Table 4 Summary of studies, level of evidence, and quality for health outcomes from SLT by region

Global

Mortality

 Gupta [10]

14 studies

IHD Mortality, stroke

Fatal stroke: OR = 1.27; 95% CI 1.15–1.39

3A

Poor

 Siddiqi [13]

32 studies

DALYs and mortality

1.7 million, DALYs lost and 62,283 deaths due to cancers of mouth, pharynx and oesophagus

3A

Poor

 Sinha [12]

16 studies

Mortality due to all cause, cancer mortality

All-cause mortality: OR = 1.33; 95% CI 1.11–1.34

All cancer mortality: OR = 1.31; 95% CI 1.16–1.47

IHD mortality: OR = 1.10; 95% CI 1.04–1.17

Stroke mortality: OR = 1.37; 95% CI 1.24–1.51

3A

Poor

 Vidyasagaran [11]

19 studies

IHD mortality, stroke mortality

IHD deaths: OR = 1.15; 95% CI 1.01–1.30

Stroke deaths: OR = 1.39; 95% CI 1.29–1.49

3A

Good

Morbidity

Cancer

 Asthana [52]

37 studies

Oral cancer

Oral cancer: OR = 3.52; 95% CI 2.75–4.51

3A

Poor

 Siddiqi [13]

32 studies

Oral, pharyngeal, esophageal cancers

Mouth cancers: OR = 3.43; 95% CI 2.26–5.19

Pharynx cancer: OR = 2.23; 95% CI 1.55–3.20

Esophageal cancers: OR = 2.17; 95% CI 1.70–2.78

3A

Poor

Cardiovascular

 Gupta [10]

14 studies

IHD Mortality, stroke

Stroke: OR = 1.18; 95% CI 1.04–1.32

Fatal stroke: OR = 1.27; 95% CI 1.15–1.39

Nonfatal stroke: OR = 1.03; 95% CI 0.91–1.14

3A

Poor

 Gupta [9]

20 studies

CHD

CHD: OR = 1.05; 95% CI 0.96–1.15

2A

Good

 Vidyasagaran [11]

19 studies

IHD

IHD: OR = 1.14; 95% CI 0.92–1.42

Stroke: OR = 1.01; 95% CI 0.90–1.13

3A

Good

AMEA

Mortality

 Etemadi [14]

50,045

Overall mortality, IHD mortality, CVA mortality, cancer mortality

Mortality: HR = 1.16; 95% CI 1.01–1.34

Cancer mortality: HR = 1.40; 95% CI 1.01–1.95

IHD mortality: HR = 1.32; 95% CI 1.05–1.67

CVA mortality: HR = 1.06; 95% CI 0.74–1.53

Respiratory mortality: HR = 1.73; 95% CI 0.94–3.19

2B

Fair

 Gupta [10]

14 studies

IHD mortality, stroke

Fatal stroke: OR = 1.35; 95% CI 1.18–1.51

3A

Poor

 Sinha [12]

16 studies

Mortality, all cancer, UADT cancer, stomach cancer, cervical cancer, IHD, stroke

All-cause mortality: OR = 1.25; 95% CI 1.08–1.44

All cancer mortality: OR = 1.46; 95% CI 1.26–1.68

Stroke mortality: OR = 1.37; 95% CI 1.14–1.64

3A

Poor

 Vidyasagaran [11]

19 studies

IHD

IHD mortality: OR = 1.05; 95% CI .076–1.47

3A

Good

 Gajalakshmi [15]

22,460 cases, 429,306 controls

All-cause mortality, cancer deaths, respiratory deaths, stroke deaths (verbal autopsy)

All-cause mortality: RR = 1.3; 95% CI 1.2–1.4

Respiratory diseases combined: RR = 1.5; 95% CI 1.4–1.7

Respiratory tuberculosis: RR = 1.7; 95% CI 1.5–1.9

Cancers (all sites combined): RR = 1.5; 95% CI 1.4–1.7

Stroke: RR = 1.4; 95% CI 1.2–1.6

3B

Poor

Morbidity

Cancer

 Gholap [34]

