Oral squamous cell carcinoma (OSCC), the predominant pathological subtype of oral cancer accounting for approximately 90% of cases, is characterized by a high recurrence rate and metastatic propensity. Consequently, the 5-year survival rate of affected patients has long remained at a relatively low level of 50%–60%. Microbial dysbiosis is also recognized to have potential associations with enhanced genomic instability of tumor cells and epithelial-mesenchymal transition (EMT). Emerging evidence suggests that intracellular bacteria may act as cryptic pathogenic factors, participating in the initiation and progression of OSCC by driving chronic inflammation, facilitating tumor immune escape, and remodeling the metabolic patterns of tumor cells. Despite advancements in microbiome multi-omics analysis technologies and the development of synthetic biology-driven engineered bacteria, which have offered novel possibilities for precise interventions, the vast majority of these strategies are still in the preclinical validation phase. Their in vivo safety, delivery efficiency, and adaptability to the heterogeneity of the tumor microenvironment all await systematic evaluation. This review aims to systematically synthesize the multiple lines of evidence regarding the involvement of intracellular bacteria in the malignant progression of OSCC, highlighting their potential role as key “collaborators” in tumor evolution. Meanwhile, it explicitly points out that current research is mostly confined to correlation analyses or in vitro functional validation, lacking large-sample prospective cohorts and confirmation of causal mechanisms. Future studies should, on the basis of clarifying the molecular mechanisms underlying microbe-host interactions, prudently assess the potential and risks of microbiome-targeted intervention strategies in clinical applications.
Shi et al. (Mon,) studied this question.