Note, however, that p16INK4a is frequently inactivated through hypermethylation of p16INK4a promoter and through deletion at near-p16 loci (Serrano et al, 1993; Xing et al, 1999; Tokunaga et al, 2002). In our study, we found a downregulation of p16INK4a expression in 68% of ESCC cases regardless of HPV presence. Here, CDKN2A is linked to esophageal squamous cell carcinoma.