Oral cancer risk among people who smoke, have quit smoking, use smokeless tobacco, or former smokers that use smokeless tobacco observed from state-based cancer registries

Tobacco use has been identified as a risk factor for oral cancer worldwide. However, relative oral cancer incidence among adults who smoke cigarettes, use smokeless tobacco products (ST), have transitioned from cigarettes to ST, quit cigarettes and/or ST ("quitters"), or never used tobacco has not been well studied. We aim to present population-based oral cancer incidence rates for adults who smoke cigarettes, use ST, are former smokers who now use ST, or quit. We estimated cross-sectional incidence rates and incidence rate ratios (IRRs) using data from statewide cancer registries (Colorado, Florida, North Carolina, and Texas) and population counts derived from national surveys using combined data from 2014-2017. A random-effect meta-analysis approach was used to summarize estimates among these groups, based on multiple imputation-based IRR estimates by state and age group while considering potential heterogeneity. A total of 19,536 oral cancer cases were identified among adult males 35 years and older in the study geographies and period. The oral cancer incidence rate among adults who smoke was significantly higher than the ST group (2.6 times higher, 95% CI 2.0-3.3, P<.001), 3.6 (95% CI 3.2-4.1, P<.001) times higher than the never users, and 2.4 (95% CI 1.8-3.1, P<.001) times higher compared to former smokers who now use ST. The IRR among the ST group relative to never users was 1.4 (95% CI 1.1-1.9, P=.02). The IRR between former smokers who now use ST and those who quit was 1.4 (95% CI 1.0-2.1, P=.08). Findings from this population-based study with a large number of oral cancer cases support significantly high oral cancer incidence among adults who smoke and a lower risk of oral cancer incidence among never users, quitters, users of ST, and former smokers who now use ST compared to cigarettes. Future studies with detailed control of tobacco history and other relevant confounders are needed to confirm these findings.

Background: Oral cancer is the third most common cancer in India which is attributed to the high tobacco burden especially due to a myriad of smokeless tobacco (SLT) products available in the market. Gul/Gul manjan is a commercially-produced, tobacco-based dentifrice, indigenous to rural India and Bangladesh, and mainly used by women. It is both highly addictive and carcinogenic; yet its prevalence, reasons for use and association with oral potentially malignant disorders (OPMDs) and oral cancer are scarcely documented in literature, making this study the first of its kind. Aim: To determine the prevalence of Gul use, its predictors and resultant OPMDs and oral cancer in such consumers. Methods: A cross-sectional study was performed among 3452 individuals visiting the Institute's Oral Health Promotion Clinic between December 2016-March 2018. Their basic demographic details, tobacco use history and abnormalities found on oral examination, were documented in the clinical record form. Data pertaining to Gul users was subjected to further statistical analysis. Results: Of the total individuals screened, 2.9% (n=101, P &lt; 0.001) consumed Gul (89.1% current and 10.9% former users), with majority female consumers (86.1%) from peri-urban Noida. It was used (up to 5 times daily) mainly to alleviate dental pain due to caries/endodontic lesions, which were present in 35.6% users ( P = 0.004). A statistically significant positive association was seen between Gul use and development of OPMDs ( P &lt; 0.001) and oral cancer ( P = 0.001), with 7.9% (n=10; 70% Gul alone users) of the overall leukoplakias/preleukoplakias (n=127), and 7.1% (n=1, Gul alone user) of all the oral cancer cases (n=14), found in Gul users. The duration of Gul use ranged up to 25 years, indicating its high dependency. Conclusion: Gul use is relatively uncommon than other SLT products in India, even among males (the major group of tobacco consumers). Apart from teeth cleaning, Gul is a cheap, easily accessible antidote for acute dental pain relief (owing to nicotine-induced analgesia) among rural women who apply it multiple times daily onto the affected teeth and adjacent gum/mucosa, often leading to its dependency. Courtesy its significant carcinogenic potential which has been clearly reported here (OPMDs and oral cancer development among users), combating/preventing its production, easy availability (in spite of the complete ban on tobacco use in dentifrices) and consumption, is essential. Therefore, the public health challenge of prevention of the use of this form of SLT ie tobacco-based dentifrices, warrants greater interest and action than that has been received thus far, which in turn would contribute to the overall mission of oral cancer prevention.

