MATERIALS AND METHODS: A systematic review was performed in accordance with the 3rd edition of the Centre for Reviews and Dissemination (CRD) and Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. Electronic searches for articles were carried out in the PubMed, Web of Science, and Scopus databases. The quality assessment of the included studies was evaluated using the Newcastle-Ottawa Quality Assessment Scale (NOS) and the new version of the QUADOMICS tool. Meta-analysis was conducted whenever possible. The effect size was presented using the Forest plot, whereas the presence of publication bias was examined through Begg's funnel plot.
RESULTS: A total of nine studies were included in the systematic review. The metabolite profiling was heterogeneous across all the studies. The expression of several salivary metabolites was found to be significantly altered in OPMDs and OCs as compared to healthy controls. Meta-analysis was able to be conducted only for N-acetylglucosamine. There was no significant difference (SMD = 0.15; 95% CI - 0.25-0.56) in the level of N-acetylglucosamine between OPMDs, OC, and the control group.
CONCLUSION: Evidence for N-acetylglucosamine as a salivary biomarker for oral cancer is lacking. Although several salivary metabolites show changes between healthy, OPMDs, and OC, their diagnostic potential cannot be assessed in this review due to a lack of data. Therefore, further high-quality studies with detailed analysis and reporting are required to establish the diagnostic potential of the salivary metabolites in OPMDs and OC.
CLINICAL RELEVANCE: While some salivary metabolites exhibit significant changes in oral potentially malignant disorders (OPMDs) and oral cancer (OC) compared to healthy controls, the current evidence, especially for N-acetylglucosamine, is inadequate to confirm their reliability as diagnostic biomarkers. Additional high-quality studies are needed for a more conclusive assessment of salivary metabolites in oral disease diagnosis.