Aberrant glycosylation of secretory mucin from the oral cavity in tobacco consumers: a pilot study.

Mucins are a family of high-molecular-weight O-linked glycoproteins which are the primary structural components of mucus and maintain homeostasis in the oral cavity. The present study was conducted as the first step towards establishing a correlation of aberrant mucin glycosylation with tobacco-associated clinical conditions. Tobacco habituates for the study were identified on the basis of type, duration, amount, and frequency of using tobacco products. The secretory mucin and its saccharides were determined from the saliva collected from smokers, smokeless tobacco habituates, and healthy, nonsmoking individuals. On the one hand, the salivary mucin content was markedly reduced in smokeless tobacco habituates with respect to smokers. On the other hand, the amount of sialic acid and fucose moieties of salivary mucin was increased in both smokers and smokeless tobacco habituates compared to the healthy cohort. Furthermore, the duration of tobacco exposure have been identified as the main factor influencing the extent of damage to the oral mucosa in terms of mucin secretion. The reduced secretory mucin content with aberrant glycosylation in the oral cavity may have a significant role in the further development or progression of oral diseases.

Use patterns of flavored non-cigarette tobacco products among US adults, 2010-2019.

OBJECTIVE: Flavored non-cigarette tobacco product (NCTP) use is common among US adult tobacco users. To update the estimates of use patterns of flavored NCTPs, this study assessed current NCTP use among adults by flavor use and flavor categories from 2010 to 2019. METHODS: We analyzed data from the 2010-2019 Tobacco Use Supplement to the Current Population Survey to estimate the weighted proportion of adult NCTP users by flavor use across survey waves. Flavor use was defined as past 30-day use of any menthol/mint or fruit/other flavors. We used the 2018-2019 data to examine the differences in demographic characteristics and tobacco use patterns among users of menthol/mint or fruit/other flavors compared to exclusive users of tobacco flavor, by product type. RESULTS: Compared to 2014-2015, electronic nicotine delivery system (ENDS) users were more likely (79.0% vs. 66.6%, p < 0.001) to report flavor use in 2018-2019, whereas cigar (26.9% vs. 31.2%, p = 0.030) and pipe (56.3% vs. 65.5%, p = 0.015) smokers were less likely to report flavor use in 2018-2019. In 2018-2019, the most prevalent flavor categories were exclusive use of tobacco flavor among cigar (73.1%) and smokeless tobacco (48.3%) users, and use of fruit/other flavors among ENDS (64.9%) and pipe (48.4%) users. Flavored users were more likely to be young adults aged 18-24 years (cigars, ENDS, smokeless tobacco) and Non-Hispanic Black or Hispanic persons (cigars, ENDS, pipes) compared to tobacco-flavored users. CONCLUSIONS: Flavored product use increased among adult ENDS users but decreased among cigar and pipe smokers. These findings could inform tobacco regulatory efforts concerning flavored NCTPs.

Urinary anatalline and nicotelline cut-points to distinguish between exclusive and dual use of tobacco products.

OBJECTIVE: This study measured anatalline and nicotelline, two minor tobacco alkaloids, to discriminate between exclusive smokeless tobacco (SLT) use, exclusive electronic nicotine delivery systems (ENDS) use, exclusive cigarette use, dual SLT and cigarette use, and dual ENDS and cigarette use. METHODS: N = 664 urine samples from participants in the Population Assessment of Tobacco and Health Study were analyzed for anatalline and nicotelline. Geometric means and 95% confidence intervals were calculated for biomarker levels and their ratios. Non-parametric Receiver Operating Characteristic analyses were used to determine optimal cut-points of natural log-transformed biomarker ratios for distinguishing between tobacco use groups. RESULTS: The anatalline/nicotelline ratio distinguished exclusive cigarette from exclusive SLT use (threshold = 18.1, sensitivity = 89.3%, specificity = 86.4%, AUC = 0.90), and exclusive SLT from exclusive ENDS use (threshold = 12.8, sensitivity = 96.4%, specificity = 76.3%, AUC = 0.90) very well, but had reduced sensitivity and specificity when distinguishing exclusive cigarette from exclusive ENDS or any dual use with cigarettes. CONCLUSIONS: This research fills a gap in understanding the public health consequences of SLT and ENDS use by providing objective measures that can signal use of these products alone or in combination with cigarettes.

