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Global burden of disease due to smokeless tobacco consumption in adults: an updated analysis of data from 127 countries

Abstract

Background

Smokeless tobacco (ST) is consumed by more than 300 million people worldwide. The distribution, determinants and health risks of ST differ from that of smoking; hence, there is a need to highlight its distinct health impact. We present the latest estimates of the global burden of disease due to ST use.

Methods

The ST-related disease burden was estimated for all countries reporting its use among adults. Using systematic searches, we first identified country-specific prevalence of ST use in men and women. We then revised our previously published disease risk estimates for oral, pharyngeal and oesophageal cancers and cardiovascular diseases by updating our systematic reviews and meta-analyses of observational studies. The updated country-specific prevalence of ST and disease risk estimates, including data up to 2019, allowed us to revise the population attributable fraction (PAF) for ST for each country. Finally, we estimated the disease burden attributable to ST for each country as a proportion of the DALYs lost and deaths reported in the 2017 Global Burden of Disease study.

Results

ST use in adults was reported in 127 countries; the highest rates of consumption were in South and Southeast Asia. The risk estimates for cancers were also highest in this region. In 2017, at least 2.5 million DALYs and 90,791 lives were lost across the globe due to oral, pharyngeal and oesophageal cancers that can be attributed to ST. Based on risk estimates obtained from the INTERHEART study, over 6 million DALYs and 258,006 lives were lost from ischaemic heart disease that can be attributed to ST. Three-quarters of the ST-related disease burden was among men. Geographically, > 85% of the ST-related burden was in South and Southeast Asia, India accounting for 70%, Pakistan for 7% and Bangladesh for 5% DALYs lost.

Conclusions

ST is used across the globe and poses a major public health threat predominantly in South and Southeast Asia. While our disease risk estimates are based on a limited evidence of modest quality, the likely ST-related disease burden is substantial. In high-burden countries, ST use needs to be regulated through comprehensive implementation of the World Health Organization Framework Convention for Tobacco Control.

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Background

Smokeless tobacco (ST) refers to various tobacco-containing products that are consumed by chewing, keeping in the mouth or sniffing, rather than smoking [1]. ST products of many different sorts are used by people in every inhabited continent of the world (Table 1) [1]. For example, in Africa, toombak and snuff are commonly used, while in South America, chimó is the product of choice. In Australia, indigenous people use pituri or mingkulpa [2], and in Central Asia, nasvay consumption is very common. In North America, plug or snuff are favoured, and even in Western Europe, where ST products are largely banned, there are exemptions allowing people in Nordic countries to use snus [3]. All the above products vary in their preparation methods, composition and associated health risks (Table 1), but it is in South and Southeast Asia where the greatest diversity of ST products exists, accompanied by the highest prevalence of use [4]. Here, the level of cultural acceptability is such that ST products are often served like confectionery at weddings and other social occasions.

Table 1 Smokeless tobacco products consumed most commonly across the world

ST products contain nicotine and are highly addictive. Often, they also contain carcinogens, such as tobacco-specific nitrosamines (TSNA), arsenic, beryllium, cadmium, nickel, chromium, nitrite and nitrate, in varying levels depending on the product [5, 6]. The pH of the products also varies widely, with some (e.g. khaini, zarda) listing slaked lime among their ingredients [7]. Raising the pH in this way increases the absorption of nicotine and enhances the experience of using the ST product, increasing the likelihood of dependence. The elevated pH also increases the absorption of carcinogens, leading to higher toxicity and greater risk of harm [7].

The harmful nature of many ST products, and the fact that 300 million people around the world use ST [8], make ST consumption a global public health issue. Many ST products lead to different types of head and neck cancers [9, 10]. An increased risk of cardiovascular deaths has been reported [11], and its use in pregnancy is associated with stillbirths and low birth weight [12, 13].

Because of the diversity described above, ST should not be considered as a single product, but rather as groups of products with differences in their toxicity and addictiveness, depending on their composition. As a consequence, it is difficult to estimate the global risks of ST to human health and to agree on international policies for ST prevention and control. Several country-specific studies [14, 15] have been carried out, and in 2015, we published an estimate of the global burden of disease associated with ST use [16]. We used a novel approach, whereby we classified ST products according to their availability in different geographical regions of the world. For example, ST products in South Asia pose a much greater risk to health than those available in Nordic countries, where the manufacturing process removes many of the toxins from the finished product [6, 17]. Using this approach, we estimated the worldwide burden of disease attributable to ST consumption, measured in terms of disability adjusted life years (DALYs) lost and the numbers of deaths in 2010 [16]. Here, we update this estimate to include data up to 2019, providing an indication of how the global ST arena has changed in the intervening years.

Methods

Our methods for updating the estimates of ST disease burden were broadly the same as those used in our earlier publication; these are well described elsewhere [16]. Here, we will summarise these methods and explain any modification made, particularly in relation to the revised timelines. We assessed disease burden for individual countries by varying their populations’ exposure to ST, using the comparative risk assessment method [15]. These individual estimates were then summarised for 14 World Health Organization (WHO) sub-regions (Additional file 1: Appendix 1) as well as for the world.

We first searched the literature to identify the latest point prevalence of ST use among adults ≥ 15 years in men and women for each country (see Additional file 1: Appendix 2 for detailed methods). We searched for the latest estimates for x countries included in our previous study as well as those additional y countries where estimates have been made available since 2014 for the first time. We derived single estimates for each country preferring nationally representative surveys using internationally comparable methods over non-standardised national or sub-national surveys.

