Table 1_A spatial–microbial–metabolic–immune framework for high-risk oral potentially malignant disorders: an evidence-ranked review for malignant transformation risk stratification.docx

The framework asks whether dysbiosis-associated microbial signals, epithelial barrier-response states, metabolic stress, stromal remodeling, macrophage-centered immunoregulation, altered epithelial immune visibility, and T-cell positioning become locally aligned within candidate mucosal microdomains. SMMI is a conceptual and validation framework rather than an established causal mechanism, fixed anatomical structure, or immediate therapeutic target.

This article is an evidence-ranked conceptual review rather than a systematic review. We distinguish direct human OPMD evidence from OSCC-derived inference, preclinical perturbation data, broader cancer biology, methods papers, and speculative but testable hypotheses. We outline a modular validation roadmap that proceeds from pathology-anchored sampling and contamination-aware microbial localization to hypothesis-selected spatial modules, targeted functional testing, and longitudinal clinical validation.

The near-term translational goal is improved risk stratification and risk-adapted surveillance, rather than ecological intervention. By reframing high-risk OPMDs as spatial oral microbe–host immune-metabolic ecosystems, the SMMI framework provides a cautious structure for hypothesis generation, spatial validation, and clinically relevant risk modeling.</p>