Ecological analysis

Head and neck cancer

(r = 0.53) oropharynx cancer incidence

2C

Fair

 Nair [32]

747

Squamous cell carcinoma

No HR/OR reported

2C

Poor

 Asthana [52]

37 studies

Oral cancer

Oral cancer in Southeast Asia: OR = 4.44; 95% CI 3.51–5.61

Oral cancer in Eastern Mediterranean:OR = 1.28; 95% CI 1.04–1.56

3A

Poor

 Khan [20]

6 studies

Squamous cell carcinoma

Oral cancer: OR = 11.8; 95% CI 11.4–25.3; I2 = 67%

3A

Good

 Prasad [78]

22 studies

Six cancers

Oral cancer: OR = 6.6 (95% CI 5.2–8.4)

Larynx: cancer OR = 1.42 (95% CI 0.69–2.90)

Lung cancer: OR = 2.15 (95% CI 1.22–3.78)

Esophagus cancer: OR = 3.46 (95% CI 1.95–5.72)

Oropharynx cancer: not significant

Hypopharynx cancer: not significant

3A

Fair

 Quadri [22]

6 studies

Oral cancer

Oral cancer: OR = 38.74; 95% CI 19.50–76.96

3A

Poor

 Siddiqi [13]

32 studies

Oral, pharyngeal, oesophageal cancers

Mouth cancers in India: OR = 5.12; 95% CI 3.27–8.02

Mount cancers in Pakistan: OR = 8.81; 95% CI 3.14–24.69

Pharynx cancer in India: OR = 2.60; 95% CI 1.76–3.85

Oesophageal cancers in India: OR = 2.57; 95% CI 2.20–3.00

Oesophageal cancers in Pakistan: OR = 8.20; 95% CI 1.45–27.47

3A

Poor

Sinha [21]

25 studies

Cancers

Oral cancer: OR = 5.67; 95% CI 3.83–8.40

Pharyngeal cancer: OR = 2.69; 95% CI 2.28–3.17

Oesophageal cancer: OR = 3.17; 95% CI 2.76–3.63

3A

Poor

 Alharbi [24]

70 cases, 140 controls

Squamous cell carcinoma of oral cavity

Shammah: OR = 33.01; 95% CI 3.22–39.88

Shisha: OR = 3.96; 95% CI 0.24–63

Shammah and shisha: OR = 35.03; 95% CI 11.50–65.66

3B

Poor

 Awan [25]

134 cases, 134 controls

Oral cancer

Gutka: OR = 5.54; 95% CI 2.83–10.83; p < 0.001

Chewing tobacco: OR = 5.32; 95% CI 1.14–24.77; p = 0.033

3B

Fair

 Chang [35]

549 cases, 601 controls

Oral cavity, oropharynx, hypopharynx and larynx cancers

Head and neck cancer: OR = 2.39; 95% CI 1.77–3.23

3B

Fair

Gupta [26]

187 cases, 240 controls

Squamous cell carcinoma

OR = 8.51; 95% CI 4.90–14.77

3B

Fair

 Hassanin [27]

196

Oral squamous cell carcinoma

OR = 3.8; 95% CI 1.7–8.6

3B

Poor

 Kadashetti [30]

100 cases, 100 controls

Oral cancer

OR = 2.8; 95% CI 1.2–7.0

3B

Fair

 Khan [28]

84 cases, 174 controls

Oral cancer

OR = 21.0; 95% CI 6.1–72

3B

Poor

 Khan [31]

90 cases, 120 controls

Oral cavity cancer

OR = 4.71; 95% CI 2.53–8.74

3B

Poor

 Merchant [79]

79 cases, 143 controls

Oral squamous cell carcinoma

OR = 7.39; 95% CI 1.01–38.11

3B

Fair

 Mohite [37]

217 cases, 217 controls

Breast cancer

OR = 2.35; 95% CI 1.01–5.51

3B

Poor

 Nair [39]

100 cases, 200 controls

Colorectal cancer

OR = 1.53; 95% CI 0.58–4.0

3B

Poor

 Quadri [23]

