Abstract
(1) Background: Oral cancer (OC) is one of the most frequently diagnosed human cancers and remains a challenge for biologists and clinicians. More than 90% of OC cases are squamous cell carcinomas (OSCCs). Despite the use of modern diagnostic and prognostic methods, the 5-year survival rate remains unsatisfactory due to the late diagnosis of the neoplastic process and its resistance to treatment. This comprehensive review aims to present the latest literature data on the use and effectiveness of saliva as a non-invasive biomarker in patients with oral cancer. (2) Methods: The article reviews the current literature on the use of salivary omics biomarkers as an effective method in diagnosing and modifying treatment in patients with OSCC; the research corpus was acquired from the PubMed/Google/Scopus/Cochrane Library/Web of Science databases in accordance with the Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA 2020) guidelines. (3) Results: The identification of salivary omics biomarkers involved in carcinogenesis and neoplastic transformation may be a potential alternative to traditional invasive diagnostic methods. Saliva, being both an abundant reservoir of organic and inorganic components derived from epithelial cells as well as a cell-free environment, is becoming an interesting diagnostic material for studies in the field of proteomics, genomics, metagenomics, and metabolomics. (4) Conclusions: Saliva-based analysis is a modern and promising method for the early diagnosis and improvement of treatment outcomes in patients with OSCC and oral potentially malignant disorders (OPMDs), with high diagnostic, therapeutic, and prognostic potential.