Smokeless tobacco and periodontitis: A systematic review with meta-analysis.

AIM: The present systematic review with meta-analysis aimed to investigate the global association between smokeless tobacco (SLT) use and periodontitis, considering significant effect size variation based on the income levels of countries. METHODS: We searched seven databases to identify studies that assessed the prevalence of periodontitis in adult SLT users compared to non-users. The quality of studies was evaluated using the 10-item risk-of-bias tool, and publication bias was addressed through the trim-and-fill method. Sensitivity analysis utilized the leave-one-out approach. Meta-analysis and meta-regression, stratified by country income, SLT type, and smoking status, employed robust variance estimation. RESULTS: From an initial pool of 484 studies, 29 studies met the selection criteria and were subjected to qualitative synthesis. Subsequently, data from 19 studies were included in the meta-analysis. SLT users exhibited a nearly threefold greater likelihood of periodontitis compared to non-users (OR = 2.99; 95% CI: 2.10, 4.27; p < .01). The pooled estimate did not vary significantly based on the type of SLT used or concurrent smoking. However, the odds of periodontitis varied according to the economic level of the country; the pooled estimate was higher in high-income countries (OR = 1.69; 95% CI: 1.20, 2.37; p < .01) and even higher in lower-middle-income and lower-income countries (OR = 3.91; 95% CI: 2.66, 5.77; p < .01). CONCLUSIONS: Smokeless tobacco users have a higher likelihood of developing periodontitis. This study underscores global disparities in the SLT-periodontitis relationship, highlighting the need for targeted interventions, particularly in economically challenged areas where SLT use is largely unregulated.

Randomized controlled trial of a text-based smokeless tobacco cessation intervention for rural and medically underserved communities.

INTRODUCTION: Smokeless tobacco use remains prevalent in rural and medically underserved populations, leading to increased rates of tobacco-related cancers and chronic disease. While access to effective cessation programs is limited, text-based interventions may offer a delivery approach with broad reach. This two-armed randomized control trial (RCT) assessed the efficacy of #EnufSnuff.TXT, a text-based smokeless tobacco cessation intervention, in rural and medically underserved communities. METHODS: We conducted a two-arm RCT assessing #EnufSnuff.TXT, a text-based scheduled reduction intervention paired with text-based cessation support messages compared with the modified Enough Snuff intervention comprised of a cessation education booklet and bi-weekly motivational text messages. We recruited participants via social media and surveyed participants at three and six months post-randomization. The primary outcome was self-reported seven-day point prevalence abstinence at six months. RESULTS: We recruited and randomized 532 participants. At three months post randomization, the quit rate was significantly higher in #EnufSnuff.TXT arm compared to the Enough Snuff arm for intent-to-treat (ITT) cases (29.2% vs 19.0%, OR=1.75, p=0.0066). The quit rate at six months post randomization remained higher in #EnufSNuff.TXT compared to Enough Snuff for ITT cases (23.1% vs 20.9%, OR=1.14, p=0.5384), although no longer significantly different. CONCLUSION: This is the first large-scale text-based cessation clinical trial for individuals in underserved areas who use smokeless tobacco. The #EnufSnuff.TXT intervention performed better in the short term, however both interventions yielded similar quit-rates at 6-months post randomization. Future research should focus on improving long-term abstinence in the #EnufSNuff.TXT intervention. IMPLICATIONS: Text-based cessation approaches have the potential to increase access to cessation interventions in rural and medically underserved areas and reduce tobacco-related chronic disease morbidity and mortality. Our study shows short-term efficacy from the first ever randomized controlled trial of a smokeless tobacco cessation intervention, #EnufSnuff.TXT, for rural and medically underserved residents in the United States. Our #EnufSnuff.TXT Intervention offers a scalable solution to reach and provide much needed access to cessation interventions in medically underserved, rural communities in the United States. This work provides the foundation for further inquiry on augmented text-based approaches to increase cessation in this at-risk group.

The effect of nicotine-containing products on peri-implant tissues: A systematic review and network meta-analysis.

