Notably, recent work has shown that HNSCC exhibits distinct combinations of EGFR ligand expression such as TGFA, HBEGF, EREG, and AREG, which define highly active EGFR states; in particular, AREG- and EREG-driven subtypes are associated with EMT and local invasion [74]. Here, HBEGF is linked to head and neck squamous cell carcinoma.