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. 2021 May 11;11:10012. doi: 10.1038/s41598-021-89476-x

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© The Author(s) 2021

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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Flow diagram of search and study selection process. Following the guidelines of the Meta-analysis of Observational Studies in Epidemiology group (MOOSE), we performed a broad and sensitive search on online databases to identify the studies that examined associations between DNA methylation and HNC associated with risk factors (alcohol, tobacco and HPV infection). A systematic literature search for relevant studies up to June 2020. In this study, we considered the clinical endpoints overall survival (OS) and disease specific survival (DFS) as acceptable outcomes. The prognostic value was demonstrated using hazard ratio (HR) with 95% confidence interval (CI).