Our study objectives are two-fold: (i) firstly, to investigate the early diagnostic potential of the salivary DNA methylation panel (RASSF1α, p16INK4a, TIMP3, PCQAP 5′ and PCQAP 3′) (ii) secondly, to determine whether this panel is able to discriminate between HPV-negative and HPV-positive HNSCC patients. Here, CDKN2A is linked to head and neck squamous cell carcinoma.