ANXA5 and neoplasm: Besides miRNAs, differentially expressed proteins in serum EVs can facilitate early detection of metastasis on OSCC.200,201 Serum/salivary Alix levels in EVs are significantly higher in OSCC patients.202 The serum EVs PD-L1 levels in HNC patients are associated with disease activity and progression.203,204 Feng et al.205 examined EV phenotypes via a microfluidic approach and found that OSCC patients had higher levels of EGFR+ salivary EVs compared to healthy individuals, and the ratio of Annexin V+ EGFR+ EVs to Annexin V- EGFR+ EVs was negatively correlated with tumor T stage.