We also updated risk estimates for individual diseases caused by ST; however, we kept to the original list of conditions, i.e. cancers of the oral cavity, pharynx and oesophagus, ischemic heart disease and stroke. We only searched for papers published since our last literature search; our updated search strategies can be found in Additional file 1: Appendix 3. As before, all searches and data extraction were independently scrutinised by a second researcher and any discrepancies were arbitrated by a third researcher. All case definitions for diseases and exposure (ST use) used in the retrieved articles were checked for accuracy and consistency and all analyses undertaken in these studies were assessed to see if they controlled for key confounders (mainly smoking and alcohol). We assessed study quality using the Newcastle-Ottawa Scale for assessing non-randomised studies in meta-analysis [24]. For all new studies, we log transformed their risk estimates and 95% confidence intervals to effect sizes and standard errors and added these to the rerun of our random-effects meta-analyses to estimate pooled risk estimates for individual conditions. Where possible, we pooled effect sizes to obtain country-specific risk estimates. For all outcomes in the meta-analyses, we conducted a GRADE assessment to assess the quality of evidence. We also pooled these effect sizes to obtain non-specific global risk estimates. Given that the risk varies from country to country, depending upon which products are locally popular, we used country-specific risk estimates where possible. In countries with no estimates, we used estimates of those countries where similar ST products were consumed. For other countries without estimates that consumed ST products known to contain high levels of TSNAs, we applied non-specific global estimates. Where no information was available on the composition of ST, we did not apply any estimates. Details on how these statistically significant estimates were applied to each WHO sub-region can be found in web Additional file 1: Appendix 4.

Based on the extent to which the included studies adjusted for potential confounders, we categorised them as ‘best-adjusted’ and ‘others’. We carried out a sensitivity analysis for all risks and attributable disease burden estimates including only ‘best-adjusted’ studies. A sensitivity analysis was also carried out by estimating risk estimates separating out cohort from case-control studies.

For each country, we used their point prevalence of ST use and the allocated risk estimate for each condition to estimate its population attributable fraction (PAF) as below:

$$ {\displaystyle \begin{array}{c}\mathrm{PAF}={\mathrm{P}}_{\mathrm{e}}\left({\mathrm{RR}}_{\mathrm{e}}-1\right)/\left[1+{\mathrm{P}}_{\mathrm{e}}\left({\mathrm{RR}}_{\mathrm{e}}-1\right)\right]\\ {}{\mathrm{P}}_{\mathrm{e}}=\Pr \mathrm{evalence}\kern0.75em {\mathrm{RR}}_{\mathrm{e}}=\operatorname{Re}\mathrm{lative}\ \mathrm{risk}\end{array}} $$

Using the 2017 Global Burden of Disease (GBD) Study, we also extracted the total disease burden (B) in terms of number of deaths and DALYs lost due to the conditions associated with ST use for both men and women. The attributable burden (AB) due to ST was then estimated in deaths and DALYs lost for these conditions for both men and women using the following equation.

$$ \mathrm{AB}=\mathrm{PAF}\times \mathrm{B} $$

Results

ST consumption was reported in 127 countries (Fig. 1). These estimates were extracted from nationally representative cross-sectional surveys conducted either as part of international (97/127) or national (30/127) health and tobacco surveillance (Additional file 1: Appendix 5a). A variety of age ranges (as young as 15 or as old as 89, including no upper age limit) were used to define adults.

Fig. 1
figure 1

Smokeless tobacco prevalence among men and women

ST consumption was more common among males than females in 95 countries (Table 2). Among males, Myanmar (62.2%), Nepal (31.3%), India (29.6%), Bhutan (26.5%) and Sri Lanka (26.0%) had the highest consumption rates. Among females, Mauritania (28.3%), Timor Leste (26.8%), Bangladesh (24.8%), Myanmar (24.1%) and Madagascar (19.6%) had the highest consumption rates. Within Europe, Sweden (25.0% males, 7.0% females) and Norway (20.1% males, 6.0% females) had the highest ST (snus) consumption rates.

Table 2 Prevalence of smokeless tobacco use (%) in different countries of the world according to WHO sub-regional classification

Our post-2014 systematic literature search identified an additional four studies demonstrating a causal association between ST and oral cancer; these included two Pakistan-based and one India-based case-control studies and one US-based cohort study (Table 3). No new studies were found for pharyngeal and oesophageal cancers. PRISMA flow diagrams describing the selection process of the studies identified in the literature searches are provided in Additional file 1: Appendix 5b,c. By adding the new studies to the list of studies selected in our first estimates and revising the meta-analyses, we found that the pooled estimates were statistically significant for cancers of the mouth (Fig. 2). The non-specific pooled estimate for oral cancers, based on 36 studies, were 3.94 (95% CI 2.70–5.76). The country-specific relative risk for oral cancers for India was higher (RR 5.32, 95% CI 3.53–8.02) than no-specific estimates and for the USA remained statistically insignificant (RR 0.95, 95% CI 0.70–1.28). Since no new studies were added for pharyngeal and oesophageal cancers, their non-specific risk estimates of 2.23 (95% CI 1.55–3.20) and 2.17 (95% CI 1.70–2.78) remained as per our original estimates, respectively. For cardiovascular diseases, we identified another three Swedish studies for ischaemic heart disease and another two (one in Asia and one in Sweden) for stroke (Table 3). In the absence of any new non-Swedish studies on ischaemic heart disease (Fig. 3), we considered the relative risk (adjusted odds ratio 1.57, 95% CI 1.24–1.99) of myocardial infarction due to ST identified in the 52-country INTERHEART study [35] (conducted across nine WHO regions) as a valid estimate. However, the country-specific (Sweden) relative risk for ischaemic heart disease (RR 0.94, 95% CI 0.87–1.03) and both country-specific (RR 1.02, 95% CI 0.93–1.13 [Sweden]) and non-specific relative risks for stroke (RR 1.03, 95% CI 0.94–1.14) remained statistically insignificant. The GRADE assessment was moderate for oral, pharyngeal and oesophageal cancers and low for IHD (see Additional file 1: Appendix 7).

