Association of smokeless tobacco with oral cancer: A review of systematic reviews
More details
Hide details
National Institute of Cancer Prevention and Research, Indian Council of Medical Research, India
Satyanarayana Labani   

National Institute of Cancer Prevention and Research, Indian Council of Medical Research, I–7 Near City Centre Metro Station, Sector 39, Noida, Uttar Pradesh 201301, India
Publish date: 2019-10-08
Submission date: 2019-06-25
Final revision date: 2019-08-16
Acceptance date: 2019-09-25
Tob. Prev. Cessation 2019;5(October):34
Various primary studies and systematic reviews have been conducted to explain the association between smokeless tobacco and oral cancer. This study aims to consolidate and summarize the risk estimates from various systematic reviews with or without meta-analysis to provide the spectrum of estimates on the association between smokeless tobacco use and oral cancer.

A comprehensive literature search was done on various databases (PubMed, Google Scholar, IndMED, and TOXLINE) by two of the authors independently. Both qualitative and quantitative data extraction and analysis were performed for the included systematic reviews. Range of risk estimates was obtained and analyzed as quantitative findings due to the limitation of an overview of reviews for the pooled estimates. CASP (Critical Appraisals Skills Programme) and AMSTAR 2 (A Measurement Tool to Assess Systematic Reviews) tools were used for the quality assessment of the studies included.

In total, 12 systematic reviews with or without meta-analysis were included in the review. There was a positive and strong association of Smokeless Tobacco (SLT) use with oral cancer irrespective of gender, region, and type of smokeless tobacco. The risk estimate for the South–East Asia Region (SEAR) ranged 4.44– 7.90, for Gutkha it was 8.67, while for Paan it ranged 6.3–7.90 and for overall SLT it ranged 1.36–7.90. Risk estimate for females ranged 5.83–14.56.

The study confirmed the association between SLT use and oral cancer. These findings are of high importance, especially to the South-East Asia Region.