INTRODUCTION: Smokers have a higher chance of developing peri-implant diseases and are therefore considered an at-risk population. Our aim was to compare peri-implant characteristics in users of electronic cigarettes (EC), waterpipes (WP), cigarettes (CS), smokeless tobacco (ST), and non-smokers (non-users of any nicotine and tobacco product; NS). METHODS: A systematic search of four electronic databases (PubMed, EMBASE, Web of Science, CENTRAL) was performed until April 2023, restricted to English language. Thirty-nine observational studies were included in the qualitative synthesis, of which 32 studies were included in a Bayesian network meta-analysis. Using a predesigned form, two researchers independently collected data about marginal bone loss (MBL), probing pocket depth (PPD), plaque index (PI), bleeding on probing (BOP), modified plaque index (mPI), probing pocket depth > 4mm (PPD>4), gingival index (GI), peri-implant sulcular fluid (PISF) volume, and TNF-α and IL-1ß levels. QUIPS and CINeMA were used to evaluate the risk of bias and certainty of evidence. RESULTS: NS had the smallest MBL. Most nicotine-containing product users had significantly higher MBL (CS, MD:1.34 CrI: 0.85, 1.79; WP, MD:1.58 CrI: 0.84, 2.35; ST, MD:2.53, CrI: 1.20, 3.87) than NS. EC did not show significant difference compared to NS (MD:0.52 CrI: -0.33, 1.36). In secondary outcomes NS were ranked in first place. Subset analysis based on smoking habit, implant duration, and maintenance control revealed no differences in ranking probability. CONCLUSION: Most nicotine-containing product users presented worse peri-implant parameters compared to non-smokers, while EC users did not show significant differences to NS in many outcomes. IMPLICATION: Alternative nicotine-containing products are gaining popularity and are often considered less harmful by the general public compared to traditional cigarettes. This is the first network meta-analysis comparing users of four nicotine-containing products and non-smokers. This study shows that CS, WP and ST have a detrimental effect on the overall health of peri-implant tissues. EC users also presented inferior parameters compared to NS, however, the difference was not significant in many outcomes. It is essential to educate patients who are using nicotine-containing products, and to provide proper maintenance and appropriate cessation support. Well-designed multi-armed studies are needed for direct comparison of different products, including heated tobacco products. Greater transparency of confounding factors is needed regarding smoking habit and oral hygiene.

Feasibility randomised controlled trial of face-to-face counselling and mobile phone messages compared to usual care for smokeless tobacco cessation in Indian primary care: Project CERTAIN.

INTRODUCTION: Smokeless tobacco (SLT) use in low- and middle-income countries (LMICs) has adverse health consequences. We hypothesize that it is feasible to test an intervention of mobile phone messages and face-to-face counselling session for SLT cessation in India. METHODS: We conducted an exploratory, individual parallel two group, randomised controlled trial (RCT), with baseline -and end-point (three months from randomisation) assessments in urban primary health centres in Odisha, India. A total of 250 current (i.e., users in the last three months) SLT users or dual users (i.e., smokers and SLT users) were recruited to the trial (125 in each group). Participants were randomised to either routine care, face-to-face counselling, and reminder mobile messages or routine care only. The primary outcomes were to assess the feasibility of running a full RCT including recruitment, compliance, and retention. RESULTS: A total seven (77.8%) out of nine primary care centres took part in the trial. Out of the 315 SLT users invited to participate, 250 provided consent and were randomised [79.4% (95% CI: 74.5, 83.7)]. Out of the 250 randomised SLT users, 238 [95% (95% CI: 91.8, 97.5)] were followed up at three months (117 in the intervention group and 121 in the control group). Of the participants in the intervention group, 74 (63.8%) reported that they received the mobile messages. CONCLUSIONS: This exploratory trial demonstrated the feasibility of delivering and evaluating an intervention of mobile phone messages and face-to-face counselling for SLT users in Indian primary care in a full randomised trial. IMPLICATIONS: This study found that combining mobile messages with face-to-face counselling for smokeless tobacco users visiting primary health care settings in India is feasible in terms of recruitment of users, compliance with the intervention, and retention of study participants within the trial.The biochemically verified smokeless tobacco abstinence rate was higher in the intervention group compared with the control groupThere was poor agreement between self-reported tobacco cessation and the measured salivary cotinine in smokeless tobacco users.The findings support the feasibility and acceptability of the intervention signalling the need for a larger clinical trial to test effectiveness of the intervention.

Microbial community and functions involved in smokeless tobacco product: a metagenomic approach.

