Integrative meta-analysis of the OSCC microbiome: from niche-specific heterogeneity to universal network and functional signatures

Abstract

Abstract Background While the association between oral squamous cell carcinoma (OSCC) and microbial dysbiosis is well-established, high inter-study heterogeneity has historically hindered the identification of universal biomarkers. Objective To explore the profound influence of anatomical ecological niches on microbial profiles while identifying shared oncogenic signatures across diverse populations. Design An integrative meta-analysis of independent OSCC microbiome cohorts was conducted. Results Our results demonstrate that microbial community composition is predominantly driven by the sampling site rather than the disease state alone, with tissue-derived samples forming a distinct ecological cluster. Despite this site-specific dominance, a consistent core of anaerobic pathogens-including Fusobacterium, Capnocytophaga, and Treponema was significantly enriched in OSCC across multiple datasets. Network-based analysis identified Fusobacterium as top driver of microbial community restructuring. Diagnostically, saliva-based models achieved superior accuracy compared to tissue and mucosal models, suggesting that saliva serves as an integrative reservoir for oral pathological changes. Functional profiling further revealed a significant functional convergence toward pathways essential for rapid bacterial proliferation and environmental adaptation, such as ribosome biogenesis, DNA replication, and flagellar assembly. Conclusions These findings emphasize the necessity of standardizing sampling protocols and provide a robust scientific basis for non-invasive, saliva-based precision diagnostic strategies for OSCC.