Two subsets of CAFs—senescent CAFs (SA β-Gal/p16INK4A high) and non-senescent (SA β-Gal/p16INK4A low) phenotypes—constitute the most abundant subpopulation of immune-active cells in the tumour microenvironment reported to support carcinogenesis by stimulating tumour initiation, angiogenesis, cancer cell growth and proliferation, as well as tumour invasion, progression and metastasis in most solid tumours, including HNSCC. This evidence concerns the gene CDKN2A and head and neck squamous cell carcinoma.