Oral Microbiome–Host Epigenetic Interactions in Oral Carcinogenesis: A Molecular Perspective

Oral squamous cell carcinoma is still found late, and the tumor microenvironment is complicated enough that treatment often fails even when the diagnosis is timely. While genetic mutations partially account for this pathogenesis, they do not fully explain tumor behavior. Attention has therefore shifted to the microbial community around the tumor, which appears to contribute to malignancy less through the genome than through the host epigenome. This review is about the mechanism rather than about cataloging which species are present. We follow what Porphyromonas gingivalis, Fusobacterium nucleatum and Candida albicans do to DNA methylation, histone modification and non-coding RNA expression in host cells. While chronic inflammation plays a well-established role, bacterial and fungal metabolites also reach chromatin directly, and the resulting changes silence tumor suppressors and release oncogenic signaling in epithelium and stroma alike. We then ask what this means for tumor heterogeneity, for immune escape, and for progression, and we close with the two clinical questions that follow: whether salivary microbial and methylation signatures are usable for early detection, and whether epigenetic drugs can be aimed at the microbial component of the oral tumor microenvironment. In conclusion, the oral microbiome–epigenome axis acts as a crucial driver of tumor progression and microenvironmental immunosuppression. While translating these mechanistic insights into clinical practice necessitates rigorous in vivo validation, integrating microbiota-directed interventions with epigenetic therapies represents a highly promising frontier for the early detection and comprehensive management of OSCC.