Table 3 Smokeless tobacco use and risk of cancers, ischaemic heart disease, and stroke—studies included in meta-analysis
Fig. 2
figure 2

Risk estimates for oral cancers among ever ST users

Fig. 3
figure 3

Risk estimates for cardiovascular diseases (ischaemic heart disease, stroke) among ever ST users

We found that most of the included studies adjusted for potential confounders (35/38 for oral, 10/10 for pharyngeal and 15/16 for oesophageal cancers; and 13/16 for IHD) and classified as providing ‘best adjusted’ estimates. According to a sensitivity analysis restricted to only ‘best-adjusted’ studies, the overall risk estimates (RR/OR) for oral cancer increased from 3.94 to 4.46 and for oesophageal cancer from 2.17 to 2.22 (see Additional file 1: sensitivity analysis #1). Separate risk estimates for cohort and case-control studies are included in the Additional file 1: sensitivity analysis #2).

The above risk estimates were included in the mathematical model to estimate the population attributable fraction (PAF), as follows (also see Additional file 1, Appendix 4 for detailed justification): For oral, pharyngeal and oesophageal cancers, Sweden- and US-based country-specific risk estimates were applied to Europe A and America A regions, respectively. Similarly, India-based country-specific risk estimates were applied to Southeast Asia B and D and Western Pacific B regions. No risk estimates were applied to Europe C due to the non-existence of any risk estimates or information about the toxicity of ST products. For all other regions, non-specific country estimates were applied. A few exceptions were made to the above assumptions: a Pakistan-based country-specific estimate was applied for oral cancers for Pakistan and an India-based estimate for the other two cancers; for the UK, India-based country specific estimates were applied due to the predominant use of South Asian products in the country. For ischaemic heart disease, the INTERHEART disease estimates were applied to all WHO regions except two, i.e. Europe A due to the availability of Sweden-based country specific estimates and Europe C due to the non-availability of relevant information. As previously stated, an exception was made for the UK and the INTERHEART estimates were applied.

According to our 2017 estimates, 2,556,810 DALYs lost and 90,791 deaths due to oral, pharyngeal and oesophageal cancers can be attributed to ST use across the globe (Table 4). By applying risk estimates obtained from the INTERHEART study, 6,135,017 DALYs lost and 258,006 deaths from ischaemic heart disease can be attributed to ST use. The overall global disease burden due to ST use amounts to 8,691,827 DALYs lost and 348,798 deaths. The attributable disease burden estimates when restricted to only ‘best adjusted’ studies, did not change significantly; the DALYs lost attributable to ST increased to 8,698,142 and deaths to 349,222.

Table 4 Number of deaths and DALYs lost from SLT use in 2017, by WHO sub-region as defined in Additional file 1: Appendix 1

Among these figures, three quarters of the total disease burden was among men. Geographically, > 85% of the disease burden was in South and Southeast Asia, India accounting for 70%, Pakistan for 7% and Bangladesh for 5% DALYs lost due to ST use (Additional file 1: Appendix 6).

Discussion

ST consumption is now reported in at least two thirds of all countries; however, health risks and the overall disease burden attributable to ST use vary widely depending on the composition, preparation and consumption of these products. Southeast Asian countries share the highest disease burden not only due to the popularity of ST but also due to the carcinogenic properties of ST products. In countries (e.g. Sweden) where ST products are heavily regulated for their composition and the levels of TSNAs, the risk to the population is minimal.

We found ST prevalence figures in 12 countries that did not previously report ST use; new figures were also obtained for 55 countries included in the previous estimates [16]. Among these 55 countries: 19 reported a reduction in ST use among both men and women (e.g. Bangladesh, India, Nepal), 14 only among men (e.g. Laos, Pakistan) and eight only among women (e.g. Bhutan, Sri Lanka) (Fig. 4a, b). On the other hand, 13 countries showed an incline in ST use among both men and women (e.g. Indonesia, Myanmar, Malaysia, Timor Leste) and one country (Sweden) among men only. Overall, our updated ST-related disease burden in 2017 was substantially higher than that for 2010—by approximately 50% for cancers and 25% for ischaemic heart disease. This occurred despite a substantial reduction in ST prevalence in India (constituting 70% of the disease burden) and little change in the disease risk estimates. We are now reporting ST use in 12 more countries; however, the main reason for the increased burden of disease was a global rise in the total mortality and DALYs lost—oral, pharyngeal and oesophageal cancers, in particular. The disease burden due to these cancers lags several decades behind the risk exposure. Therefore, a significant reduction in ST-related disease burden as a result of a reduced prevalence will not become apparent for some time to come. Among other studies estimating ST-related global disease burden, our mortality estimates were far more conservative than those reported by Sinha et al. (652,494 deaths); however, their methods were different from ours [9]. Moreover, Sinha et al.’s estimates included a number of additional diseases such as cervical cancer, stomach cancer and stroke. None of these risks were substantiated in our systematic reviews and meta-analyses. On the other hand, our estimates of 2,556,810 DALYs lost and 90,791 deaths due to cancers are close to those estimated by the GBD Study for 2017, i.e.1,890,882 DALYs lost and 75,962 deaths due to cancers [91]. A reason for the slight difference between these two estimates might be that ours included pharyngeal cancers in the estimates while GBD Study only included oral and oesophageal cancers.

Fig. 4
figure 4

a Countries with a proportional change in female ST use between 2015 and 2020 estimates. b Countries with a proportional change in male ST use between 2015 and 2020 estimates

Our methods have several limitations. These have been described in detail elsewhere [16] but are summarised here. Our estimates were limited by the availability of reliable data and caveated by several assumptions. The ST use prevalence data were not available for a third of countries despite reports of ST use there. Where prevalence data were available, there were very few studies providing country-specific disease risks—a particular limitation in Africa and South America. In the absence of country-specific risk estimates, the model relied on assuming that countries that share similar ST products also share similar disease risks. For example, oral cancers risk estimates were only available from five countries (India, Norway, Pakistan, Sweden and the USA). For other countries, the extrapolated risks were based on similarities between ST products sold there and in the above five countries. The estimates for ischemic heart disease must be interpreted with caution, in particular, as the risk estimates for most countries were extrapolated from a single (albeit multi-country) study (INTERHEART). However, we excluded those regions from the above extrapolation where the INTERHEART study was not conducted. As previously noted, the total disease burden observed in 2017 is a consequence of risk exposure over several decades. Therefore, the attributable risk based on the prevalence figures gathered in the last few years may not be accurate. If ST prevalence has been declining in a country over the last few decades, the disease burden obtained by applying more recent prevalence figures may underestimate attributable disease burden. This may well be the case in India where ST use has declined by 17% between the 2009 and 2017 GATS surveys [92]. On the other hand, if ST use is on the rise (e.g. in Timor Leste), the attributable disease burden for 2017 could be an overestimate.

