Salivary Biomarkers for Detection of Oral Squamous Cell Carcinoma: Current State and Recent Advances

Oral squamous cell carcinoma (OSCC) is the most common malignant neoplasm of the oral cavity. Detection of OSCC is currently based on thorough clinical oral examination combined with biopsy for histological analysis. Most cases of OSCC are not detected until the cancer has developed into advanced stages; thus, a reliable early stage diagnostic marker is needed. This literature review presents an overview of the status of current advances in salivary diagnostics for OSCC. Though many protein and mRNA salivary biomarkers have been identified that can detect OSCC with high sensitivity and specificity, the most discernable findings occur with the use of multiple markers. Studies that incorporate proteomic, transcriptomic, and potentially additional “omics”, including methylomics, need to be initiated to bring technology to clinical applications and allow the best use of saliva in diagnosing OSCC

Proteomics investigation of OSCC-specific salivary biomarkers in a Hungarian population highlights the importance of identification of population-tailored biomarkers.

Oral squamous cell carcinoma (OSCC) accounting for about 90% of malignant oral lesions is the 6th most common malignancy worldwide. Diagnostic delay may contribute to dismal survival rate therefore, there is a need for developing specific and sensitive biomarkers to improve early detection. Hungarian population occupies the top places of statistics regarding OSCC incidence and mortality figures therefore, we aimed at finding potential salivary protein biomarkers suitable for the Hungarian population. In this study we investigated 14 proteins which were previously reported as significantly elevated in saliva of patients with OSCC. In case of IL-1α, IL-1β, IL-6, IL-8, TNF-α and VEGF a Luminex-based multiplex kit was utilized and the salivary concentrations were determined. In case of catalase, profilin-1, S100A9, CD59, galectin-3-bindig protein, CD44, thioredoxin and keratin-19, SRM-based targeted proteomic method was developed and the relative amount of the proteins was determined in the saliva of patients with OSCC and controls. After several rounds of optimization and using stable isotope-containing peptides, we developed an SRM-based method for rapid salivary protein detection. The validation of the selected potential biomarkers by ELISA revealed salivary protein S100A9 and IL-6 as useful protein biomarkers for OSCC detection improving the diagnostic accuracy for OSCC in the Hungarian population.A noninvasive diagnostic method to detect biomarkers useful for the early diagnosis of OSCC was developed. This can be an attractive strategy in screening saliva samples collected in a nation-wide multi-centric study in order to decrease morbidity, mortality, to enhance survival rate and to improve quality of life. The heterogeneity of protein biomarkers found in different ethnic groups presented in the literature highlights the importance of identification of population-tailored protein biomarkers