48 cases, 96 controls

Oral cancer

OR = 29.30; 95% CI 10.33–83.13

3B

Fair

 Rajbongshi [36]

100 cases, 100 controls

Breast cancer

OR = 2.35; 95% CI 1.3–4.15

3B

Poor

 Shah [38]

70 cases, 140 controls

Gastric cancer

OR = 4.37; 95% CI 1.92–9.95

3B

Fair

 Sajad[80]

35 year-old male

Squamous cell carcinoma

OSCC in buccal mucosa and the reason for the same was exclusive unilateral tobacco chewing habit, with placement of the tobacco in the right mucobuccal fold

4

Fair

 Mahapatra [29]

134 cases, 268 controls

oral cancer

OR = 6.0; 95% CI 2.6–15.5

4

Poor

 Soni [33]

100 cases

oral cancer

Significant difference in oral cancer among patients who exclusively chewed tobacco than non-users of tobacco

4

Poor

Cardiovascular

 Gupta [9]

20 studies

CHD

CHD: OR = 1.02; 95% CI 0.86–1

Non-fatal CHD: OR = 1.10; 95% CI 1.00–1.20

Fatal CHD: OR = 1.03; 95% CI 0.86–1.19

2A

Good

 Ahwal [19]

90

Hypertension, blood fasting blood glucose, diabetes, dyslipidemia

Dyslipidemia: OR = 6.37; 95% CI 1.4–27.3

Hypertension: OR = 6.97; 95% CI 1.7–28.0

2C

Poor

 Anand [17]

4038

Diabetes, asthma, hypertension

Risk of diabetes and hypertension not statistically significant among self-reported exclusive SLT users compared to exclusive smokers

2C

Fair

 Bhatt[81]

314

Systolic BP, diastolic BP

Systolic hypertension associated with quantity of SLT use (B = 0.389 (SE = 0.131); p = 0.003), but diastolic hypertension was not (B = 0.122 (SE = 0.087); p = 0.160)

2C

Good

 Mishra [18]

36

Latent CHD

No difference in CHD between those who exclusively smoke and those who use exclusive SLT

2C

Poor

 Gupta [10]

14 studies

IHD Mortality, stroke

Strok: OR = 1.35; 95% CI 1.18–1.51

Fatal stroke: OR = 1.35; 95% CI 1.18–1.51

3A

Poor

 Vidyasagaran [11]

19 studies

IHD

IHD: OR = 1.40; 95% CI 1.01–1.95

IHD death: OR = 1.05; 95% CI .076–1.47

3A

Good

 Behera [16]

423

stroke and MI

Stroke: OR = 3.71; 95% CI 1.57–9.05

MI: OR = 2.34; 95% CI 1.10–5.40

4

Poor

Other

 Anand [17]

4038

Diabetes, asthma, hypertension, chronic lung disease

Chronic lung disease: OR = 0.64; 95% CI 0.45–0.91

2C

Fair

 Ahwal [19]

90

Hypertension, blood glucose, diabetes, dyslipidemia

There was no difference in the prevalence of obesity (BMI >  = 25) among SLT users, smokers and non-tobacco users (p = 0.393)

2C

Poor

 Mahapatra [29]

512

Oral health

Gingival bleeding: OR = 1.710; 95% CI 1.2–2.43

Periodontal pockets: OR = 1.715; 95% CI 1.19–2.48

Loss of attachment: OR = 2.393; 95% CI 1.55–3.69

2C

Fair

 Mathew [82]

800

Reproductive health

Obstetrical problems: OR = 4.1; 95% CI 2.54–6.64

Neonatal problems: OR = 2.78; 95% CI 1.59–4.87

2C

Poor

US

Mortality

 Fisher [41]

210,090 and 154,286

All-cause and disease-specific (cancer, cardiovascular) mortality

Mortality (NHIS): HR = 1.03; 95% CI .83–1.29; (NLMS): HR = 0.82; 95% CI 0.59–1.13)

Malignant neoplasms of:

 Trachea, bronchus, and lung: HR = 2.98; 95% CI 0.91–9.76

 Digestive organs: HR = 1.01; 95% CI 0.32–3.20

 Esophagus: HR = 2.44; 95% CI .31–19.1

 Pancreas: HR = 1.36; 95% CI .19–9.98

 Ggenitourinary system: HR = 0.51; 95% CI 0.007–3.78

Heart disease (NLMS): HR = 1.07; 95% CI 0.65–1.75; (NHIS): HR = 1.20; 95% CI 0.91–1.58

Heart failure (NLMS): HR = 1.13; 95% CI 0.28–4.62; (NHIS): HR = 2.75; 95% CI 1.55–4.89

IHD (NLMS): HR = 0.95; 95% CI 0.49–1.83; (NHIS): HR = 1.06; 95% CI 0.75–1.49

2A

Good

 Inoue-Choi [45]

65,335

Cancer-specific mortality

Mortality: HR = 1.36; 95% CI 1.17–1.59

CHD mortality: HR = 1.63; 95% CI 1.27–2.09

Cancer mortality: HR = 1.48; 95% CI 1.04–2.12

Smoking-related cancer mortality: HR = 1.76; 95% CI 1.07–2.90

2B

Good

 Rodu [43]

46,104

Mortality

Younger (40–59 years)/all-cause mortality: HR = 1.44; 95% CI 1.12–1.84

2B

Good

 Timberlake [44]

349,282

Mortality from all causes, all cancers, CHD, cerebrovascular disease and digestive system cancers

All-cause mortality: HR = 1.01; 95% CI 0.93–1.10

All cancers: HR = 0.99; 95% CI 0.82–1.21

Cerebrovascular disease: HR = 0.92; 95% CI 0.67–1.27

Death from CHD: HR = 1.25; 95% CI 1.05–1.46

2B

Fair

 Sinha [12]

16 studies

Mortality due to all cause, all cancer, UADT cancer, stomach cancer, cervical cancer, IHD, stroke

All-cause mortality: OR = 1.17; 95% CI 1.12–1.22

All cancer mortality: OR = 1.14; 95% CI 1.01–1.29

Stroke mortality: OR = 1.44; 95% CI 1.30–1.59

IHD mortality: OR = 1.16; 95% CI 1.05–1.28

3A

Poor

 Vidyasagaran [11]

19 studies

IHD

IHD death: OR = 1.03; 95% CI 0.83–1.27

3A

Good

Morbidity

Cancer

 Asthana [52]

37 studies

Oral cancer

OR = 4.72; 95% CI 0.66–33.62

3A

Poor

 Siddiqi [13]

32 studies

Oral, pharyngeal, oesophageal cancers

Mouth cancers: OR = 0.95; 95% CI 0.7–1.2

Pharynx cancer: OR = 1.59; 95% CI 0.84–3.01

Oesophageal cancers: OR = 1.20; 95% CI 0.10–14.40

3A

Poor

 Wyss [48]

6772 cases, 8375 controls

oral, pharyngeal, and laryngeal cancers

Head and neck cancer (HNC): OR = 1.71; 95% CI 1.08–2.70

3A

Poor

Cardiovascular

 Gupta [9]

20 studies

CHD

OR = 1.04; 95% CI 0.83–1.24

2A

Good

 Obisesan [47]

13,086

Hypertension

Odds of hypertension: 0.88 times lower (95% CI 0.7907–0.9896)

2C

Fair

 Gupta [10]

14 studies

IHD Mortality, stroke

Stroke: OR = 1.21; 95% CI 0.90–1.51

Fatal stroke: OR = 1.21; 95% CI 0.90–1.51

3A

Poor

 Rostron [46]

24 studies

IHD, stroke

IHD: RR = 1.17; 95% CI 1.08–1.27

Stroke: RR = 1.28; 95% CI 1.01–1.62

3A

Good

Other

 Hernandez [41]

4930

Self-reported chronic health conditions

At least one chronic health condition: OR = 1.49; 95% CI 1.23–1.81

2C

Poor

 King [49]

