Smokeless Tobacco and Oral Potentially Malignant Disorders in South Asia: A Systematic Review and Meta-analysis

Oral Potentially Malignant Disorders (OPMDs) are chronic lesions or conditions characterized by a potential for malignant transformation. While recent meta-analyses show that smokeless tobacco (SLT) use is a risk factor for oral cancer in South Asia, there is a lack of pooled evidence regarding SLT use and the development of OPMDs. We searched Medline via PubMed, the Science Citation Index (SCI) via Web of Science, Scopus, CINAHL, Global Index Medicus and Google Scholar databases for relevant literature using a combination of keywords and MeSH terms. Eighteen case-control studies were included in the review, all of which reported significantly elevated risk estimates for OPMDs associated with SLT use. Overall and subgroup, Meta Odds Ratios (mOR) were calculated through a random effects analysis using "generic inverse variance" method in Rev Man 5.3. Heterogeneity was quantified by calculating the I-2 statistic. The mOR for any OPMD with the use of any SLT product was 15.5 [95% Confidence Interval (CI), 9.9-24.2]. Women had a higher risk, mOR = 22.2 (95% CI, 9.1-54.1) compared to men, mOR = 8.7 (95% CI, 2.1-34.8). Betel quid with tobacco carried the highest risk for OPMD, mOR = 16.1 (95% CI, 7.833.5). Although the cumulative evidence is informed by case-control studies only, the magnitude of the pooled estimates and the presence of exposure-response indicate a very strong association between OPMDs and SLT use. In addition to tobacco control, results of this review may help in informing oral cancer control policies in South Asia, since OPMDs lie on the causal pathway for oral cancer. Implications: More than 250 million South and South East Asians use SLT in some form. As cigarettes prices climb up all over the world, more people could potentially take up SLT, particularly in the absence of epidemiological evidence regarding the harmful effects of these products, and SLT being advocated as a means of tobacco harm reduction. Our findings are thus relevant and timely in highlighting the harmful effects of SLT use, with a potential of influencing tobacco control policies in South Asia and beyond.