Smokeless tobacco products (STPs) are attributed to oral cancer and oral pathologies in their users. STP-associated cancer induction is driven by carcinogenic compounds including tobacco-specific nitrosamines (TSNAs). The TSNAs synthesis could enhanced due to the metabolic activity (nitrate metabolism) of the microbial populations residing in STPs, but identifying microbial functions linked to the TSNAs synthesis remains unexplored. Here, we rendered the first report of shotgun metagenomic sequencing to comprehensively determine the genes of all microorganisms residing in the Indian STPs belonging to two commercial (Moist-snuff and Qiwam) and three loose (Mainpuri Kapoori, Dohra, and Gudakhu) STPs, specifically consumed in India. Further, the level of nicotine, TSNAs, mycotoxins, and toxic metals were determined to relate their presence with microbial activity. The microbial population majorly belongs to bacteria with three dominant phyla including Actinobacteria, Proteobacteria, and Firmicutes. Furthermore, the STP-linked microbiome displayed several functional genes associated with nitrogen metabolism and antibiotic resistance. The chemical analysis revealed that the Mainpuri Kapoori product contained a high concentration of ochratoxins-A whereas TSNAs and Zink (Zn) quantities were high in the Moist-snuff, Mainpuri Kapoori, and Gudakhu products. Hence, our observations will help in attributing the functional potential of STP-associated microbiome and in the implementation of cessation strategies against STPs. KEY POINTS: •Smokeless tobacco contains microbes that can assist TSNA synthesis. •Antibiotic resistance genes present in smokeless tobacco-associated bacteria. •Pathogens in STPs can cause infections in smokeless tobacco users.

Prevalence of tobacco use among cancer patients in Iran: a systematic review and meta-analysis.

BACKGROUND: The prevalence of tobacco use among various cancer types in Iran remains a significant concern, necessitating a comprehensive analysis to understand the extent and patterns of consumption. This study aimed to systematically review and analyze existing literature to delineate the prevalence of tobacco use across different cancer types in Iran, thereby providing a robust basis for future interventions and policy formulations. METHODS: Adhering to the PRISMA guidelines, we conducted a systematic review and meta-analysis of literature available in PubMed and Scopus databases. The initial search identified 351 records, out of which 44 studies were selected based on their relevance and design. These studies spanned various time frames, starting from the 2001s up until 2022, and encompassed diverse geographical locations and cancer types in Iran. To avoid bias and potential data overlap, we opted to incorporate a single comprehensive study from the Golestan Cohort, encompassing all data, while excluding 10 other studies. Our final analysis incorporated data from 34 studies, which accounted for 15,425 patients and 5,890 reported smokers. Statistical analyses were performed to calculate the overall proportion of tobacco consumption and to conduct subgroup analyses based on different variables such as cancer types, gender, geographical locations, and types of tobacco used. RESULTS: The analysis revealed a substantial prevalence of tobacco use among cancer patients in Iran, with an overall consumption rate of 43%. This rate varied significantly, ranging from 10 to 88% across individual studies. Subgroup analyses further highlighted disparities in tobacco consumption rates across different demographics, geographic areas, and cancer types. Notably, the 'ever' smokers category exhibited the highest prevalence of tobacco use. The study also identified a worrying trend of high cigarette smoking rates, along with variable consumption patterns of other forms of tobacco, including waterpipe, 'Naas', and 'Pipe'. CONCLUSIONS: This systematic review and meta-analysis underscores a significant association between tobacco consumption and various cancer types in Iran, with a prevalence rate among cancer patients being three times higher than the average Iranian population. The findings indicate substantial heterogeneity in tobacco use patterns, emphasizing the need for targeted interventions to address this pressing health issue. The study serves as a critical resource for shaping future policies and strategies aimed at curbing tobacco use and mitigating its adverse effects on cancer prevalence in Iran.

Process evaluation of a pragmatic feasibility trial on smokeless tobacco cessation intervention delivered in dental hospitals.

