101 patients with mild or moderate OED were selected from cases with oral leukoplakia, lichen planus, or chronic discoid erythematosus at Peking University School of Stomatology between 1995 and 2005. All of the patients with OED had been diagnosed pathologically by at least two senior pathologists using the criteria from '2005 WHO Classification System' (Gale et al, 2005). All cases involved primary lesions without any LASER, radiation therapy or chemotherapy. p16 methylation status of OED samples was analyzed with methylation-specific PCR combined with denatured high performance liquid chromatography (Sun et al, 2004). 93 eligible cases with p16-methylated or p16-unmethylated OED were enrolled into the cohort study.