Diagnostic Accuracy and Clinical Utility of Salivary Biomarkers in Oral Squamous Cell Carcinoma: A Meta-Analysis

TL;DR

Salivary biomarkers have moderate accuracy for diagnosing oral cancer but are best used in high-risk groups, not as general screening tools.

Contribution

This meta-analysis evaluates the diagnostic accuracy and clinical utility of salivary biomarkers for oral squamous cell carcinoma in different population settings.

Findings

Salivary biomarkers have pooled sensitivity of 0.64 and specificity of 0.71 for OSCC detection.

They are more effective at identifying positive cases than ruling out disease in high-prevalence settings.

Biomarkers show limited utility for general population screening but may aid in risk-stratified populations.

Abstract

Salivary biomarkers demonstrate moderate diagnostic accuracy and limited clinical utility when applied as complementary tools for OSCC classification in high-prevalence settings where the pre-test probability exceeds 10%. Their overall performance supports a role in their use as risk-stratification instruments in carefully selected patient populations, rather than as stand-alone diagnostics or screening tests for the general population. Notably, these biomarkers exhibit greater detection capacity. The test has greater inclusion than exclusion, meaning it is more effective at identifying potentially positive cases than at reliably ruling out disease. As a consequence, capacity and post-test probabilities remain clinically concerning even after a negative result, particularly in high-risk individuals and high-risk patients.

Background: Oral squamous cell carcinoma (OSCC) remains a major global health burden due to delayed diagnosis. Although salivary biomarkers have been explored in previous meta-analyses, these studies were limited to specific biomarker types. Methods: This study followed PRISMA guidelines and was registered in PROSPERO (CRD 420261296936). PubMed, Scopus, MEDLINE, and CINAHL were searched for diagnostic accuracy studies of salivary biomarkers for OSCC. Studies providing sufficient data to construct 2 × 2 tables were included. Pooled sensitivity, specificity, DOR, and HSROC curves were estimated using a bivariate random-effects model, and study quality was assessed using QUADAS-2. Results: Eighteen studies comprising 1647 participants yielded 45 diagnostic datasets across multiple biomarker classes. The pooled sensitivity and specificity were 0.64 (95% CI: 0.59–0.69) and 0.71 (95% CI: 0.66–0.76), respectively. The pooled DOR was 4.53 (95% CI: 3.18–6.47), indicating moderate discriminatory ability, with an AUC of 0.75 (95% CI: 0.71–0.79). Fagan’s nomogram analysis demonstrated that these biomarkers are not suitable for screening the general population and should be reserved for enriched populations (pre-test probability > 10%). Conclusions: Salivary biomarkers demonstrate moderate but highly heterogeneous diagnostic accuracy. Clinical utility is context-dependent and limited to enriched populations with a baseline probability of OSCC >10%. In screening the general population (prevalence < 0.01%), these tests offer no significant clinical utility. They should be considered complementary triage tools rather than definitive diagnostic modalities.

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