BACKGROUND: Article 14 of the WHO 'Framework Convention on Tobacco Control' recommends, that all oral healthcare providers provide support for tobacco cessation, to all patients. Despite evidence on the effectiveness of tobacco cessation interventions in dental settings, implementation remains low in most high-burden countries like Pakistan. A pragmatic pilot trial of a dentist-delivered behavioural support intervention for smokeless tobacco (ST) cessation, was conducted in dental hospitals in Pakistan. This paper presents the findings of the process evaluation of the trial. METHODS: A mixed-method process evaluation of a multi-centre randomised control pilot trial of dentist-delivered behavioural support intervention ST cessation was conducted. The intervention included three sessions namely: pre-quit, quit and post-quit sessions. The process evaluation involved: semi-structured interviews with trial participants (n = 26, of which dental patients were n = 13 and participating dentists were n = 13 conducted from June-August 2022); and fidelity assessment of audio recordings of the intervention sessions (n = 29). The framework approach was used to thematically analyse the interview data. RESULTS: Overall the trial procedures were well accepted, however, young patients expressed uneasiness over revealing their ST use status. The intervention was received positively by dentists and patients. Dentists identified some challenges in delivering behavioural support to their patients. Of these, some were related to the contents of the intervention whereas, others were related to the logistics of delivering the intervention in a clinical setting (such as workload and space). Acceptability of the intervention resources was overall low amongst young patients as they did not take the intervention resources home due to fear of their family members finding out about their ST use. The intervention was successful in achieving the intended impact (in those who engaged with the intervention), i.e., change in the patients' ST use behaviour. Giving up ST with the aid of behavioural support also had an unintended negative effect i.e., the use of harmful substances (cannabis, cigarettes) to give up ST use. Patients' satisfaction with their dental treatment seemed to influence the intervention outcome. CONCLUSION: While there are many variables to consider, but for the participants of this study, behavioural support for abstinence delivered through dentists during routine dental care, appears to be an acceptable and practical approach in helping patients give up ST use, in a country like Pakistan, where negligible support is offered to ST users.

Smokeless tobacco consumption among women of reproductive age: a systematic review and meta-analysis.

Smokeless tobacco (SLT) poses many negative health impacts. Despite its longstanding presence in societies across the world, the health implications of SLT have only been rigorously studied in recent decades. This systematic review and meta-analysis aimed to consolidate existing research to provide a comprehensive understanding of the global prevalence of SLT use among women of reproductive age. Relevant articles were extracted from databases such as PubMed, EMBASE, Web of Science, and Scopus from their inception until November 11, 2023. Observational studies reporting the number of SLT users among women of reproductive age were included. The quality of the studies was assessed using the Joanna Briggs Institute (JBI) tool. The meta-analysis used a random-effects model to determine SLT prevalence, supported by statistical tools like forest plots, I2 statistics, and sensitivity analyses to ensure the accuracy and comprehensiveness of the results. All statistical analyses were performed in R version 4.3. From 10 studies involving 2,053,667 participants, a pooled prevalence for SLT use among women of reproductive age was found to be 9.3% (95% CI: 0.038 to 0.21), with significant heterogeneity among studies (I2 = 100%). Publication bias was suspected among the studies. Sensitivity analysis and subgroup analysis couldn't resolve the heterogeneity. Our analysis shows a significant prevalence of SLT use in women of reproductive age, especially in low socioeconomic and developing countries like India, Pakistan, and Nepal. For women of reproductive age, the use of smokeless tobacco (SLT) can lead to infertility, pregnancy complications, and adverse fetal outcomes, including low birth weight and preterm birth. The results highlight the necessity for specific public health measures and policy changes to decrease SLT consumption among reproductive-age women. Further studies are needed to investigate the reasons behind SLT usage in this group and to assess the impact of intervention strategies, to guide more effective public health initiatives and policies.

Socioeconomic inequality among smoking and smokeless tobacco uses among males in India: a decomposition analysis.