Tobacco and tobacco-related products have been attributed to be causative factors for oral cancer. Newer, chewable, and commercially available smokeless tobacco (ST) products, such as gutka pose further threat in this direction. The aim of the study was to evaluate the risk of oral cancer associated with gutka and other ST products. A case-control study of 134 cases and 134 controls, over a period of 6 months (July-December 2014), was carried out at the Baqai University, Karachi, Pakistan. An interview-based questionnaire was used to collect data on sociodemographic characteristics, oral hygiene practices and type, duration, and frequency of use of tobacco-related products. Data were analyzed using the Pearson's chi-square (χ2) test with the level of significance set as p < 0.05. Gutka showed the highest odds ratio toward developing oral cancer ratio among all the tobacco-related products [odds ratio (OR) 5.54; 95% CI 2.83-10.83; p < 0.001)]. Participants who consumed other ST products also showed 2 to 4 times higher odds ratio of developing oral cancer than compared to those who did not consume these products. The study provided strong evidence that gutka and other ST products are independent risk factors for oral cancer. This study highlights the strong association of different types of ST and oral cancer. This results in identification of high-risk groups for targeted screening for potential oral cancer lesions.

Medline, Embase, Cancerlit, Toxline were searched, followed by the reference lists of identified reviews and articles. Human cohort or case-control studies in peer-reviewed journals or that were publicly available were selected if they specified study location; examined any form of oral cancer as the outcome; and described use of chewing tobacco, orally used moist snuff or unspecified smokeless tobacco as the exposure. Studies in Asian populations and those with insufficient power where risk estimates and confidence intervals were not reported or could not be calculated were excluded. Standard information was abstracted from each study. Whole-population data were used to estimate numbers of never-smokers. Separate figures for males and females were obtained where possible. Estimates were made of effect size and precision since these were not presented in original studies. Separate meta-analyses were conducted for chewing tobacco, for snuff and for overall smokeless tobacco. Sensitivity analyses for smokers/ nonsmokers were carried out. Heterogeneity was investigated and publication bias assessed using a funnel plot. The 32 studies meeting the inclusion criteria provided 38 heterogeneous study-specific estimates of odds or relative risk ratios (see Tables 1, 2). An increase in risk was mainly evident in studies conducted before 1980. No increase was seen in studies in Scandinavia. The pattern of estimates suggests some publication bias. Smokeless tobacco, as used in America or Europe, carries at most a minor increased risk of oral cancer, but elevated risks in specific populations or from specific products cannot definitely be excluded.

