Efficacy of hypermethylated DNA biomarkers in saliva and oral swabs for oral cancer diagnosis: systematic review and meta-analysis

Objectives: This study aims to determine the diagnostic test accuracy (DTA) of hypermethylated DNA biomarkers in saliva and oral swabs for oral squamous cell carcinoma (OSCC) detection from the prevalidation studies available. Materials and Methods: Electronic database searching of PubMed, EMBASE, Cochrane Library, Scopus, Web of Science, and LILACS was conducted to identify relevant articles that were published between January 1, 2000, and August 1, 2020. Results: Meta-analysis was conducted based on 11 of 20 studies selected for review. Included studies had high bias concerns on the QUADAS-2 study assessment tool. We found that salivary and oral swab hypermethylation markers had better specificity than sensitivity for oral cancer detection. Summary sensitivity and specificity (95% CI) of hypermethylation panels were 86.2% (60–96.2) and 90.6% (85.9–93.9) while for individual markers, summary sensitivity and specificity (95% CI) were 70% (56.9–80.5) and 91.9% (80.3–96.9), respectively. Respective positive and negative likelihood ratios for combined markers were 9.2 (5.89–14.36) and 0.15 (0.05–0.5), and 8.61 (3.39–21.87) and 0.33 (0.22–0.49) for single-application biomarkers. Conclusion: DNA hypermethylation biomarkers especially in combination have acceptable DTA that warrants further optimization with rigorous biomarker evaluation methods for conclusive determination of their efficacy