Microbial biomarkers for OPMD progression.

Oral potentially malignant disorders (OPMDs) present a heterogeneous risk of progression to oral squamous cell carcinoma (OSCC), underscoring the need for reliable, non-invasive biomarkers to aid in clinical stratification. This chapter evaluates the utility of the oral microbiome as a source of predictive biomarkers for OPMD progression. Current evidence indicates that OPMDs and OSCC are frequently associated with microbial dysbiosis, characterized by a shift toward anaerobic, periodontal-associated taxa, such as Fusobacterium and Porphyromonas, and a concomitant depletion of health-associated Streptococcus. However, translating these taxonomic signatures into clinical practice is hindered by overlapping community structures across healthy, premalignant, and malignant mucosal states, alongside significant confounding from periodontal inflammation and lifestyle exposures. Furthermore, the field remains divided on whether this dysbiosis acts as an upstream driver of carcinogenesis or a downstream consequence of tumor-associated microenvironmental selection. To overcome these methodological and biological limitations, this chapter advocates for an ecology-driven, multi-omics approach. By integrating taxonomic profiling with functional readouts like metabolomics and metaproteomics, and contextualizing these signals within host microenvironmental strata (e.g., hypoxia and inflammation), researchers can achieve greater mechanistic interpretability and robustness. Ultimately, microbiome-informed tools are best positioned not as standalone diagnostic tests, but as adjunctive instruments for clinical triage and risk enrichment, provided they are rigorously validated in prospective, longitudinal converter/non-converter cohorts.