Oral cancers are one of the most prevalent cancers worldwide with almost 300,000 cases reported annually1. In Pakistan, it is the leading type of cancer in men and women after breast cancer. Each year around 16,000 new cases of oral cancers are documented with 5500 cases resulting in death2. There are multiple etiological factors for oral cancers among which the use of smokeless tobacco (SLT) is at the top of the list. SLT is available in different consumable forms such as chewable tobacco, betel leaf, snuff (naswar), Betelnut, etc., which contain a number of carcinogenic substances3. Studies have revealed that naswar is the most common etiological factor of oral cancers among the Pakistani population as compared to the other forms of SLT3. The basic constituents of naswar are slaked lime, powdered tobacco, and indigo which contain more potent carcinogens such as unionized nicotine and tobacco-specific N-nitrosamines, that are specifically harmful to the oral cavity4. It can be used through different routes either inhaled nasally or by placing inside the mouth under the tongue. The nicotine is absorbed into the oral mucosa which is further aided by the increased pH of the mouth by slaked lime5. It has been observed historically that the use of SLT products is very commonly acceptable in Pakistani culture3. The sale and production of naswar are not well regulated and it is being sold by different vendors at cheaper prices and in different package sizes with no such instructions and health warnings written on it1,2. Moreover, some scientific data implicates it as replacement therapy for tobacco smoke cessation as it is a cheaper nicotine substitute1. In 2005, Pakistan formalized the WHO “Framework Convention on Tobacco Control (FCTC),” which addresses the details of the regulation and control of tobacco and SLT products by regulating its price, taxation, packaging, labeling, advertisement, promotion, and sponsorship5. In the last few years, Pakistan has made significant progress in smoking cessation policies but regulation of STL production and taxing is still lagging5,6. A case-control study, conducted in Khyber Pakhtunkhwa, Pakistan, revealed that 68% (men) and 38% (women) of oral cancer patients in Pakistan are due to naswar use. It was also shown that those who used naswar ever in their lifetime have 20 times more risk to develop oral cancers compared with the nonusers of naswar1. Thus, the increasing incidence of oral cancers with the relative use of naswar sets a ground basis for the implementation of strict policies regarding the manufacture and sales of SLT. Studies have provided shreds of evidence that there is a marked decrease in tobacco product use among young people by applying a ban on their promotion and advertisement. Health warnings and relevant constituents written on packages can also be an important tool for minimizing SLT use6. Sticking firmly to the FCTC protocols of smokeless tobacco use is the dire need of time. Furthermore, awareness regarding the harmful effects of STL use should prevail on urban and rural levels as there is a great lack of knowledge among the local population. Ethical approval None. Sources of funding None. Author contribution S.F., O.A.S., G.S., and A.K.: wrote the manuscript. O.A.S. and S.A.: review editing, formatting, and referencing. Conflict of interest disclosure The authors declare that they have no financial conflict of interest with regard to the content of this report. Research registration unique identifying number (UIN) N/A. Guarantor Omer Ahmed Shaikh. Financial Disclosure The author(s) received no financial support for the research, authorship, and/or publication of this article.

Smokeless tobacco products, such as chewing tobacco and snuff, have gained popularity as alternatives to smoking. While the association between smoking and oral health is well-established, the impact of smokeless tobacco on oral health remains a growing concern. It is estimated that the safety risk of smokeless tobacco is similar to that of electronic cigarettes. There is no safe level of smokeless tobacco use. It is correlated with a number of adverse effects such as dental disease, oral cancer, oesophagus cancer, and pancreas cancer, as well as adverse reproductive effects including stillbirth, premature birth, and low birth weight. Smokeless tobacco products contain cancer-causing chemicals. Approximately 28 chemical constituents present in smokeless tobacco. This comprehensive review consolidates existing knowledge on the impact of smokeless tobacco on oral health. It highlights the necessity of targeted interventions, public health campaigns, and further research to address the unique challenges posed by smokeless tobacco. By synthesizing diverse findings, this review contributes to a deeper understanding of the oral health consequences associated with smokeless tobacco use. Key Words: Mucosal changes, Oral health, Periodontal diseases, Smokeless tobacco, Tobacco's impact

India has one of the highest incidences of oral cancer (OC) in the world. OC susceptibility is related to the polymorphism of drug-metabolising genes because they are responsible for metabolising chemical carcinogens, which are present in tobacco and alcohol. The aim of this study was to determine the potential role of drug-metabolising CYP1A1 and GSTM1 gene polymorphisms and the risk of OC in Chhattisgarh. For the assessment of association between the polymorphism of CYP1A1 and GSTM1 genes and risk of tobacco-related OC in Chhattisgarh population, we examined the prevalence of CYP1A1 and GSTM1 null polymorphisms using PCR- and restriction fragment-length polymorphism-based methods in seventy-four histologically confirmed OC patients and in seventy-four age- and sex-matched healthy controls. Demographic information and biological samples were collected by individual-informed written consent of subjects. To know the potential gene–environment interaction, analyses were conducted by stratifying the tobacco (smoking, chewing) and alcohol consumption status and odds ratio (OR) estimation was conducted using SPSS (version 16.0) software. The increased risk for OC was observed among subjects with homozygous CYP1A1 (m2/m2) genotype (OR = 1.39; 95% CI = 0.68–2.84) and GSTM1 null genotype (OR = 1.31; 95% CI = 0.69–2.50). Furthermore, the risk for OC significantly increased in subjects with the homozygous CYP1A1 (m2/m2) genotype with tobacco-chewing and alcohol-drinking history (chewer; OR = 2.08; 95% CI = 0.84–5.20; alcohol drinker; OR = 2.07; 95% CI = 0.69–6.21). The combination of CYP1A1 (m2/m2) and GSTM1 null genotypes is a significant risk for OC (OR = 2.38; 95% CI = 0.678.49, p= 0.031). Our findings indicate that the combined net effect of null mutation on CYP1A1 and GSTM1 genes along with tobacco and alcohol habit increased 2.5-fold risk of OC in Chhattisgarh population.