While we found a few more recent ST prevalence surveys and observational studies on the risks associated with ST use, big evidence gaps still remain. The ST surveillance data for many countries are either absent or outdated. The biggest gap is in the lack of observational studies on the risks associated with various types of ST used both within and between countries. While longitudinal studies take time, global surveillance of ST products, their chemical composition and risk profile can help improve the precision of future estimates. As cancer registries become more established around the globe, their secondary data analysis can also provide opportunities to estimate ST-related risks.

ST is the main form of tobacco consumption by almost a quarter of all tobacco users in the world. Yet, its regulation and control lags behind that of cigarettes. The diversity in the composition and toxicity of ST products and the role of both formal and informal sectors in its production, distribution and sale make ST regulation a particular challenge. In a recent policy review of 180 countries that are signatories to WHO FCTC, we found that only a handful of countries have addressed ST control at par with cigarettes [93]. The regulatory bar is often much lower for ST than cigarettes [94]. Where ST control policies are present, there are gaps in their enforcement [95]. On the other hand, Sweden has demonstrated what can be achieved through strong regulations; ST-related harm has not only been reduced significantly, but snus is now used to reduce harm from smoking. Countries where ST use is popular and poses risks to health need to prioritise ST control and apply WHO FCTC articles comprehensively and evenly across all forms of tobacco.

Conclusions

ST is consumed across the globe and poses a major public health threat predominantly in South and Southeast Asia. While our disease risk estimates are based on a limited number of studies with modest quality, the likely disease burden attributable to ST is substantial. In high-burden countries, ST use needs to be regulated through comprehensive implementation and enforcement of the WHO FCTC.

Availability of data and materials

All data generated or analysed during this study are included in this published article and its supplementary information file 1.

Abbreviations

CI:

Confidence intervals

DALYs:

Disability-adjusted life years

DHS:

Demographic and Health Surveys

GATS:

Global Adult Tobacco Survey

ICS:

Individual Country Survey

PAF:

Population attributable fraction

SEBS:

Special Europe Barometer Survey

ST:

Smokeless tobacco

STEPS:

STEPwise Approach to Surveillance

TSNA:

Tobacco-specific nitrosamines

WHO:

World Health Organization

References

  1. National Cancer Institute and Centers for Disease Control and Prevention. Smokeless tobacco and public health: a global perspective. U.S. Department of Health and Human Services, Centers for Disease Control and Prevention and National Institutes of Health, National Cancer Institute; 2014. Bethesda, MD NIH Publication No 14–-7983. https://cancercontrol.cancer.gov/brp/tcrb/global-perspective/SmokelessTobaccoAndPublicHealth.pdf.

  2. Moghbel N, Ryu B, Cabot PJ, Ratsch A, Steadman KJ. In vitro cytotoxicity of Nicotiana gossei leaves, used in the Australian Aboriginal smokeless tobacco known as pituri or mingkulpa. Toxicol Lett. 2016;254:45–51.

    CAS  PubMed  Google Scholar 

  3. Maki J. The incentives created by a harm reduction approach to smoking cessation: snus and smoking in Sweden and Finland. Int J Drug Policy. 2015;26:569–74.

    PubMed  Google Scholar 

  4. Palipudi K, Rizwan SA, Sinha DN, Andes LJ, Amarchand R, Krishnan A, et al. Prevalence and sociodemographic determinants of tobacco use in four countries of the World Health Organization: South-East Asia region: findings from the Global Adult Tobacco Survey. Indian J Cancer. 2014;51(Suppl 1):S24–32.

    PubMed  Google Scholar 

  5. IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, World Health Organization, International Agency for Research on Cancer. Smokeless Tobacco and Some Tobacco-specific N-nitrosamines. Lyon: World Health Organization; 2007. https://monographs.iarc.fr/wp-content/uploads/2018/06/mono89.pdf.

  6. Stanfill SB, Connolly GN, Zhang L, Jia LT, Henningfield JE, Richter P, et al. Global surveillance of oral tobacco products: total nicotine, unionised nicotine and tobacco-specific N-nitrosamines. Tob Control. 2011;20:e2.

    PubMed  Google Scholar 

  7. Sankhla B, Kachhwaha K, Hussain SY, Saxena S, Sireesha SK, Bhargava A. Genotoxic and carcinogenic effect of gutkha: a fast-growing smokeless tobacco. Addict Health. 2018;10:52–63.

    PubMed  PubMed Central  Google Scholar 

  8. National Cancer Institute, Division of Cancer Control, Population Science. Smokeless tobacco and public health: a global perspective | BRP | DCCPS/NCI/NIH. https://cancercontrol.cancer.gov/brp/tcrb/global-perspective/. Accessed 18 Apr 2020. Accessed 18 Apr 2020.

  9. Sinha DN, Suliankatchi RA, Gupta PC, Thamarangsi T, Agarwal N, Parascandola M, et al. Global burden of all-cause and cause-specific mortality due to smokeless tobacco use: systematic review and meta-analysis. Tob Control. 2018;27:35–42.

    PubMed  Google Scholar 

  10. Zhou J, Michaud DS, Langevin SM, McClean MD, Eliot M, Kelsey KT. Smokeless tobacco and risk of head and neck cancer: evidence from a case-control study in New England. Int J Cancer. 2013;132:1911–7.

