Fig. 4 demonstrates that most studies lie above the equal line between tumor tissue and controls, which illustrates the tumor tissue excess. In plasma samples, the methylation frequency ranged from 6% to 74% (median 33%), which showed a significant correlation of P16INK4A promoter methylation with cancer tissue (Correlation coefficient 0.72, 95% CI: 0.27–0.91, P = 0.0059, Fig 5A). The similar correlation was also found between the cancer tissue and sputum/BALF (Correlation coefficient 0.85, 95% CI: 0.35–0.97, P = 0.0082, Fig. 5B). Here, CDKN2A is linked to cancer.