Diagnostic Accuracy of Salivary Biomarkers in Detecting Early Oral Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis

Abstract

Background: Biopsy is the gold standard for oral squamous cell carcinoma (OSCC) diagnosis. Salivary biomarkers provide promising complementary alternative diagnostic adjunct for its simple non-invasive collection and technique and to screen large population. Objective: To summarize and compare the existing evidence on diagnostic accuracy of salivary biomarkers with their estimation method in detecting early oral squamous cell carcinoma. Methods: The review protocol is registered under PROSPERO(CRD42021225704). PubMed, Google Scholar, EBSCOhost were searched from 2000 to 2020 to identify the screening potential of eight salivary biomarkers: mRNA, miRNA, DUSP100, s100P, IL-8, IL-1B, TNF-a and MMP-9. True-positive, false-positive, true-negative, false-negative, sensitivity, specificity values were extracted or calculated if not present for each study. Quality of selected studies was evaluated based on QUADAS 2 tool. Meta-analysis was performed using a bivariate model parameter for the sensitivity and specificity and summary points, summary receiver operating curve (SROC), confidence region, and prediction region were calculated. Results: Eighteen studies were included for qualitative synthesis and out of that 13 for meta-analysis. Sensitivity and specificity were calculated with AUC. For mRNA it was 91% and 90% with 0.96 AUC, miRNA had 91% and 91% with 0.95 AUC for PCR. IL-1B had 46% and 60% with 0.61 AUC, S100p had 45% and 90% with 0.57 AUC for ELISA. IL-8 had 54% and 74% for ELISA and 89% and 90% for PCR with 0.79 AUC and DUSP1 had 32% and 87% for ELISA and 76% and 83% for PCR with 0.83 AUC respectively. Conclusion: Early detection of OSCC was best achieved by screening for salivary mRNA and miRNA estimated by PCR. Further investigation is required into salivary RNA as novel biomarkers and these salivary biomarkers may be potentially used for non-invasive diagnosis of early OSCC.

Personalized Medicine in Oral Oncology: Imaging Methods and Biological Markers to Support Diagnosis of Oral Squamous Cell Carcinoma (OSCC): A Narrative Literature Review

“…In 2022, Shaw et al [ 168 ] meta-analyzed the scientific literature for the quantitative analysis of diagnostic accuracy and applicability of four classes of salivary biomarkers and the relative capability of polymerase chain reaction (PCR) and the enzyme-linked immunosorbent assay (ELISA) to detect them in the saliva. The authors reported results of detecting salivary biomarkers better by PCR than by ELISA; furthermore, the more sensitive and specific biomarkers associated with OSCC were mRNAs, miRNA, and IL-8 (sensitivity and specificity over 89%).…”

“…In the field of omics sciences, the role of salivary proteins associated with OSCC has been widely investigated. Various systematic reviews and meta-analyses have recently summarized this research topic’s state of the art [ 168 , 169 , 170 , 171 , 172 ].…”

Salivary biomarkers related to potentially malignant disorders and oral carcinomas: Brief update

“…Further studies would also be needed to confirm the reliability of salivary screening tests, with an increase in the sample size and multicenter studies, with a combination of several cytokines, and standardized quantification of the same, using reliable and quality reagents, in addition to paired control patients, according to their periodontal health. Shaw et al (2022), in their systematic review and meta-analysis using 13 studies with a total of 1048 patients, found that most of the eight salivary biomarkers (mRNA, miRNA, DUSP100, s100P, IL-8, IL-1B, TNF-a and MMP-9) evaluated in the studies showed good diagnostic accuracy. The authors reported that the detection of mRNA and micro-RNA had a sensitivity of 91% and specificity of 90% when they were detected by the PCR (polymerase chain reaction) technique.…”

Utility of miRNA biomarkers for detection of early head and neck squamous cell carcinoma

“…The use of such biomarkers in detecting HNSCC is still a developing field. Previous studies have reported up/down-regulation of various salivary miRNAs in HNSCC at various stages of disease (15), with sensitivity and specificity of different miRNAs ranging anywhere 14-100% and 38-100% respectively in detecting HNSCC (16). However, there is still not much known about the expression of miRNA by HNSCC in vitro nor miRNA expression difference dependence on HPV status.…”