Usefulness of protein-based salivary markers in the diagnosis of oral potentially malignant disorders: A systematic review and meta-analysis

Abstract

By using a meta-analytical approach, this study aimed to analyse the diagnostic capacity of protein-based biomarkers in saliva for the differential diagnosis of oral potentially malignant disorders (OPMDs) and oral squamous cell carcinoma (OSCC) from healthy individuals as control group (HCG). Articles on protein-based biomarkers in saliva, which provided quantitative expression in individuals with clinical and histopathological diagnosis of OPMD or oral leukoplakia (OL) were considered eligible. Searches were conducted in eight electronic databases. The methodological quality was assessed using the Quality Assessment of Diagnostic Studies tool (QUADAS-2). Functional analysis was also performed. Meta-analyses were performed using the OpenMeta tool (Analyst). Meta-analysis was possible for 4 of the 11 biomarkers studied. Only the carcinoembryonic antigen (CEA) and the soluble fragment of cytokeratin 19 (CYFRA21) were significant for the OSCC/OPMD subgroup, both with a very low heterogeneity. CEA had an OE = 25.854 (CI95%: 13.215–38.492, p< 0.001, I2 = 0) and CYFRA21 had an OE = 9.317 (CI95%: 9.014–9.619, p< 0.001, I2 = 0). For the OPMD/HCG subgroup, only CYFRA21 was significant, with an OE = 3.679 (CI95%: 0.663–6.696, p= 0.017) although with high heterogeneity (I2 = 91.24). The CEA and CYFRA21 markers proved very useful when differentiating OSCC from OPMD. The CYFRA21 was the only protein that was capable of distinguishing between OPMD and healthy controls.

A systematic review of proteomic biomarkers in oral squamous cell cancer

“…Arroyo et al [139] in a recent meta-analysis found 11 biomarkers of which they did meta-analysis for 4. Of these, only carcinoembryonic antigens (CEA) and soluble fragment of cytokeratin 19 (CYFRA21) were found to be significantly associated with oral cancer.…”

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

“…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 ].…”

“…In detail, Arroyo et al [ 172 ] analyzed the diagnostic capacity of salivary proteins as biomarkers for the differential diagnosis of OPMDs and OSCC compared to healthy controls. Their research was published in 2021 and considered, at the end of the selection, eight papers eligible for their purpose, thus reporting a series of potential markers, of which those significantly higher in OSCC/OPMDs than healthy controls, and therefore with diagnostic significance, were carcinoembryonic antigen (CEA) [ 173 , 174 ] and the soluble fragment of cytokeratin 19 (CYFRA21) [ 170 , 171 ].…”

Unmet Needs and Perspectives in Oral Cancer Prevention

“…Minimally invasive technologies for OPMD detection should be prioritized. For pathological diagnosis, the current gold standard, we should (i) develop standardized histopathological criteria encompassing the various histological appearances for reliable diagnosis of OPMD; (ii) implement validated immunohistochemical and molecular biomarkers; (iii) incorporate artificial intelligence for diagnostic support; and (iv) develop and implement objective detection techniques as well as non-invasive alternatives to biopsies (buccal brushes, saliva, buccal rinses, optical techniques) [ 83 , 103 , 104 , 105 , 106 , 107 , 108 , 109 , 110 ].…”