EVs from head and neck squamous cell carcinoma (HNSCC) were recently described as carriers of ephrin type B receptor 2 (EPHB2), which upon contact with endothelial cells activated cell-associated ephrin B2-mediated effects, a fascinating case for ‘reverse’ signalling by EPHB2 ligands leading to angiogenesis-like responses [170]. This evidence concerns the gene EPHB2 and head and neck squamous cell carcinoma.