The authors thank the reviewers and authors of various systematic reviews that were considered in this review article.
The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none was reported.
There was no source of funding for this research.
SA and SL conceived the review idea. SA and PV independently performed the literature search and data extraction. The analysis was done by SL and PV. The first draft was written by PV and all authors contributed to further versions of the manuscript. SL reviewed the final draft and all authors read and approved the manuscript.
Not commissioned; externally peer reviewed.
National Cancer Institute of National Institutes of Health. Smokeless Tobacco and Cancer. Accessed April 9, 2019.
National Cancer Institute, Centers for Disease Control and Prevention. Smokeless Tobacco and Public Health: A Global Perspective. Bethesda, MD: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention and National Institutes of Health, National Cancer Institute. http://cancercontrol.cancer.go.... Accessed April 9, 2019.
Food and Agriculture Organization of the United Nations. FAOSTAT: Tobacco, unmanufactured. Accessed April 9, 2019.
World Health Organization. WHO Framework Convention on Tobacco Control. Assessed April 9, 2019.
Ministry of Health and Family Welfare. COTPA 2003 and Rules made there under. India: Ministry of Health and Family Welfare, Government of India; 2003. . Accessed April 10, 2019.
Sinha DN, Rizwan SA, Aryal KK, Karki KB, Zaman MM, Gupta PC. Trends of smokeless tobacco use among adults (aged 15-49 years) in Bangladesh, India and Nepal. Asian Pac J Cancer Prev. 2015;16(15):6561-6568. doi:10.7314/APJCP.2015.16.15.6561
World Health Organization. Recommendation on smokeless tobacco products. 2017. Assessed April 9, 2019.
Lipari RN, Van Horn SL. Trends in Smokeless Tobacco Use and Initiation: 2002 to 2014. In: The CBHSQ Report. Rockville (MD): Substance Abuse and Mental Health Services Administration (US); 2013. Accessed April 9, 2019.
Niaz K, Maqbool F, Khan F, Bahadar H, Ismail Hassan F, Abdollahi M. Smokeless tobacco (paan and gutkha) consumption, prevalence, and contribution to oral cancer. Epidemiol Health. 2017;39:e2017009. doi:10.4178/epih.e2017009
World Health Organization. WHO Report on the Global Tobacco Epidemic, 2008. Assessed April 9, 2019.
Edge SB, Compton CC. The American Joint Committee on Cancer: the 7th Edition of the AJCC Cancer Staging Manual and the Future of TNM. Ann Surg Oncol. 2010;17(6):1471-1474. doi:10.1245/s10434-010-0985-4
American Cancer Society. Survival Rates for Oral Cavity and Oropharyngeal Cancer. Assessed April 12, 2019.
Rao SVK, Mejia G, Thomson KR, Logan R. Epidemiology of Oral Cancer in Asia in the Past Decade- An Update (2000-2012). Asian Pac J Cancer Prev. 2013;14(10):5567-5577. doi:10.7314/APJCP.2013.14.10.5567
Mallath MK, Taylor DG, Badwe RA, et al. The growing burden of cancer in India: epidemiology and social context. Lancet Oncol. 2014;15(6):e205-212. doi:10.1016/S1470-2045(14)70115-9
World Health Organization. International Agency for Research on Cancer. IARC. Assessed May 12, 2019.
PRISMA. PRISMA 2009 checklist. http://www.prisma-statement.or.... Accessed April 22, 2019.
Critical Appraisal Skills Programme. CASP Systematic Review Checklist. Accessed March 28, 2019.
Gates A, Gates M, Duarte G, et al. Evaluation of the reliability, usability, and applicability of AMSTAR, AMSTAR 2, and ROBIS: protocol for a descriptive analytic study. Systematic Reviews. 2018;7(1):85. doi:10.1186/s13643-018-0746-1
Shea BJ, Reeves BC, Wells G, et al. AMSTAR 2: a critical appraisal tool for systematic reviews that include randomised or non-randomised studies of healthcare interventions, or both. BMJ. 2017;358:j4008. doi:10.1136/bmj.j4008
Asthana S, Labani S, Kailash U, Sinha DN, MehrotraR. Association of Smokeless Tobacco Use and Oral Cancer: A Systematic Global Review and Meta-Analysis. Nicotine Tob Res. 2019;21(9):1162-1171. doi:10.1093/ntr/nty074
Guha N, Warnakulasuriya S, Vlaanderen J, Straif K. Betel quid chewing and the risk of oral and oropharyngeal cancers: A meta-analysis with implications for cancer control. Int J Cancer. 2014;135(6):1433-1443. doi:10.1002/ijc.28643
Gupta B, Johnson NW. 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. PLoS One. 2014;9(11):e113385. doi:10.1371/journal.pone.0113385
Khan Z, Tönnies J, Müller S. Smokeless tobacco and oral cancer in South Asia: A systematic review with meta-analysis. J Cancer Epidemiol. 2014:394696. doi:10.1155/2014/394696
Lee PN, Hamling J. Systematic review of the relation between smokeless tobacco and cancer in Europe and North America. BMC Medicine. 2009;7(1):36. doi:10.1186/1741-7015-7-36
Petti S, Masood M, Scully C. The Magnitude of Tobacco Smoking-Betel Quid Chewing-Alcohol Drinking Interaction Effect on Oral Cancer in South-East Asia. A Meta-Analysis of Observational Studies. PLoS One. 2013;8(11):e78999. doi:10.1371/journal.pone.0078999
Prasad JB, DharM. Risk of major cancers associated with various forms of tobacco use in India: a systematic review and meta-analysis. J Public Health. 2018;1-11. doi:10.1007/s10389-018-0992-7
Siddiqi K, Shah S, Abbas SM, et al. Global burden of disease due to smokeless tobacco consumption in adults: Analysis of data from 113 countries. BMC Med. 2015;13(1):194. doi:10.1186/s12916-015-0424-2
Sinha DN, Abdulkader RS, Gupta PC. Smokeless tobacco-associated cancers: A systematic review and meta-analysis of Indian studies. Int J Cancer. 2016;138(6):1368-1379. doi:10.1002/ijc.29884
Awan KH, Patil S. Association of smokeless tobacco with oral cancer – evidence from the South Asian Studies: A systematic review. J Coll Physicians Surg Pak. 2016;26(9):775-780. PMID:27671184.
Khan Z, Suliankatchi RA, Heise TL, Dreger S. Naswar (Smokeless Tobacco) Use and the Risk of Oral Cancer in Pakistan: A Systematic Review With Meta-Analysis. Nicotine Tob Res. 2019;21(1):32-40. doi:10.1093/ntr/ntx281
Gupta S, Gupta R, Sinha DN, Mehrotra R. Relationship between type of smokeless tobacco & risk of cancer: A systematic review. Indian J Med Res. 2018;148(1):56-76. doi:10.4103/ijmr.IJMR_2023_17
Critchley JA, Unal B. Health effects associated with smokeless tobacco: A systematic review. Thorax. 2003;58(5):435-443. doi:10.1136/thorax.58.5.435
Wyss AB, Hashibe M, Lee YA et al. Smokeless tobacco use and the risk of head and neck cancer: Pooled analysis of US studies in the INHANCE consortium. Am J Epidemiol. 2016;184(10):703-716. doi:10.1093/aje/kww075
Weitkunat R, Sanders E, Lee PN. Meta-analysis of the relation between European and American smokeless tobacco and oral cancer. BMC Public Health. 2007;7(1):334. doi:10.1186/1471-2458-7-334
Rodu B, Jansson C. Smokeless tobacco and oral cancer: A review of the risks and determinants. Crit Rev Oral Biol Med. 2004;15(5):252-263. doi:10.1177%2F154411130401500502
Boffetta, P., Hecht, S., Gray, N., Gupta, P., & Straif, K. Smokeless tobacco and cancer. Lancet Oncol. 2008;9(7);667-675. doi:10.1016/s1470-2045(08)70173-6