Salivary biomarkers for oral cancer and pre-cancer screening: a review

The objective of the study was to conduct a systematic review of the literature assessing potential salivary biomarkers of oral cancer and pre-cancer and discuss emerging issues and challenges in relation to oral cancer and pre-cancer diagnostics. Search for articles involved the Medline, PubMed, and EMBASE. Specific terms were used from January 1995 to March 2017 by three experts. This search collected 270 articles, of which 105 articles such as reviews, case reports, news, letter to editor, etc. in first round and 117 articles such as publications in other languages than English, non-human studies, etc. were excluded. The remaining 48 articles considered analyzing whole saliva as well as specific gland saliva. Thirty-one studies considered oral stimuli such as eating, drinking, and oral hygiene practices for varied periods of time prior to sample collection. The time of collection of saliva was morning in most studies, but the exact time of collection was not mentioned. Three studies showed to have evaluated the whole saliva without centrifugation. Two-dimensional gel electrophoresis and tandem mass spectrometry were the most commonly used methods. Most of the potential salivary biomarkers of oral cancer are salivary proteins. Combination approach of salivary biomarkers could be used as screening tool to improve early detection and diagnostic precision of oral pre-cancer and cancer. The current findings are of importance for clinicians and researchers to mitigate the challenges in salivary-based diagnosis of oral cancer and to evaluate reliable, specific, and sensitive salivary biomarkers for oral pre-cancer and cancer diagnosis.