SYSTEMATIC REVIEW article
Oncol. Rev.
Sec. Oncology Reviews: Reviews
This article is part of the Research TopicPrevention and Early Detection of Oral Cancers - Volume IIView all articles
Smoking and Oral and Pharyngeal Cancer: A Meta-Analysis
Provisionally accepted
Irene Possenti1Stefano Miotti1
Silvano Gallus1
Vincenzo Bagnardi2Werner Garavello2,3Claudia Specchia4Luc JM Smits5
Anna Odone6,7
Alessandra Lugo1*- 1Mario Negri Institute for Pharmacological Research (IRCCS), Milano, Italy
- 2Universita degli Studi di Milano-Bicocca, Milan, Italy
- 3Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy
- 4Universita degli Studi di Brescia, Brescia, Italy
- 5Universiteit Maastricht Care and Public Health Research Institute, Maastricht, Netherlands
- 6Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
- 7Universita di Pavia, Pavia, Italy
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ABSTRACT INTRODUCTION: Oral cavity and pharyngeal cancer (OPC) affects over 580,000 people globally each year, with tobacco and alcohol being key risk factors. This meta-analysis quantifies the excess risk of OPC associated with cigarette smoking and its patterns. METHODS: We carried out a systematic review and meta-analysis of case-control and cohort studies assessing the association between cigarette smoking and OPC risk, including articles published up to February 2025. Using a combined umbrella and traditional review approach, we estimated pooled relative risks (RR) by smoking status, intensity, duration, and time since quitting. RESULTS: Out of 137 eligible articles, 115 original studies were included in this meta-analysis. Relative to never smokers, the pooled risk of OPC was 3.58 (95% CI: 3.03–4.24; n=54) among current smokers, 1.61 (95% CI: 1.44–1.81; n=53) among former smokers, and 2.45 (95% CI: 2.19– 2.75; n=80) among ever smokers. Subsite-specific analyses showed RRs of 3.39 (95% CI: 2.64– 4.35; n=25) for oral cancer and 4.24 (95% CI: 2.96–6.09; n=18) for pharyngeal cancer in current versus never smokers. Risk rose steeply with both smoking intensity and duration, doubling after 6 cigarettes per day or 7 years of smoking, before reaching a plateau around an RR of 5 at 20 cigarettes per day or 20 years. The risk declined nonlinearly with longer time since quitting, with a 50% reduction observed within ten years of cessation. CONCLUSION: Our findings reaffirm the substantial impact of smoking on OPC risk and stress the need for efforts to avoid smoking initiation and support cessation.
Keywords: oral cancer, Pharyngeal cancer, oropharyngeal cancer, cigarette smoking, Dose-response relationship, Meta-analysis
Received: 24 Jul 2025; Accepted: 20 Nov 2025.
Copyright: © 2025 Possenti, Miotti, Gallus, Bagnardi, Garavello, Specchia, Smits, Odone and Lugo. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Alessandra Lugo, alessandra.lugo@marionegri.it
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