Salivary protein biomarkers for the diagnosis of oral squamous cell carcinoma: a systematic review and meta-analysis

Identifying and assessing salivary protein biomarkers for the noninvasive diagnosis of oral squamous cell carcinoma (OSCC) could significantly enhance early detection, guide timely intervention, and ultimately improve patient survival and quality of life. A comprehensive search of PubMed, Google Scholar, and EMBASE databases was conducted to identify studies that assessed the potential of salivary protein biomarkers for screening OSCC. To assess the validity of the studies, two reviewers independently extracted data on sensitivity, specificity, positive and negative likelihood ratios (PLR and NLR), and diagnostic odds ratios (DOR). Owing to the expected variation between studies, a random effects model was used to combine the extracted data. The meta-analysis included 28 studies including 3,507 patients with OSCC and 3,501 control subjects that evaluated 37 salivary protein biomarkers. Pooled analysis across all biomarkers revealed a sensitivity of 0.71 (95 % CI 0.690-0.720), specificity of 0.69 (95 % CI 0.68-0.71), PLR of 3.04 (95 % CI 2.56-3.60), NLR of 0.37 (95 % CI 0.33-0.43), and DOR of 11.7 (95 % CI 8.02-15.29). Further analysis compared five specific biomarkers: interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α), interleukin-8 (IL-8), matrix metalloproteinase-9 (MMP9), and cytokeratin 19 fragment 21-1 (CYFRA21-1). Notably, MMP9 and CYFRA21-1 demonstrated sensitivity of 1.00 and 0.81, respectively, with specificities of 0.58 and 0.91, respectively, and high area under the curve (AUC) values of 0.9932 and 0.9447, respectively. Despite promising results, heterogeneity across studies warrants cautious interpretation. Focusing on promising candidates, this meta-analysis explored the potential of salivary protein biomarkers for diagnosing OSCC. Notably, MMP9 and CYFRA21-1 demonstrated good sensitivity, suggesting their strong potential for further development as noninvasive diagnostic tools.