We first evaluated the associations of P16INK4a methylation status with several risk factors for SIL/CC, including HPV infection (Positive vs Negative), smoking habit (Smoker vs Nonsmoker) and early age at diagnosis (< 50 vs ≥ 50) (Table 6), and observed that P16INK4a promoter hypermethylation was significantly associated with smoking habit, (OR = 3.88, 95% CI: 2.13-7.08, P < 0.001) (Figure 5), but was not correlated with HPV infection and early age at diagnosis (Supplementary Figure 2 and 3). Here, CDKN2A is linked to squamous cell intraepithelial neoplasia.