To determine whether the observed induction of CXCL4 secretion in THP-1 monocytes may be connected with a sEV-driven regulation of hypoxia-related molecular pathways, the protein expression of HIF-1α and HIF-2α in monocytes was investigated upon incubation with plasma-derived sEVs from HNSCC patients and healthy donors using immunoblot analysis. This evidence concerns the gene PF4 and head and neck squamous cell carcinoma.