In addition to DNMT expression, high HBx expression has been correlated with the hypermethylation of the promoter of the major tumor suppressor gene p16INK4A and the subsequent reduction in p16 protein expression in non-cancerous tissue but not in HCC tissue suggesting that HBx plays an important role in the early stages of HBV associated HCC (Zhu et al., 2007). Here, CDKN2A is linked to hepatocellular carcinoma.