Abstract
OBJECTIVE: To systematically evaluate the compositional changes in the oral bacterial microbiota associated with oral squamous cell carcinoma (OSCC) using next-generation sequencing (NGS) data. METHODS: This systematic review and meta-analysis was prospectively registered with PROSPERO (CRD420251173644) and conducted in accordance with PRISMA guidelines. A comprehensive literature search was performed in PubMed, Web of Science, and Embase up to October 25, 2025. Case-control studies comparing the oral bacterial microbiota of OSCC patients and healthy controls using NGS were included. Study selection, data extraction, and quality assessment were independently performed by two reviewers using the Newcastle-Ottawa Scale (NOS) and the ROBINS-I tool. Standardized mean differences (SMD) with 95% confidence intervals (CI) were calculated using Stata software to compare the relative abundance of microbial taxa at both the phylum and genus levels. Heterogeneity was assessed using the I² statistic, and subgroup analyses were performed based on sample type. RESULTS: Sixteen case-control studies with 1,608 participants (813 OSCC cases and 795 controls) were included. All studies were of moderate to high quality (NOS score ≥ 6). At the phylum level, the OSCC group showed a significantly lower abundance of Actinobacteria (SMD = -0.85, 95% CI: -1.36 to -0.35; P = 0.001) and a significantly higher abundance of Fusobacteria (SMD = 0.61, 95% CI: 0.32 to 0.90; P < 0.001) compared to controls. At the genus level, Fusobacterium, Capnocytophaga, Peptostreptococcus, Alloprevotella, Parvimonas, and Dialister were significantly enriched in the OSCC group. In contrast, Streptococcus, Haemophilus, Rothia, Veillonella, Actinomyces, and Leptotrichia were significantly depleted. Subgroup analysis revealed sample-specific microbial associations: while Fusobacterium was consistently enriched across all sample types, other taxa showed variations dependent on sampling methodology. Sensitivity analyses confirmed the robustness of the results, and no significant publication bias was detected. CONCLUSION: This meta-analysis identifies a distinct dysbiotic oral bacterial microbiota signature in OSCC, characterized by an enrichment of pro-inflammatory and pathogenic genera (e.g., Fusobacterium, Capnocytophaga) and a depletion of health-associated commensals (e.g., Streptococcus, Rothia). These findings provide strong evidence supporting specific microbial taxa as potential biomarkers for OSCC.