Oral use of smokeless tobacco has been associated with the development of oral cancer. Shamma is a preparation of smokeless tobacco. Previous investigators in the Kingdom of Saudi Arabia (KSA) have reported a relationship between their patients with oral cancer and a history of using shamma. The purpose of this study was to explore the possible relationship between a smokeless tobacco preparation (shamma) and oral cancer, among the provinces of the KSA. Tumor Registry (TR) data from the King Faisal Specialist Hospital and Research Centre (KFSH&RC) were reviewed for the period from 1976 to 1995. A total of 26510 Saudi cancer patients were referred over this 20-year period. The frequency of oral cancer was investigated, specifically for those primary sites located near the habitual placement of this smokeless tobacco product. Notably, 35.4% of these oral cancers were referred from one province - Jizan. The percentage of oral cancer cases from this province is significantly higher than the percentage of total malignant cases referred to KFSH&RC from this province, and the Saudi population of this province when compared to the whole of the KSA. These data suggest that there is a relationship between the factors smokeless tobacco product (shamma), frequency of oral cancer, and Jizan province: oral cancer appears to be more common in this province where shamma is also common.

The U.S. Food and Drug Administration (FDA) is required by law to inform the public about levels of harmful and potentially harmful tobacco constituents in a format that is "understandable and not misleading to a lay person." Our study addresses a critical gap in research on communicating such information for smokeless tobacco (SLT) products. The design included random assignment to one of the experimental (online interactive) conditions differing in presentation format or a control condition (receiving no information). Experimental respondents viewed information on levels and health risks of 5 harmful constituents in up to 79 products. Outcome measures included knowledge of health risks of constituents, perception of constituent variability in SLT products, disease risk ratings, self-reported SLT use, and side-by-side product comparisons. The sample of 333 SLT users, 535 cigarette smokers, and 663 nontobacco users participated at baseline, time of intervention, and 6 weeks postintervention. Presentation formats showed few systematic differences so were combined in analyses. Experimental condition respondents increased their knowledge about constituent health effects and their perceptions of constituent variability in SLT products, from baseline to postintervention, and relative to the control condition. Changes in respondents' ratings of disease risk and their estimates of constituent exposure from specific products were observed, but not in self-reported SLT use. Interactive online graphic and numeric presentation formats can be efficient in increasing people's knowledge of health effects and perceived variation of constituents in SLT products. Further research on longer-term behavioral assessment, and usefulness of this approach for regulatory agencies, is needed. Research on communicating the information about harmful constituents in SLT products to lay persons is critically lacking. This study proposes novel formats for effective communication about the levels and the health effects of SLT constituents to multiple user groups. The lack of misperceptions among study participants that some tobacco products are safe suggests that such formats can potentially be used for public display of SLT constituent data by the FDA and regulatory agencies in other countries.

