Expert Review of Molecular Diagnostics · Nov 5, 2026

Beyond blood: a narrative review of advancements in saliva-based diagnostics

By Mondal S, Das Sharma A, Mandal SK et al.

Introduction Human whole saliva is an accessible, noninvasive biofluid reflecting systemic and oral physiology, offering a viable alternative to invasive venipuncture and its associated pre-analytical vulnerabilities (e.g. ex vivo glycolysis). Areas covered This narrative review synthesizes salivary biomarkers across major clinical domains, focusing on glycemic control (glucose, 1,5-anhydroglucitol, α2-macroglobulin), cardiovascular risk indices (cTnI, hs-CRP, sAA), critical care and sepsis surveillance (IL-10, acute-phase proteins), endocrinology (free steroid hormones), infectious diseases (HIV, HCV, SARS-CoV-2), oncological liquid biopsy (exosomal miRNAs, ctDNA), and neurodegenerative disorders such as Alzheimer’s disease (Aβ42, p-tau₁₈₁, lactoferrin). Analytical modalities – ranging from high-sensitivity immunoassays to wearable electrochemical biosensors and mass spectrometry – are critically evaluated. Furthermore, this review delineates regulatory-cleared diagnostic platforms (FDA PMA/510(k), EUA, CE-IVD, and SAMHSA-certified panels for viral antibodies, late-night salivary cortisol, and toxicology) from emerging discovery-phase panels. Expert opinion Widespread clinical translation remains constrained by unstandardized collection protocols, oral matrix interference, and a lack of normative reference intervals. Transitioning salivary testing into mainstream diagnostics requires three priorities: (1) universal sampling standardization incorporating flow-rate normalization, (2) engineering matrix-matched biosensors tailored for sub-picomolar detection, and (3) rigorous multicenter prospective trials to validate definitive clinical cutoffs, dynamic blood–saliva correlation kinetics, and digital point-of-care integration.

doi.org/10.1080/14737159.2026.2760897PubMed 42986663Biomarkers