    CAS  PubMed  Google Scholar 

  11. Vidyasagaran AL, Siddiqi K, Kanaan M. Use of smokeless tobacco and risk of cardiovascular disease: a systematic review and meta-analysis. Eur J Prev Cardiol. 2016;23:1970–81.

    PubMed  Google Scholar 

  12. Inamdar AS, Croucher RE, Chokhandre MK, Mashyakhy MH, Marinho VCC. Maternal smokeless tobacco use in pregnancy and adverse health outcomes in newborns: a systematic review. Nicotine Tob Res. 2015;17:1058–66.

    PubMed  Google Scholar 

  13. Gupta PC, Subramoney S. Smokeless tobacco use and risk of stillbirth: a cohort study in Mumbai. India Epidemiology. 2006;17:47–51.

    PubMed  Google Scholar 

  14. Ezzati M, Lopez AD, Rodgers A, Vander Hoorn S, Murray CJL, Comparative Risk Assessment Collaborating Group. Selected major risk factors and global and regional burden of disease. Lancet. 2002;360:1347–60.

    PubMed  Google Scholar 

  15. Lim SS, Vos T, Flaxman AD, Danaei G, Shibuya K, Adair-Rohani H, et al. A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012;380:2224–60.

    PubMed  PubMed Central  Google Scholar 

  16. Siddiqi K, Shah S, Abbas SM, Vidyasagaran A, Jawad M, Dogar O, et al. Global burden of disease due to smokeless tobacco consumption in adults: analysis of data from 113 countries. BMC Med. 2015;13:194.

    PubMed  PubMed Central  Google Scholar 

  17. Lee PN. Epidemiological evidence relating snus to health – an updated review based on recent publications. Harm Reduction J. 2013;10:36. https://0-doi-org.brum.beds.ac.uk/10.1186/1477-7517-10-36.

    Article  CAS  Google Scholar 

  18. Hearn BA, Renner CC, Ding YS, Vaughan-Watson C, Stanfill SB, Zhang L, et al. Chemical analysis of Alaskan Iq’mik smokeless tobacco. Nicotine Tob Res. 2013;15:1283–8.

    CAS  PubMed  Google Scholar 

  19. Lawler TS, Stanfill SB, Zhang L, Ashley DL, Watson CH. Chemical characterization of domestic oral tobacco products: total nicotine, pH, unprotonated nicotine and tobacco-specific N-nitrosamines. Food Chem Toxicol. 2013;57:380–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Stanfill SB, Oliveira da Silva AL, Lisko JG, Lawler TS, Kuklenyik P, Tyx RE, et al. Comprehensive chemical characterization of Rapé tobacco products: nicotine, un-ionized nicotine, tobacco-specific N’-nitrosamines, polycyclic aromatic hydrocarbons, and flavor constituents. Food Chem Toxicol. 2015;82:50–8.

  21. Al-Mukhaini NM, Ba-Omar TA, Eltayeb EA, Al-Shehi AH. Characterisation of nicotine and cancer-enhancing anions in the common smokeless tobacco Afzal in Oman. Sultan Qaboos Univ Med J. 2015;15:e469–76.

    PubMed  PubMed Central  Google Scholar 

  22. Al-Mukhaini N, Ba-Omar T, Eltayeb EA, Al-Shehi AA. Analysis of tobacco-specific nitrosamines in the common smokeless tobacco Afzal in Oman. Sultan Qaboos Univ Med J. 2016;16:e20–6.

    PubMed  PubMed Central  Google Scholar 

  23. Ratsch AM, Mason A, Rive L, Bogossian FE, Steadman KJ. The Pituri Learning Circle: central Australian Aboriginal women’s knowledge and practices around the use of Nicotiana spp. as a chewing tobacco. Rural Remote Health. 2017;17:4044.

    PubMed  Google Scholar 

  24. Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol. 2010;25:603–5. https://0-doi-org.brum.beds.ac.uk/10.1007/s10654-010-9491-z.

    Article  PubMed  Google Scholar 

  25. World Health Organization WHO report on the global tobacco epidemic, 2017: Monitoring tobacco use and prevention policies. World Health Organization; 2017.

  26. STEPS Country Reports. http://www.who.int/chp/steps/reports/en/..

  27. Global Adult Tobacco Survey. http://www.who.int/tobacco/surveillance/gats/en/.

  28. Sreeramareddy CT, Pradhan PM, Sin S. Prevalence, distribution, and social determinants of tobacco use in 30 sub-Saharan African countries. BMC Med. 2014;12:243.

    PubMed  PubMed Central  Google Scholar 

  29. Ansara DL, Arnold F, Kishor S, Hsia J, Kaufmann R. Tobacco use by men and women in 49 countries with demographic and health surveys. ICF International; 2013.

    Google Scholar 

  30. World Health Organization. WHO Report on the Global Tobacco Epidemic, 2013: Enforcing bans on tobacco advertising, promotion and sponsorship. World Health Organization; 2013.

  31. Health Canada. Canadian tobacco, alcohol and drugs survey (CTADS): summary of results for 2015. 2016.

    Google Scholar 

  32. SAMHSA. Results from the 2015 national survey on drug use and health: detailed tables. Rockville: SAMHSA Office of Applied Studies; 2016. https://www.samhsa.gov/data/sites/default/files/NSDUH-DetTabs-2015/NSDUH-DetTabs-2015/NSDUH-DetTabs-2015.pdf.

    Google Scholar 

  33. Agaku IT, Filippidis FT, Vardavas CI, Odukoya OO, Awopegba AJ, Ayo-Yusuf OA, et al. Poly-tobacco use among adults in 44 countries during 2008-2012: evidence for an integrative and comprehensive approach in tobacco control. Drug Alcohol Depend. 2014;139:60–70.

    PubMed  Google Scholar 

  34. World Health Organization. National survey for non-communicable disease risk factors and injuries: using WHO STEPS approach in Timor-Leste--2014. 2014;5224. http://apps.who.int/iris/bitstream/10665/204350/5B.

