Yu-Chi Cheng, Eren A Keles, David T Wu, David R Walt
Oral-fluid EVs represent a compelling but early-stage diagnostic platform in dentistry. Their successful translation will require rigorous methodological standardization, MISEV-aligned reporting, robust analytical and clinical validation, and deployment strategies suited to either point-of-care or centralized laboratory testing.
OBJECTIVES: To review the diagnostic potential of extracellular vesicles (EVs) in dentistry and evaluate the methodological, translatory, and clinical considerations relevant to their use in oral biofluids.
MATERIALS AND METHODS: This narrative review synthesizes current evidence on EVs in dental diagnostics, focusing on saliva, gingival crevicular fluid (GCF), and peri-implant crevicular fluid (PICF). The review examines EV nomenclature, specimen sources, pre-analytical handling, isolation and characterization methods, diagnostic benchmarks, and clinical evidence across major oral diseases.
RESULTS: EVs are promising biomarkers because they protect molecular cargo and may enrich disease-relevant signals relative to whole biofluids. Current evidence is strongest for oral squamous cell carcinoma, periodontitis, and peri-implant disease, where EV-associated proteins, RNAs, and microbe-derived signals have shown diagnostic potential. Saliva offers a noninvasive and accessible matrix, whereas GCF and PICF provide greater site specificity for localized disease. However, major barriers remain, including inconsistent nomenclature, co-isolation of non-vesicular particles, variability in sample collection and EV enrichment methods, limited assay standardization, and insufficient multi-site clinical validation.
CONCLUSIONS: Oral-fluid EVs represent a compelling but early-stage diagnostic platform in dentistry. Their successful translation will require rigorous methodological standardization, MISEV-aligned reporting, robust analytical and clinical validation, and deployment strategies suited to either point-of-care or centralized laboratory testing.
CLINICAL RELEVANCE: EV-based assays could support earlier, more objective, and minimally invasive diagnosis and monitoring of oral diseases, particularly periodontal disease, peri-implant disease, and oral cancer, if current technical and translational barriers are overcome.