Clinical Utility of Small Extracellular Vesicles as Liquid Biopsy for Oral Mucosal Disease Diagnostics: Emerging Perspectives

Some diseases affecting the oral mucosa can be life-threatening and/or associated with life-threatening complications. Conventional diagnostic methods for most oral mucosal diseases are usually employed at a fully established disease state. All these peculiarities usually result in late diagnosis, poor prognosis, poor treatment outcomes, and reduced overall survival rates, hence the need for novel methods for the early detection of these disease conditions. Small extracellular vesicle (sEV)-based diagnosis carries great potential for early diagnosis of oral mucosal diseases, as sEVs reflect the physiological status of their parent cells. sEVs are also widely distributed in body fluids, which helps overcome the problem of inaccessibility in sample or specimen collection in some cases. Furthermore, the composition of sEVs can be used as diagnostic biomarkers for several disease conditions, including oral mucosal diseases. This review critically examines the emerging role of sEVs-derived biomarkers from saliva and blood in the diagnosis of some oral mucosal diseases, such as hand, foot, and mouth disease (HFMD), oral lichen planus (OLP), oral leukoplakia (OL), and oral squamous cell carcinoma (OSCC). It also discusses the need for the validation and standardization of the potential sEV-derived diagnostic biomarkers of these oral mucosal diseases for clinical application.