CYFRA 21-1 and MMP-9 as salivary biomarkers for the detection of oral squamous cell carcinoma: a systematic review of diagnostic test accuracy

Abstract

Tissue biopsy with histopathological examination is still considered the gold standard to diagnose oral squamous cell carcinoma (OSCC). This systematic review explored the diagnostic test accuracy of two salivary biomarkers in adults suspected of OSCC. The Cochrane Library, MEDLINE, and Embase databases were searched for clinical studies evaluating the diagnostic accuracy of salivary biomarkers in detecting OSCC. Studies were eligible for inclusion if only singular salivary biomarkers were evaluated in three or more studies. Studies investigating combined salivary biomarkers or assessing patients with oral potentially malignant disorders only were excluded. The reporting of the review follows the PRISMA checklist. Six studies, recruiting 775 participants, were included in this review for only two salivary biomarkers, cytokeratin 19 fragment (CYFRA 21-1) and matrix metalloproteinase 9 (MMP-9). The sensitivity and specificity (with 95% confidence intervals) for CYFRA 21-1 studies ranged from 0.84 (0.75-0.91) to 0.94 (0.83-0.99) and from 0.84 (0.71-0.93) to 0.96 (0.80-1.00), respectively. In MMP-9 studies, sensitivity (with 95% confidence intervals) ranged from 0.76 (0.67-0.83) to 1.00 (0.78-1.00) and specificity from 0.27 (0.12-0.46) to 1.00 (0.78-1.00). The overall quality of the included studies was poor. Due to a lack of strong and high-quality evidence, considerable uncertainty remains surrounding the use of singular salivary biomarkers for the detection of OSCC.

Keywords: CYFRA 21-1; MMP-9; OSCC; oral cancer; oral squamous cell carcinoma; salivary biomarkers.