Effects of smokeless tobacco on cancer incidence and mortality: a global systematic review and meta-analysis.

Introduction: The prevalence of smokeless tobacco consumption remains high despite policies on reduction interventions. This study aims to quantify the associations between smokeless tobacco use with cancer incidence and mortality globally.

Methods: We conducted a systematic review and meta-analysis following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and PROSPERO protocol (ID: CRD42023390468). A comprehensive literature search was performed using PubMed, Web of Science, and Scopus databases, covering the period from January 1, 2000, to February 28, 2023. We included peer-reviewed observational studies, specifically case-control and cohort studies, where smokeless tobacco use was the primary exposure and cancer incidence, or mortality were the main outcomes. Three independent reviewers screened titles, abstracts, and full texts, and extracted data from the included studies. Risk of bias was assessed by the same three reviewers. Any disagreements were resolved through discussion with a fourth reviewer. We performed random-effects meta-analyses and assessed heterogeneity and publication bias to ensure the robustness of our findings.

Results: Of the 3,611 articles identified, 80 were included in the final analysis. Increased risks were observed for cancer mortality [Risk Ratio (RR) 1.38, 95% Confidence Interval (CI) 1.22-1.56] and incidence [RR 1.17, 95% CI 1.08-1.27]. The specific cancer sites with increased mortality risk included head and neck cancers, as well as stomach cancer. For cancer incidence, associations were observed with head and neck, oral, esophageal, stomach, and pancreatic cancers. Significant heterogeneity (I statistic 65% to 90%) was observed among most cancer outcomes.

Conclusion: Our study found significant associations between smokeless tobacco use and cancer incidence and mortality. Targeted policy interventions, such as stricter regulations on smokeless tobacco use, are recommended to reduce its consumption and mitigate the associated cancer risks.