Extracellular Vesicles as Biomarkers in Head and Neck Squamous Cell Carcinoma: From Diagnosis to Disease-Free Survival

SIMPLE SUMMARY: Extracellular vesicles are considered intracellular messengers that exchange proteins, lipids, various types of DNA and RNA, etc. They can be properly collected from many kinds of biofluids, such as blood and saliva. Compared to other substances obtained from liquid biopsy, such as cell-free DNA and circulating tumor cells, extracellular vesicles are a better choice to evaluate the disease since the genetic information is protected by their membranous structure, and thus they are more stable for detection. Extracellular vesicles contain less invasive property compared with other substances, and they are easier to collect from extraction with higher efficiency. Moreover, the roles of extracellular vesicles in multiple physiological and pathological processes are more well-known, entitling them to serve as biomarkers for certain cancers, including head and neck squamous cell carcinoma. This review aims to comprehensively present the current clinical trials at several key stages of tumor diagnosis and treatment, as well as their potential to dynamically monitor head and neck cancers during the whole clinical care process. ABSTRACT: Head and neck squamous cell carcinomas (HNSCCs) arising from different anatomical sites present with different incidences and characteristics, which requires a personalized treatment strategy. Despite the extensive research that has conducted on this malignancy, HNSCC still has a poor overall survival rate. Many attempts have been made to improve the outcomes, but one of the bottlenecks is thought to be the lack of an effective biomarker with high sensitivity and specificity. Extracellular vesicles (EVs) are secreted by various cells and participate in a great number of intercellular communications. Based on liquid biopsy, EV detection in several biofluids, such as blood, saliva, and urine, has been applied to identify the existence and progression of a variety of cancers. In HNSCC, tumor-derived EVs exhibit many functionalities by transporting diverse cargoes, which highlights their importance in tumor screening, the determination of multidisciplinary therapy, prediction of prognosis, and evaluation of therapeutic effects. This review illustrates the classification and formation of EV subtypes, the cargoes conveyed by these vesicles, and their respective functions in HNSCC cancer biology, and discloses their potential as biomarkers during the whole process of tumor diagnosis, treatment, and follow-up.