  35. Teo KK, Ounpuu S, Hawken S, Pandey MR, Valentin V, Hunt D, et al. Tobacco use and risk of myocardial infarction in 52 countries in the INTERHEART study: a case-control study. Lancet. 2006;368:1474–547X (Electronic):647–58.

    Google Scholar 

  36. Anantharaman D, Chaubal PM, Kannan S, Bhisey RA, Mahimkar MB. Susceptibility to oral cancer by genetic polymorphisms at CYP1A1, GSTM1 and GSTT1 loci among Indians: tobacco exposure as a risk modulator. Carcinogenesis. 2007;28:1455–62.

    CAS  PubMed  Google Scholar 

  37. Balaram P, Sridhar H, Rajkumar T, Vaccarella S, Herrero R, Nandakumar A, et al. Oral cancer in southern India: the influence of smoking, drinking, paan-chewing and oral hygiene. Int J Cancer. 2002;98:440–5.

    CAS  PubMed  Google Scholar 

  38. Dikshit RP, Kanhere S. Tobacco habits and risk of lung, oropharyngeal and oral cavity cancer: a population-based case-control study in Bhopal, India. Int J Epidemiol. 2000;29:609–14.

    CAS  PubMed  Google Scholar 

  39. Goud ML, Mohapatra SC, Mohapatra P, Gaur SD, Pant GC, Knanna MN. Epidemiological correlates between consumption of Indian chewing tobacco and oral cancer. Eur J Epidemiol. 1990;6:219–22.

    CAS  PubMed  Google Scholar 

  40. Jayalekshmi PA, Gangadharan P, Akiba S, Nair RRK, Tsuji M, Rajan B. Tobacco chewing and female oral cavity cancer risk in Karunagappally cohort, India. Br J Cancer. 2009;100:848–52.

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Jayalekshmi PA, Gangadharan P, Akiba S, Koriyama C, Nair RRK. Oral cavity cancer risk in relation to tobacco chewing and bidi smoking among men in Karunagappally, Kerala, India: Karunagappally cohort study. Cancer Sci. 2011;102:460–7.

    CAS  PubMed  Google Scholar 

  42. Jayant K, Balakrishnan V, Sanghvi LD, Jussawalla DJ. Quantification of the role of smoking and chewing tobacco in oral, pharyngeal, and oesophageal cancers. Br J Cancer. 1977;35:232–5.

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Jussawalla DJ, Deshpande VA. Evaluation of cancer risk in tobacco chewers and smokers: an epidemiologic assessment. Cancer. 1971;28:244–52.

    CAS  PubMed  Google Scholar 

  44. Madani AH, Jahromi AS, Madhurima D, Debanshu B, et al. Risk assessment of tobacco types and oral cancer. Am J Pharmacol Toxicol. 2010;5:9–13.

    Google Scholar 

  45. Muwonge R, Ramadas K, Sankila R, Thara S, Thomas G, Vinoda J, et al. Role of tobacco smoking, chewing and alcohol drinking in the risk of oral cancer in Trivandrum, India: a nested case-control design using incident cancer cases. Oral Oncol. 2008;44:446–54.

    CAS  PubMed  Google Scholar 

  46. Nandakumar A, Thimmasetty KT, Sreeramareddy NM, Venugopal TC, Rajanna, Vinutha AT, et al. A population-based case-control investigation on cancers of the oral cavity in Bangalore, India. Br J Cancer. 1990;62:847–51.

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Rao DN, Ganesh B, Rao RS, Desai PB. Risk assessment of tobacco, alcohol and diet in oral cancer—a case-control study. Int J Cancer. 1994;58:469–73.

    CAS  PubMed  Google Scholar 

  48. Sanghvi LD, Rao KC, Khanolkar VR. Smoking and chewing of tobacco in relation to cancer of the upper alimentary tract. Br Med J. 1955;1:1111–4.

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Sankaranarayanan R, Duffy SW, Padmakumary G, Day NE, Krishan NM. Risk factors for cancer of the buccal and labial mucosa in Kerala, southern India. J Epidemiol Community Health. 1990;44:286–92.

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Wasnik KS, Ughade SN, Zodpey SP, Ingole DL. Tobacco consumption practices and risk of oro-pharyngeal cancer: a case-control study in Central India. Southeast Asian J Trop Med Public Health. 1998;29:827–34.

    CAS  PubMed  Google Scholar 

  51. Subapriya R, Thangavelu A, Mathavan B, Ramachandran CR, Nagini S. Assessment of risk factors for oral squamous cell carcinoma in Chidambaram, Southern India: a case–control study. Eur J Cancer Prev. 2007;16:251.

    PubMed  Google Scholar 

  52. Wahi PN, Kehar U, Lahiri B. Factors influencing oral and oropharyngeal cancers in India. Br J Cancer. 1965;19:642–60.

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Merchant A, Husain SS, Hosain M, Fikree FF, Pitiphat W, Siddiqui AR, et al. Paan without tobacco: an independent risk factor for oral cancer. Int J Cancer. 2000;86:128–31.

    CAS  PubMed  Google Scholar 

  54. Roosaar A, Johansson ALV, Sandborgh-Englund G, Axéll T, Nyrén O. Cancer and mortality among users and nonusers of snus. Int J Cancer. 2008;123:168–73.

    CAS  PubMed  Google Scholar 

  55. Znaor A, Brennan P, Gajalakshmi V, Mathew A, Shanta V, Varghese C, et al. Independent and combined effects of tobacco smoking, chewing and alcohol drinking on the risk of oral, pharyngeal and esophageal cancers in Indian men. Int J Cancer. 2003;105:681–6.

    CAS  PubMed  Google Scholar 

  56. Boffetta P, Aagnes B, Weiderpass E, Andersen A. Smokeless tobacco use and risk of cancer of the pancreas and other organs. Int J Cancer. 2005;114:992–5.