2370

Self-reported depression, stress, mental health diagnosis

Mental health diagnosis: AOR = 1.16; 95% CI 0.64–2.10; p = 0.594 Depression: AOR = 0.98; 95% CI 0.95–1.00

Stress: AOR = 1.03; 95% CI 1.00–1.05

2C

Fair

Europe

Mortality

 Araghi [50]

417,872

All-cause mortality, colorectal cancer

All-cause mortality: HR = 1.16; 95% CI 0.89, 1.50

2A

Fair

 Wilson [51]

9582

Prostate cancer mortality, overall mortality

Overall mortality: HR = 1.19; 95% CI 1.04–1.37

Prostate cancer-specific mortality: HR = 1.24; 95% CI 1.03–1.49

2B

Fair

 Gupta [10]

of 14 studies

IHD Mortality, stroke

Fatal stroke: OR = 1.30; 95% CI 0.96–1.63

3A

Poor

 Sinha [12]

16 studies

Mortality, all cancer, UADT cancer, stomach cancer, cervical cancer, IHD, stroke

IHD mortality: OR = 1.16; 95% CI 1.05–1.28

3A

Poor

 Vidyasagaran [11]

19 studies

IHD

IHD death: OR = 1.38; 95% CI 1.13–1.67

Stroke death: OR = 1.28; 95% CI 0.98–1.68

3A

Good

Morbidity

Cancer

 Araghi [50]

417,872

Colorectal cancer, all–cause mortality, cancer-specific mortality

Colorectal cancer: HR = 1.22; 95% CI 0.91, 1.64

Colon cancer: HR = 1.02; 95% CI 0.81–1.29

Rectal cancer: HR = 1.29; 95% CI 1.02–1.30

2A

Fair

 Araghi [53]

418,488

Pancreatic cancer

HR = 0.96; 95% CI 0.83–1.11

2A

Fair

 Asthana [52]

37 studies

Oral cancer

OR = 0.86; 95% CI 0.58–1.29

3A

Poor

 Siddiqi [13]

32

Oral, pharyngeal, oesophageal cancers

Mouth (oral cavity, tongue, and lip) cancers: Sweden: OR = 0.92; 95% CI 0.68–1.25; Norway: OR = 1.10; 95% CI 0.5–2.42

Pharynx cancer: Sweden: OR = 1.45; 95% CI 0.3–6.21

Oesophageal cancers: Norway: OR = 1.40; 95% CI 1.61–3.21; Sweden: OR = 1.26; 95% CI 1.02–1.56

3A

Poor

Cardiovascular

 Gupta [9]

20 studies

CHD

OR = 0.95; 95% CI 0.86–1.04

2A

Good

 Gupta [10]

14 studies

IHD Mortality, stroke

Stroke: OR = 1.04; 95% CI 0.94–1.15

Fatal stroke: OR = 1.30; 95% CI CHD-1.63

3A

Poor

 Rostron [46]

24 studies

IHD, stroke

IHD: RR = 1.04; 95% CI 0.93–1.16

Stroke: RR = 1.04; 95% CI 0.92–1.17

3A

Good

 Vidyasagaran [11]

19 studies

IHD

IHD: OR = 0.91; 95% CI 0.83–1.01

Stroke: OR = 1.01; 95% CI .90–1.13

3A

Good

Other

 Rauwolf [83]

347

Alcohol dependence

No significant differences between the four groups regarding total abstinence (i.e. no alcohol consumption after end of treatment), days of alcohol consumption the last 30 days or grams of pure alcohol per week

2B

Fair

 Yang [54]

348,601

Parkinson’s

60% lower Parkinson’s disease risk/HR = 0.41; 95% CI 0.28–0.61

2A

Good

 Gudnadóttir [55]

16,082

Asthma, respiratory symptoms, sleep-related problems

Asthma: OR = 1.49; 95% CI 1.20–1.85

Chronic bronchitis: OR = 1.47; 95% CI 1.21–1.78

Chronic rhinosinusitis: OR = 1.37; 95% CI 1.11–1.70

2C

Good