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Meta-Analysis
. 2014 Nov 20;9(11):e113385.
doi: 10.1371/journal.pone.0113385. eCollection 2014.

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

Bhawna Gupta  1 , Newell W Johnson  2
Affiliations
Meta-Analysis

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

Bhawna Gupta et al. PLoS One. .

Abstract

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 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.

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 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.

Conclusion: 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.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. PRISMA strategy for Systematic review and meta-analysis of association of ST and BQ without tobacco with incidence of oral cancer in South Asia and the Pacific.
Figure 2
Figure 2. Meta-analysis of case-control studies: ST NOS use and incidence of oral cancer.
Figure 3
Figure 3. Meta-analysis of case-control studies: BQ without tobacco use and incidence of oral cancer.
Figure 4
Figure 4. Meta-analysis of cohort studies: ST NOS use and incidence of oral cancer.
Figure 5
Figure 5. Publication bias for case-control studies illustrating the relationship between ST NOS and incidence of oral cancer.
Figure 6
Figure 6. Publication bias for case-control studies illustrating the relationship between BQ without tobacco and incidence of oral cancer.
Figure 7
Figure 7. Publication bias for cohort studies illustrating the relationship ST NOS and incidence of oral cancer.
See this image and copyright information in PMC

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