Salivary adjunct tests to determine the need for biopsy for early detection of oral squamous cell carcinoma and potentially malignant disorders

BACKGROUND: Salivary adjunct tests could play a role in the oral cancer diagnostic pathway before a biopsy-confirmed definitive diagnosis. The authors aimed to assess the diagnostic impact and diagnostic test accuracy of salivary adjunct tests for detecting oral potentially malignant disorders and oral squamous cell carcinoma. TYPES OF STUDIES REVIEWED: The authors enhanced and updated the systematic searches from systematic reviews across several databases (MEDical Literature Analysis and Retrieval System Online (MEDLINE), Epistemonikos, Embase, Cochrane Central Register of Controlled Trials) through April 27, 2026. Independent paired reviewers screened and extracted data on diagnostic impact and test accuracy studies in duplicate. The certainty of the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation approach. RESULTS: The authors identified 1 diagnostic test accuracy study but no diagnostic impact studies in people with mucosal abnormalities and those without mucosal abnormalities. The identified study analyzed 4 biomarkers collected from saliva (interleukin-6, interleukin-8, tumor necrosis factor-α, matrix metalloproteinase-9). The reported sensitivity was 0.88, and the specificity was 0.80 (with very low certainty). Likelihood ratios, 95% CIs, and number of true-positive results, false-positive results, true-negative results, and false-negative results were not reported. The reported sensitivity and specificity could not be independently verified without crude data. The positivity threshold for the index test was unclear. CONCLUSIONS AND PRACTICAL IMPLICATIONS: There is a lack of diagnostic test accuracy studies that evaluate salivary adjunct tests in a single cohort of patients with a suspected target condition that report accuracy estimates and person-important outcomes. The available evidence is limited, incompletely reported, and neither reproducible nor applicable, making it unsuitable for informing clinical decision making.