OBJECTIVE: India is the third-largest tobacco manufacturer and its use in India is characterised by a high prevalence of smoking and smokeless (sl) tobacco use. This results in 1 million deaths per year in the country. Given the high burden of tobacco use, this study examines the regional variations and socio-economic correlates of tobacco use in India. METHODS: National Family Health Survey- 5 (2019-2020) have been analysed for the purpose of the study. A sample of 101,839 males aged 15-54 years was included in this study. Primary outcomes of tobacco use were categorised into smoking, smokeless and dual use of smoking and smokeless tobacco use. Bivariate analysis and decomposition analysis was done to study the socio-economic inequality. RESULTS: The prevalence of tobacco use among males in India is around 41 percent. As indicated by the results of the logistics regression, age is positively related to smoking among males. Males aged 45-54 years are 2.5 (95 % concentration index [CI]:2.30-2.63) times probable to smoke, 1.4 (95% CI: 1.30-1.47) times probable of smokeless tobacco consumption and 2.2 (95% CI: 2.10-2.35) times more prone to using both types of substances compared to the younger age group. Males who are widower use smokeless 1.69 times (95% CI: 1.44-1.99) higher with reference to unmarried males. Males belonging to Scheduled tribes are 1.2 (95% CI: 1.13-1.25) times more likely to smoke, 1.3 (95% CI: 1.24-1.37) times more likely to use smokeless substances and 1.4 (95% CI: 1.33-1.47) times more likely to have dual use of tobacco than other social groups. Manual workers (both skilled are unskilled) are likely to smoke (odds ratio [OR] = 1.1, 95% CI: 1.02-1.11), use smokeless tobacco (OR = 1.3, 95% CI: 1.23-1.34) and have dual use of tobacco (OR = 1.29, 95% CI: 1.24-1.34) more than that of other categories. The decomposition of the concentration index shows a significant contribution from factors like a no education, ST/SC caste and wealth index. Among the states and union territories, the prevalence of tobacco is high in West Bengal, Tripura, Mizoram, Manipur, Meghalaya and Sikkim. CONCLUSION: This study is useful for informing target-based prevention policies since it helps in highlighting regions, socio-economic and demographic groups especially vulnerable to tobacco addiction. In India, males from poorer and vulnerable socio-economic backgrounds are more likely to use tobacco. State wise, the eastern zone starting from West Bengal to the North-Eastern states have higher tobacco use than the rest of the country. There is an urgent need to frame policies for controlling the use of tobacco especially among high-risk groups.

A systematic review of cancer risk among users of smokeless tobacco (Swedish snus) exclusively, compared with no use of tobacco.

The main objective of this systematic review was to assess cancer risk, and mortality after cancer diagnosis, for exclusive users of Swedish snus, compared with non-users of tobacco. We followed international standards for systematic reviews and graded our confidence in the risk estimates using the GRADE approach. Our search gave 2450 articles, of which 67 were assessed in full text against our inclusion criteria. Of these, 14 cohort-studies and one case-control study were included in the review. The studies investigated risk of cancer in the oral cavity or oropharynx (3 studies), esophagus (1 study), stomach (1 study), pancreas (2 studies), colorectum (2 studies), anus (1 study) and lung (1 study), as well as malignant lymphoma (1 study), leukemia and multiple myeloma (1 study), melanoma (1 study), any cancer (1 study) and mortality after cancer diagnosis (4 studies). Cancer risk could only be evaluated in men as there was a general lack of data for women. All included studies were evaluated to have a moderate risk of bias, mostly related to validity of exposure information. An increased risk of cancer of the esophagus, pancreas, stomach and rectum as well as an association between use of snus and increased mortality after a cancer diagnosis was reported. Our confidence in the various risk estimates varied from moderate through low to very low.

Exclusive use of different types of tobacco products, exposure to secondhand tobacco smoke and risk of subtypes of head and neck cancer among Indian males.

Tobacco products are used in vary many forms in India. Although the risk of tobacco uses in developing head and neck cancer (HNC) is known, risk by exclusive use of different tobacco products on HNC and its subtypes is poorly understood. A case-control study was conducted at a tertiary cancer hospital, which receives cases from different geographical regions of India with use of different types of tobacco products. The study included 824 oral cavity (OC), 149 oropharynx (OPX) 104 hypopharyngeal (HPX) and 81 larynx (LX) cancer cases and 1206 visitor controls. Information on 11 different types of tobacco products and exposure to secondhand smoke was collected through structured questionnaires. Odds ratios (OR) and 95% confidence intervals (CI), for the association of various HNC subtypes with exclusive use of each tobacco product compared to nonusers of tobacco were estimated using logistic regression models, after adjusting for potential confounders. Exclusive use of any type of smokeless tobacco product was strongly associated with all subtypes of HNC. Gutka chewing (only) had highest risk (OR = 33.67; 95% CI = 19.8-57.0) while exclusive users of betel quid with tobacco (BQ + T), tobacco quid, Khaini, Mawa and Mishri users had a OR of 14.77, 24.20, 5.33, 2.96 and 3.32, respectively, for development of OC. Bidi smoking and secondhand smoke was independently associated with increased risk of HNC. Our study indicates that tobacco control policies should focus on product specific awareness messaging that switching between tobacco product types is not a safe alternative to complete cessation.

