The Prognostic Value of <i>p16</i> Hypermethylation in Cancer: A Meta-Analysis

<div><p>Background</p><p>The prognostic value of <i>p16</i> promoter hypermethylation in cancers has been evaluated for several years while the results remain controversial. We thus performed a systematic review and meta-analysis of studies assessing the impact of <i>p16</i> methylation on overall survival (OS) and disease-free survival (DFS) to clarify this issue.</p><p>Methods</p><p>We searched Pubmed, Embase and ISI web of knowledge to identify studies on the prognostic impact of <i>p16</i> hypermethylation in cancers. A total of 6589 patients from 45 eligible studies were included in the analysis. Pooled hazard ratios (HRs) with 95% confidence interval (95% CI) were calculated to estimate the effect using random-effects model.</p><p>Results</p><p>The analysis indicated that <i>p16</i> hypermethylation had significant association with poor OS of non-small cell lung cancer (NSCLC) (HR 1.74, 95% CI: 1.36–2.22) and colorectal cancer (CRC) (HR 1.80; 95% CI 1.27–2.55). Moreover, the significant correlation was present between <i>p16</i> hypermethylation and DFS of NSCLC (HR 2.04, 95% CI: 1.19–3.50) and head and neck cancer (HR 2.24, 95% CI: 1.35–3.73). Additionally, in the analysis of the studies following REMARK guidelines more rigorously, <i>p16</i> hypermethylation had unfavorable impact on OS of NSCLC (HR 1.79, 95% CI: 1.35–2.39) and CRC (HR 1.96, 1.16–3.34), and on DFS of NSCLC (HR 2.12, 95% CI: 1.21–3.72) and head and neck cancer (HR 2.24, 95% CI: 1.35–3.73).</p><p>Conclusions</p><p><i>p16</i> hypermethylation might be a predictive factor of poor prognosis in some surgically treated cancers, particularly in NSCLC.</p>