    CAS  PubMed  Google Scholar 

  57. Lewin F, Norell SE, Johansson H, Gustavsson P, Wennerberg J, Biörklund A, et al. Smoking tobacco, oral snuff, and alcohol in the etiology of squamous cell carcinoma of the head and neck: a population-based case-referent study in Sweden. Cancer. 1998;82:1367–75.

    CAS  PubMed  Google Scholar 

  58. Luo J, Ye W, Zendehdel K, Adami J, Adami H-O, Boffetta P, et al. Oral use of Swedish moist snuff (snus) and risk for cancer of the mouth, lung, and pancreas in male construction workers: a retrospective cohort study. Lancet. 2007;369:2015–20.

    PubMed  Google Scholar 

  59. Rosenquist K, Wennerberg J, Schildt E-B, Bladström A, Hansson BG, Andersson G. Use of Swedish moist snuff, smoking and alcohol consumption in the aetiology of oral and oropharyngeal squamous cell carcinoma. A population-based case-control study in southern Sweden. Acta Otolaryngol. 2005;125:991–8.

    PubMed  Google Scholar 

  60. Schildt E-B, Eriksson M, Hardell L, Magnuson A. Oral snuff, smoking habits and alcohol consumption in relation to oral cancer in a Swedish case-control study. Int J Cancer. 1998;77:341–6.

    CAS  PubMed  Google Scholar 

  61. Mashberg A, Boffetta P, Winkelman R, Garfinkel L. Tobacco smoking, alcohol drinking, and cancer of the oral cavity and oropharynx among U.S. veterans. Cancer. 1993;72:1369–75.

    CAS  PubMed  Google Scholar 

  62. Sapkota A, Gajalakshmi V, Jetly DH, Roychowdhury S, Dikshit RP, Brennan P, et al. Smokeless tobacco and increased risk of hypopharyngeal and laryngeal cancers: a multicentric case–control study from India. Int J Cancer. 2007;121:1793–8.

    CAS  PubMed  Google Scholar 

  63. Akhtar S, Sheikh AA, Qureshi HU. Chewing areca nut, betel quid, oral snuff, cigarette smoking and the risk of oesophageal squamous-cell carcinoma in South Asians: a multicentre case–control study. Eur J Cancer. 2012;48:655–61.

    PubMed  Google Scholar 

  64. Dar NA, Bhat GA, Shah IA, Iqbal B, Makhdoomi MA, Nisar I, et al. Hookah smoking, nass chewing, and oesophageal squamous cell carcinoma in Kashmir, India. Br J Cancer. 2012;107:1618–23.

    CAS  PubMed  PubMed Central  Google Scholar 

  65. Sehgal S, Kaul S, Gupta BB, Dhar MK. Risk factors and survival analysis of the esophageal cancer in the population of Jammu, India. Indian J Cancer. 2012;49:245–50.

    CAS  PubMed  Google Scholar 

  66. Talukdar FR, Ghosh SK, Laskar RS, Mondal R. Epigenetic, genetic and environmental interactions in esophageal squamous cell carcinoma from northeast India. PLoS One. 2013;8:e60996.

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Lagergren J, Bergström R, Lindgren A, Nyrén O. The role of tobacco, snuff and alcohol use in the aetiology of cancer of the oesophagus and gastric cardia. Int J Cancer. 2000;85:340–6.

    CAS  PubMed  Google Scholar 

  68. Zendehdel K, Nyrén O, Luo J, Dickman PW, Boffetta P, Englund A, et al. Risk of gastroesophageal cancer among smokers and users of Scandinavian moist snuff. Int J Cancer. 2008;122:1095–9.

    CAS  PubMed  Google Scholar 

  69. Bolinder G, Alfredsson L, Englund A, de Faire U. Smokeless tobacco use and increased cardiovascular mortality among Swedish construction workers. Am J Public Health. 1994;84:399–404.

    CAS  PubMed  PubMed Central  Google Scholar 

  70. Sasco AJ, Merrill RM, Dari I, Benhaïm-Luzon V, Carriot F, Cann CI, et al. A case--control study of lung cancer in Casablanca, Morocco. Cancer Causes Control. 2002;13:609–16.

    PubMed  Google Scholar 

  71. Brown LM, Blot WJ, Schuman SH, Smith VM, Ershow AG, Marks RD, et al. Environmental factors and high risk of esophageal cancer among men in coastal South Carolina. J Natl Cancer Inst. 1988;80:1620–5.

    CAS  PubMed  Google Scholar 

  72. Alguacil J, Silverman DT. Smokeless and other noncigarette tobacco use and pancreatic cancer: a case-control study based on direct interviews. Cancer Epidemiol Biomark Prev. 2004;13:55–8.

    CAS  Google Scholar 

  73. Hassan MM, Abbruzzese JL, Bondy ML, Wolff RA, Vauthey J-N, Pisters PW, et al. Passive smoking and the use of noncigarette tobacco products in association with risk for pancreatic cancer: a case-control study. Cancer. 2007;109:2547–56.

    PubMed  PubMed Central  Google Scholar 

  74. Khan Z, Dreger S, Shah SMH, Pohlabeln H, Khan S, Ullah Z, et al. Oral cancer via the bargain bin: the risk of oral cancer associated with a smokeless tobacco product (Naswar). PLoS One. 2017;12:e0180445.

    PubMed  PubMed Central  Google Scholar 

  75. Mahapatra S, Kamath R, Shetty BK, Binu VS. Risk of oral cancer associated with gutka and other tobacco products: a hospital-based case-control study. J Cancer Res Ther. 2015;11:199–203.

    CAS  PubMed  Google Scholar 

  76. Merchant AT, Pitiphat W. Total, direct, and indirect effects of paan on oral cancer. Cancer Causes Control. 2015;26:487–91.

    PubMed  Google Scholar 

  77. Alexander M. Tobacco use and the risk of cardiovascular diseases in developed and developing countries. University of Cambridge; 2013. https://www.repository.cam.ac.uk/handle/1810/245058..