The contribution of smoking and smokeless tobacco to oesophageal squamous cell carcinoma risk in the African oesophageal cancer corridor: Results from the ESCCAPE multicentre case-control studies.

Tobacco use is a well-established risk factor for oesophageal squamous cell carcinoma (ESCC) but the extent of its contribution to the disease burden in the African oesophageal cancer corridor has not been comprehensively elucidated, including by type of tobacco use. We investigated the contribution of tobacco use (smoking and smokeless) to ESCC in Tanzania, Malawi and Kenya. Hospital-based ESCC case-control studies were conducted in the three countries. Incident cases and controls were interviewed using a comprehensive questionnaire which included questions on tobacco smoking and smokeless tobacco use. Logistic regression models were used to estimate odds ratios (OR) and their 95% confidence intervals (CI) of ESCC associated with tobacco, adjusted for age, sex, alcohol use, religion, education and area of residence. One thousand two hundred seventy-nine cases and 1345 controls were recruited between August 5, 2013, and May 24, 2020. Ever-tobacco use was associated with increased ESCC risk in all countries: Tanzania (OR 3.09, 95%CI 1.83-5.23), and in Malawi (OR 2.45, 95%CI 1.80-3.33) and lesser in Kenya (OR 1.37, 95%CI 0.94-2.00). Exclusive smokeless tobacco use was positively associated with ESCC risk, in Tanzania, Malawi and Kenya combined (OR 1.92, 95%CI 1.26-2.92). ESCC risk increased with tobacco smoking intensity and duration of smoking. Tobacco use is an important risk factor of ESCC in Tanzania, Malawi and Kenya. Our study provides evidence that smoking and smokeless tobacco cessation are imperative in reducing ESCC risk.

From cultivation to cancer: formation of N-nitrosamines and other carcinogens in smokeless tobacco and their mutagenic implications.

Tobacco use is a major cause of preventable morbidity and mortality globally. Tobacco products, including smokeless tobacco (ST), generally contain tobacco-specific N-nitrosamines (TSNAs), such as N'-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-butanone (NNK), which are potent carcinogens that cause mutations in critical genes in human DNA. This review covers the series of biochemical and chemical transformations, related to TSNAs, leading from tobacco cultivation to cancer initiation. A key aim of this review is to provide a greater understanding of TSNAs: their precursors, the microbial and chemical mechanisms that contribute to their formation in ST, their mutagenicity leading to cancer due to ST use, and potential means of lowering TSNA levels in tobacco products. TSNAs are not present in harvested tobacco but can form due to nitrosating agents reacting with tobacco alkaloids present in tobacco during certain types of curing. TSNAs can also form during or following ST production when certain microorganisms perform nitrate metabolism, with dissimilatory nitrate reductases converting nitrate to nitrite that is then released into tobacco and reacts chemically with tobacco alkaloids. When ST usage occurs, TSNAs are absorbed and metabolized to reactive compounds that form DNA adducts leading to mutations in critical target genes, including the RAS oncogenes and the p53 tumor suppressor gene. DNA repair mechanisms remove most adducts induced by carcinogens, thus preventing many but not all mutations. Lastly, because TSNAs and other agents cause cancer, previously documented strategies for lowering their levels in ST products are discussed, including using tobacco with lower nornicotine levels, pasteurization and other means of eliminating microorganisms, omitting fermentation and fire-curing, refrigerating ST products, and including nitrite scavenging chemicals as ST ingredients.

Status and Determinants of Early Detection of Oral Premalignant and Malignant Lesions in India.

It has been over four decades since the launch of the National Cancer Control Programme in India, yet the cancer screening rates for oral cancer remain unremarkable. Moreover, India is bracing a large burden of oral cancer with poor survival rates. An effective public health programme implementation relies on a multitude of factors related to cost-effective evidence-based interventions, the healthcare delivery system, public health human resource management, community behaviour, partnership with stakeholders, identifying opportunities and political commitment. In this context, we discuss the various challenges in the early detection of oral premalignant and malignant lesions and potential solutions.

Alteration of oral bacteriome of smokeless tobacco users and their association with oral cancer.