Smokeless tobacco use is a significant part of the overall world tobacco problem. When the habit is introduced early in life, it increases the chance for permanent addiction and primes adolescents for use of harder drugs, exposing them to higher risk of oral cancer and other adverse effects of tobacco. This baseline study aimed at providing descriptive information on smokeless tobacco knowledge and use among adolescents at a time just before the ban on such products was enforced nationally on 1st December 2006. Six out of 101 primary and four out of 11 secondary schools were randomly selected in Ilala Municipality, Tanzania. A total of 1011 students were randomly selected and interviewed; boys (mean age = 14.5 years) accounted for 50.7% and girls (mean age = 13.6 years) 49.3%. The prevalence of tobacco use was 5.9% (boys = 9%; girls = 2.4%). Prevalence of smokeless tobacco use was 3.6%, about half of all who have ever smoked. Most popular brand of smokeless tobacco reported was Kuberi (44.8%) followed by Gutka (6.9%). Twelve (41%) of the smokeless tobacco users were using the products almost everyday. Among the reasons reported for smokeless tobacco use were pleasure (27.6%), smell (17.2%) and taste (6.9%). However, 48.3% of the users did not know why they used the product for the first time. Smokeless tobacco products were branded as nutritional supplements with different tastes and strengths, ideal for enticing the curiosity of adolescents. Given the crafty practice of the tobacco industry and salesmen, there is need for monitoring of availability of these products in circulation and enforcement of the ban nationally and globally to institute measures for effective elimination of this harmful practice.

BackgroundNaswar, a smokeless tobacco product, commonly consumed in Pakistan, is associated with a 10-fold increase in the risk of oral cancer. However, little is known about Naswar’s underlying toxicity mechanisms.ObjectiveThe current study aimed to investigate the effects of Naswar use on oral health and salivary parameters.MethodsA case-control study was conducted among Naswar users (n=42) and age-matched healthy controls (n=42) in Pakistan in 2019. Participant data were collected using questionnaires. Decayed, missing, and filled teeth (DMFT) scores were computed during clinical examinations. Unstimulated whole saliva was collected to assess salivary flow rate, pH, and salivary total oxidative stress (TOS)/total antioxidant capacity (TAC) using commercially available kits. Participants' oral health parameters were compared between cases and controls using ANOVA.ResultsNo significant differences were observed between the two groups in terms of age, oral health, and hygiene practices and mean DMFT score. Mean salivary pH and the salivary flow rate was significantly (p<0.001) higher in Naswar users (7.7 and 0.71 mL/minute, respectively) than in non-users (6.95 and 0.52 mL/minute, respectively). Although TOS and TAC were not significantly different between the groups, Naswar users generally had a higher TOS (51.6±42 µmol/L) and lower TAC (0.55±0.18 mmol/L) than non-users (TOS 45.5±38.2 µmol/L and TAC 0.57±0.17 mmol/L). Correlational analysis also revealed a significant positive correlation between DMFT score and Naswar use duration (r=0.796, p<0.001) and the number of dips/units consumed each day (r=0.515; p<0.001).ConclusionHabitual Naswar use is associated with increased salivary flow rate, pH, and TOS, and reduced TAC levels in Pakistani adults compared to non-users. The pro-oxidant changes may contribute toward deleterious effects of Naswar use including oral cancer.

Smokeless tobacco (ST) is a tobacco product that is used by means other than smoking. Evidence was available that ST products is a known risk factor for oral precancerous and cancers for long, with greater risk for oral cancer than others. The prospective, descriptive study has carried out to evaluate the relationship between the use of smokeless tobacco and oral cancer.Biopsy samples have collected from 60 patients, whose have attended to Al-Gamhouria Teaching Hospital and histo-pathological private labs in Aden using a questionnaire during the period of 12 months. The sections from paraffin-embedded tissue specimens were stained with hematoxylin and eosin (H &amp; E). A section containing the full thickness of the tumors have used for histopathological grading.The prevalence of oral squamous cell carcinoma (OSCC) lesions showed different grade of differentiation among 60 studied patients cases, the Well differentiation squamous cell carcinoma (WDSCC) was the highest percentage (70%). No significant difference noticed in well-differentiated SCCs (WDSCC) between men (36.7%) and women (33.3 %; P &lt; 0.05). The moderate differentiation SCC (MDSCC), and the poor differentiation SCC (PDSCC) represented (20% &amp; 10%) respectively. According to the age of patients, WDSCC, MDSCC and PDSCC highest percentage age group was (51-60) years. Male were predominant in both genders, male to female ratio 1.2: 1. Anatomical sites of all OSCC lesions had analyzed and revealed that tongue was the most prevalent site (33.3%), followed by the buccal mucosa, (23.3%) , floor of mouth (16.7%) , lip (13.3%), Gingiva (8.3%), and the least prevalent site was the hard palate represented (5%) of all cases., the chief etiological factor which we observed, was tobacco, in the form of smoking tobacco used by 75% of the patients followed by smokeless tobacco product users, in form of shamma chewers, (61.7%), and in form of Hot sachet (58.3%), and Zarda users represented 51.7% of cases.Our results indicate that the occurrence of OSCC among studied cases showed different grade of differentiation, age and gender have some relation with the presence of OSCC. and it is high association with risk habits of tobacco use in different forms particularly smokeless tobacco.