  78. Rahman MA, Zaman MM. Smoking and smokeless tobacco consumption: possible risk factors for coronary heart disease among young patients attending a tertiary care cardiac hospital in Bangladesh. Public Health. 2008;122:1331–8.

    CAS  PubMed  Google Scholar 

  79. Rahman MA, Spurrier N, Mahmood MA, Rahman M, Choudhury SR, Leeder S. Is there any association between use of smokeless tobacco products and coronary heart disease in Bangladesh? PLoS One. 2012;7:e30584.

    CAS  PubMed  PubMed Central  Google Scholar 

  80. Agashe A, Gawde N. Stroke and the use of smokeless tobacco--a case-control study. Healthline. 2013;4:13–8.

    Google Scholar 

  81. Huhtasaari F, Asplund K, Lundberg V, Stegmayr B, Wester PO. Tobacco and myocardial infarction: is snuff less dangerous than cigarettes? BMJ. 1992;305:1252–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  82. Huhtasaari F, Lundberg V, Eliasson M, Janlert U, Asplund K. Smokeless tobacco as a possible risk factor for myocardial infarction: a population-based study in middle-aged men. J Am Coll Cardiol. 1999;34:1784–90.

    CAS  PubMed  Google Scholar 

  83. Asplund K, Nasic S, Janlert U, Stegmayr B. Smokeless tobacco as a possible risk factor for stroke in men: a nested case-control study. Stroke. 2003;34:1754–9.

    PubMed  Google Scholar 

  84. Hergens M-P, Ahlbom A, Andersson T, Pershagen G. Swedish moist snuff and myocardial infarction among men. Epidemiology. 2005;16:12–6.

    PubMed  Google Scholar 

  85. Haglund B, Eliasson M, Stenbeck M, Rosén M. Is moist snuff use associated with excess risk of IHD or stroke? A longitudinal follow-up of snuff users in Sweden. Scand J Public Health. 2007;35:618–22.

    PubMed  Google Scholar 

  86. Hergens M-P, Alfredsson L, Bolinder G, Lambe M, Pershagen G, Ye W. Long-term use of Swedish moist snuff and the risk of myocardial infarction amongst men. J Intern Med. 2007;262:351–9.

    PubMed  Google Scholar 

  87. Wennberg P, Eliasson M, Hallmans G, Johansson L, Boman K, Jansson J-H. The risk of myocardial infarction and sudden cardiac death amongst snuff users with or without a previous history of smoking. J Intern Med. 2007;262:360–7.

    CAS  PubMed  Google Scholar 

  88. Hergens M-P, Lambe M, Pershagen G, Terent A, Ye W. Smokeless tobacco and the risk of stroke. Epidemiology. 2008;19:794–9.

    PubMed  Google Scholar 

  89. Hansson J, Pedersen NL, Galanti MR, Andersson T, Ahlbom A, Hallqvist J, et al. Use of snus and risk for cardiovascular disease: results from the Swedish Twin Registry. J Intern Med. 2009;265:717–24.

    CAS  PubMed  Google Scholar 

  90. Janzon E, Hedblad B. Swedish snuff and incidence of cardiovascular disease. A population-based cohort study BMC Cardiovasc Disord. 2009;9:21.

    PubMed  Google Scholar 

  91. GBD Results Tool | GHDx. http://ghdx.healthdata.org/gbd-results-tool. Accessed 6 Apr 2020. Accessed 6 Apr 2020.

  92. Singh PK, Yadav A, Lal P, Sinha DN, Gupta PC, Swasticharan L, et al. Dual burden of smoked and smokeless tobacco use in India, 2009–2017: a repeated cross-sectional analysis based on global adult tobacco survey. Nicotine Tobacco Research. 2020. https://0-doi-org.brum.beds.ac.uk/10.1093/ntr/ntaa033.

  93. Mehrotra R, Yadav A, Sinha DN, Parascandola M, John RM, Ayo-Yusuf O, et al. Smokeless tobacco control in 180 countries across the globe: call to action for full implementation of WHO FCTC measures. Lancet Oncol. 2019;20:e208–17.

    PubMed  Google Scholar 

  94. Siddiqi K, Islam Z, Khan Z, Siddiqui F, Mishu M, Dogar O, et al. Identification of policy priorities to address the burden of smokeless tobacco in Pakistan: a multimethod analysis. Nicotine Tob Res. 2019. https://0-doi-org.brum.beds.ac.uk/10.1093/ntr/ntz163.

  95. Mehrotra R, Kaushik N, Kaushik R. Why smokeless tobacco control needs to be strengthened? Cancer Control. 2020;27:1073274820914659.

    PubMed  PubMed Central  Google Scholar 

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Funding

This study was funded by the National Institute for Health Research by a Grant No: 17/63/76 to support a Global Health Research Group on Addressing Smokeless Tobacco and building Research capacity in south Asia (ASTRA).

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KS jointly developed the study idea, planned the analysis, interpreted the findings, wrote the methods, results and discussion sections and approved the final manuscript. SH led two literature reviews, interpreted the findings, contributed to the tables and approved the final manuscript.

AV led one of the literature reviews, interpreted the findings, drafted several tables and approved the final manuscript. AR contributed to the literature reviews, interpreted the findings, wrote the background section and approved the final manuscript. MM contributed to the literature reviews, interpreted the findings, reviewed the analysis and the tables and approved the final manuscript. AS jointly developed the study idea, interpreted the findings, critically reviewed the write up and approved the final manuscript.

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Correspondence to Kamran Siddiqi.

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Additional file 1.

Supplementary description of methods and results sections.

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Siddiqi, K., Husain, S., Vidyasagaran, A. et al. Global burden of disease due to smokeless tobacco consumption in adults: an updated analysis of data from 127 countries. BMC Med 18, 222 (2020). https://0-doi-org.brum.beds.ac.uk/10.1186/s12916-020-01677-9

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