Study overview (cohort studies included in systematic review).

<p>Design-HC = Hospital based cohort, PC = Population based cohort.</p><p>Gender- M = Males only, F = Females only.</p><p>Study overview (cohort studies included in systematic review).</p

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

<div><p>Aim</p><p>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.</p><p>Methods</p><p>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 OR_RE 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 OR_RE, 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.</p><p>Results</p><p>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 OR_RE = 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). Furthermore, meta-analysis of fifteen case control studies (4,648 cases; 7,847 controls) has shown betel quid without tobacco to have an independent positive association with oral cancer, with OR = 2.82 (95% CI = 2.35–3.40, P<0.001). This is presumably due to the carcinogenicity of areca nut. There was no significant publication bias.</p><p>Conclusion</p><p>There is convincing evidence that smokeless (aka chewing) tobacco, often used as a component of betel quid, and betel quid without tobacco, are both strong and independent risk factors for oral cancer in these populations. However, studies with better separation of the types of tobacco and the ways in which it is used, and studies with sufficient power to quantify dose-response relationships are still needed.</p></div

Meta-analysis of case-control studies: BQ without tobacco use and incidence of oral cancer.

<p>Meta-analysis of case-control studies: BQ without tobacco use and incidence of oral cancer.</p

Meta-analysis of case-control studies: ST NOS use and incidence of oral cancer.

<p>Meta-analysis of case-control studies: ST NOS use and incidence of oral cancer.</p

Publication bias for case-control studies illustrating the relationship between ST NOS and incidence of oral cancer.

<p>Publication bias for case-control studies illustrating the relationship between ST NOS and incidence of oral cancer.</p

Cancer site.

<p>It is important to note here that the intra oral sites are not listed according to WHO ICD-10-C00-C06, but according to what authors have reported.</p><p>-•These studies did not report sub-site, using descriptors such as oral cancer/cancer of oral cavity.</p><p>-Floor of mouth followed by lip, tongue and buccal mucosa were the most common sites as determined from this systematic review.</p><p>Cancer site.</p

Meta-analysis of cohort studies: ST NOS use and incidence of oral cancer.

<p>Meta-analysis of cohort studies: ST NOS use and incidence of oral cancer.</p

Publication bias for case-control studies illustrating the relationship between BQ without tobacco and incidence of oral cancer.

<p>Publication bias for case-control studies illustrating the relationship between BQ without tobacco and incidence of oral cancer.</p

Publication bias for cohort studies illustrating the relationship ST NOS and incidence of oral cancer.

<p>Publication bias for cohort studies illustrating the relationship ST NOS and incidence of oral cancer.</p

Study overview (case-control studies included in systematic review).

<p>Design- CCH  =  case-control with hospital controls, CCP  =  case-control with population controls.</p><p>Gender- M+F  =  separate data for males and females, M&F =  gender data combined.</p><p>M =  exposure data available only for males.</p><p>SCC =  Squamous cell carcinoma.</p><p>H&N = Head and Neck.</p><p>Study overview (case-control studies included in systematic review).</p