along with increased expression of inflammatory markers, including IL-8 and IL-6 following F. nucleatum infection. CONCLUSION:The findings from this systematic review highlight a significant molecular response to F. nucleatum infection in oral cancer. The results underscore the complex interaction between F. nucleatum and host molecular pathways, offering valuable insights into how this bacterium may contribute to oral cancer development and progression.