ADAMTS18 and Epstein-Barr virus infection: Among them, DNA promoter CpG island hypermethylation was the most frequently reported mechanism in NPC (38, 39), such as RASSF1A, RASSF2A, CDKN2A, ADAMTS18 (5, 40–43), which contributed to the early pathogenesis, even earlier than EBV infection (38, 44).