Data sources: Medline, Embase, Cancerlit, Toxline were searched, followed by the reference lists of identified reviews and articles.
Study selection: Human cohort or case-control studies in peer-reviewed journals or that were publicly available were selected if they specified study location; examined any form of oral cancer as the outcome; and described use of chewing tobacco, orally used moist snuff or unspecified smokeless tobacco as the exposure. Studies in Asian populations and those with insufficient power where risk estimates and confidence intervals were not reported or could not be calculated were excluded.
Data extraction and synthesis: Standard information was abstracted from each study. Whole-population data were used to estimate numbers of never-smokers. Separate figures for males and females were obtained where possible. Estimates were made of effect size and precision since these were not presented in original studies. Separate meta-analyses were conducted for chewing tobacco, for snuff and for overall smokeless tobacco. Sensitivity analyses for smokers/ nonsmokers were carried out. Heterogeneity was investigated and publication bias assessed using a funnel plot.
Results: The 32 studies meeting the inclusion criteria provided 38 heterogeneous study-specific estimates of odds or relative risk ratios (see Tables 1, 2). An increase in risk was mainly evident in studies conducted before 1980. No increase was seen in studies in Scandinavia. The pattern of estimates suggests some publication bias.
Conclusions: Smokeless tobacco, as used in America or Europe, carries at most a minor increased risk of oral cancer, but elevated risks in specific populations or from specific products cannot definitely be excluded.