Menthol has long been incorporated as a flavor additive in tobacco products and can impact use behaviors. Despite its inclusion in some of the most popular flavored smokeless tobacco (ST) products (eg, "mint" flavored products), few studies have systematically investigated the impact of menthol on ST use behaviors in prospective empirical studies. Rigorous investigation of ST menthol content on behavioral and physiological outcomes requires ST products with stable and precise levels of menthol; however, commercial product composition variability prevents product comparisons when evaluating the effects of systematic changes in menthol content on clinical outcomes. We developed amended loose moist snuff ST products by treating commercially available, unflavored loose ST with an ethanol-based menthol spiking solution or a nonmentholated ethanol control solution to develop test products with different levels of menthol: 0, 1, 3, and 5 mg menthol/g tobacco. We evaluated the stability of menthol content in these products over 24 months and evaluated menthol exposure associated with the products through pharmacokinetic analysis of plasma menthol-glucuronide in human participants (n = 22). Menthol content of the amended products was on target, homogenous, and stable for up to 24 months. Menthol exposure (menthol-glucuronide Cmax and AUC) significantly differed between each test product. These data suggest that stable products with nonoverlapping menthol content can be developed using a menthol spiking solution and can be subsequently administered for clinical assessments of mentholated loose ST. The results from this study suggest that a menthol spiking solution can be used to mentholate unflavored, loose ST to a target menthol content. With this method, the ST menthol content was stable for at least 24 months, and the products exposed users to menthol in a dose-dependent manner. This method yielded loose ST products with precise, stable levels of menthol to allow systematic evaluation of ST menthol content on clinical outcomes. The method may have applications for systematically evaluating changes in other tobacco product ingredients.

Addictive, toxic, and carcinogenic constituents present in smokeless tobacco (SLT) products are responsible for the harmful effects associated with SLT use. There are limited data on levels of such constituents in SLT products used in Africa, a region with high prevalence of SLT use and the associated morbidity and mortality. Manufactured and custom-made SLT products were purchased from five African countries (South Africa, Uganda, Mauritania, Nigeria, and Zambia) using a standard approach for sample collection, labeling, and storage. Moisture content, pH, total and unprotonated (biologically available) nicotine, five tobacco-specific N-nitrosamines (TSNA), 10 polycyclic aromatic hydrocarbons (PAH), five metals and metalloids (As, Cd, Cr, Ni, and Pb), nitrate, and nitrite were analyzed. A total of 54 samples representing 15 varieties of manufactured SLT products and 13 varieties of custom-made SLT products were purchased and analyzed. In all samples, the total nicotine ranged from 1.6 to 20.5 mg/g product and unprotonated nicotine accounted for 5.3-99.6% of the total nicotine content. The sum of all five TSNA ranged from 1.6 to 100 μg/g product, with significant within-country variations observed across both the manufactured and custom-made varieties. Significant variations were also found for PAH, metals and metalloids, nitrates, and nitrites. This is the most comprehensive report on the chemical profiling of products from African countries. This is also the first study illustrating the variability of harmful constituents within the same types and brands of African SLT. Our findings emphasize the need for consumer education and interventions to reduce SLT use in Africa. The data reported here can be useful to regulators in considering measures to prevent the occurrence of high levels of known toxicants and carcinogens in manufactured products.

Assessing dental students’ knowledge of oral cancer in The United Arab Emirates