Systematic Review and Meta-Analysis of Association of Smokeless Tobacco and of Betel Quid without Tobacco with Incidence of Oral Cancer in South Asia and the Pacific

Aim: This systematic review and meta-analysis aimed to critically appraised data from comparable studies leading to quantitative assessment of any independent association between use of oral smokeless tobacco in any form, of betel quid without tobacco and of areca nut with incidence of oral cancer in South Asia and the Pacific. Methods: Studies (case control and/or cohort) were identified by searching Pub Med, CINAHL and Cochrane databases through June 2013 using the keywords oral cancer: chewing tobacco; smokeless tobacco; betel quid; betel quid without tobacco; areca nut; Asia, the Pacific and the reference lists of retrieved articles. A random effects model was used to compute adjusted summary ORRE for the main effect of these habits along with their corresponding 95 % confidence intervals. To quantify the impact of between-study heterogeneity on adjusted main-effect summary ORRE, Higgins ’ H and I2 statistics along with their 95 % uncertainty intervals were used. Funnel plots and Egger’s test were used to evaluate publication bias. Results: Meta-analysis of fifteen case–control studies (4,553 cases; 8,632 controls) and four cohort studies (15,342) which met our inclusion criteria showed that chewing tobacco is significantly and independently associated with an increased risk of squamous-cell carcinoma of the oral cavity (adjusted main-effect summary for case- control studies ORRE = 7.46; 95% CI = 5.86–9.50, P,0.001), (adjusted main-effect summary for cohort studies RR = 5.48; 95 % CI = 2.56–11.71, P,0.001)