Smokeless tobacco (SLT) is certainly one of the major risk factors associated with oral cancer. Disruption of oral microbiota-host homeostasis contributes to the progression of oral cancer. Here, we profiled SLT users' oral bacterial composition and inferred their functions by sequencing 16S rDNA V3-V4 region and PICRUSt2, respectively. Oral bacteriome of SLT users (with or without oral premalignant lesions), SLT with alcohol co-users, and non-SLT consumers were compared. Oral bacteriome is shaped primarily by SLT use and the incidence of oral premalignant lesions (OPL). A significantly increased bacterial α-diversity was monitored in SLT users with OPL compared to in SLT users without OPL and non-users, whereas ß-diversity was significantly explained by OPL status. Overrepresented genera were Prevotella, Fusobacterium, Veillonella, Haemophilus, Capnocytophaga, and Leptotrichia in SLT users having OPL. LEfSe analysis identified 16 genera as a biomarker that were differentially abundant in SLT users having OPL. The functional prediction of genes significantly increased for several metabolic pathways, more importantly, were nitrogen metabolism, nucleotide metabolism, energy metabolism, and biosynthesis/biodegradation of secondary metabolites in SLT users having OPL. Furthermore, HPV-16 and EBV, but not HPV-18, were considerably connected with the SLT users having OPL. Overall, this study provides evidence that SLT utilization and OPL development are associated with oral bacteriome dysbiosis indicating the enrichment of bacterial species known for their contribution to oral carcinogenesis. Therefore, delineating the cancer-inducing bacterial population in SLT users will facilitate the future development of microbiome-targeted therapies. KEY POINTS: • SLT consumption significantly elevates oral bacterial diversity. • Prevalent significant genera are Prevotella, Veillonella, and Haemophilus in SLT users with OPL. • SLT promotes the occurrence of the cancer-inducing bacterial population.

Smokeless tobacco use and public health nutrition: a global systematic review.

OBJECTIVE: Tobacco consumption among low- and middle-income countries where food insecurity remains a challenge poses several concerns. This review examines the available global evidence linking smokeless tobacco (SLT) use with public health nutrition and its implications. DESIGN: Systematic review of articles extracted from PubMed and Scopus from January 2000 to December 2020. SETTING: Included studies that demonstrated the relationship between SLT and nutrition-related factors, that is, BMI, malnutrition, anaemia, poor birth outcomes and metabolic disorders. Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines have been followed to conduct the systematic evidence review. PARTICIPANTS: A total of thirty-four studies were finally used in the systematic review, which included cross-sectional (thirty-one) and cohort (three). RESULTS: SLT use has a huge impact on body weight, alteration in taste, poor oral health, and consumption of fruits and vegetables leading to malnutrition. Maternal use of SLT not only leads to anaemia but also hampers birth outcomes. Increased risk of metabolic syndrome and gallstone disease among SLT users are also well documented in the studies. CONCLUSION: The review highlights the linkages between SLT usage and poor nutritional outcomes. Tobacco control efforts should be convergent with public health nutrition to achieve overall health benefits. Attention is also required to explore suitable mechanisms for SLT cessation combined with enhancing food and nutrition security at the community level in sync with investments in public health nutrition intervention.

Association between snus use and lipid status in Swedish men.

Snus is a common tobacco product in Sweden, but the cardiovascular risk profile for snus users is less known than for cigarette smokers. We examined the association of snus use with lipid status, particularly in comparison to non-tobacco use and cigarette smoking, using data from 5930 men in the Northern Sweden MONICA study. Tobacco use was self-reported in 1986 to 2014 (24.4% used snus) and blood samples were collected at the same time. Harmonized analyses on non-high-density lipoprotein (non-HDL) cholesterol, HDL cholesterol, and triglycerides were conducted in 2016 to 2018. Three hundred eighty-one snus users had also been examined more than once, allowing us to study the effect of discontinued use (achieved by 21.0%). In multivariable linear regression models, snus use was associated with higher HDL cholesterol and triglyceride concentrations compared to non-tobacco use (p values ≤ 0.04), and it was associated with higher HDL cholesterol concentrations and lower triglyceride concentrations compared to cigarette smoking (p values ≤ 0.02). Snus use was not associated with non-HDL cholesterol concentrations, irrespective of the comparison group (p values ≥ 0.07). There was no indication that higher intensity of snus use led to a worse lipid profile, given that high-consumers had higher HDL cholesterol concentrations than low-consumers (p value = 0.02), or that discontinuation of snus use led to a better lipid profile, given that continued users had lower triglyceride concentrations than discontinued users (p value = 0.03). Further studies are needed to confirm or refute our findings.