BACKGROUND: This study delves into the intricate landscape of oral cancer, a global concern with a high incidence in Asian countries. We focus on oral squamous cell carcinoma (OSCC), primarily driven by the consumption of betel nut and its derivatives. OSCC often arises from premalignant lesions like oral submucous fibrosis (OSF). In Pakistan, OSCC is prevalent among men due to various addictive substances, including smokeless tobacco and chewing materials. Mutations in tumor suppressor genes, such as TP53 and p21, play crucial roles in this malignancy\'s development. We also explore the involvement of TUSC3 gene deletion in OSCC and OSF.
METHODS: In this study we investigated demographics, TUSC3 gene expression, deletion analysis, and TP53 and p21 genetic alterations in OSCC and OSF patients (blood and tissue of 50 samples in each condition) who had tobacco derivates usage history. The association analysis was carried out mainly through PCR based genotyping.
RESULTS: The study\'s patient cohort (OSCC and OSF) displayed a wide age range from 13 to 65 years (Mean = 32.96 years). Both conditions were more prevalent in males, with a male-female ratio of approximately 2.5:1. Chewing habits analysis revealed high frequencies of gutka use in both OSF and OSCC patients. TUSC3 expression analysis in OSCC cell lines indicated significant downregulation. Genotyping showed no TUSC3 deletion in OSF cases, but a deletion rate of over 22% in OSCC tissue samples. Analysis supported a significant association of TUSC3 deletion with OSCC development but not with OSF. Polymorphism in p53 exon 4 and p21 (rs1801270) were significantly associated with both OSCC and OSF, adding to their pathogenesis. Our findings further revealed a strong correlation between TUSC3 deletion and the excessive use of tobacco and related products, shedding light on the genetic underpinnings of OSCC development.
CONCLUSIONS: Notably, our study provides a crucial insight into genetic aspects underlying OSCC and OSF in response of addictive consumption of areca nut, betel quid, and tobacco derivatives. A significant association between TUSC3 deletion and OSCC development, along with polymorphisms in TP53 and p21, underscores the importance of further research into the molecular mechanisms driving oral cancer progression for improved diagnosis and treatment outcomes.

Oropharyngeal cancers (OPCs) in Asia account for 42% of the global burden and over 50% of related deaths. Human papillomavirus (HPV) is involved in over 70% of OPC cases in the Western hemisphere, but its role in the Eastern hemisphere is unclear. This study reviews OPC epidemiology, including prevalence, etiological factors (such as smokeless tobacco and HPV), and their interaction. Among the SEAR countries, India had the highest incidence of HPV-related OPCs at 38.4%, while data were unavailable for most African countries, with only a 14% incidence reported. Conversely, the American region exhibited one of the highest HPV positivity rates, reaching up to 65% in different states of the USA, while Brazil reported an incidence of up to 38%. In the European Union, the UK had the highest incidence of HPV-associated OPC, reaching up to 52%. In the Western Pacific region, New Zealand demonstrated the highest incidence at up to 78%. Smokeless tobacco consumption was higher in SEAR countries, which had a relatively lower incidence of HPV infection, suggesting a negative correlation between the two. Based on our literature search, the most common detection methods used globally are immunohistochemistry for p16 and polymerized chain reaction. OPCs are a global health concern, and proper identification and classification are vital. HPV-driven cancers have better survival rates, emphasizing the need for focused research on specific problem areas based on the burden of HPV-positive or HPV-negative cancers.

BACKGROUND: Expanding knowledge on tobacco use and quitting outcomes in Chhattisgarh, India, is crucial. Limited data hinder the assessment of tobacco use prevalence and quitting outcomes in the region. This household-based cross-sectional study aimed to assess smokeless tobacco (SLT) use and quit behaviour among village dwellers aged 35-44 and 65-74 years in Jamul, Chhattisgarh.
METHODS: A survey was conducted among 450 participants, utilising a pretested questionnaire and data analysis using IBM Statistical Package for the Social Sciences (SPSS) v23.
RESULTS: The study revealed that among the survey participants, 61.1% were males and 38.9% were females. The prevalence of SLT use was found to be 67.8%, with 59.1% of current SLT users reporting daily use. Middle-aged individuals predominantly chose gutkha, while khaini was more common among the elderly. Tobacco and paan with tobacco were also commonly used forms. Gudakhu, a popular SLT product for oral hygiene and easy defecation, was reported by 71.34% of participants. Television warnings and SLT packages proved to be successful methods for disseminating information about the dangers of SLT use. However, SLT users who attempted to quit independently reported encountering one or more withdrawal symptoms, which posed significant obstacles to quitting SLT.
CONCLUSIONS: Community-based awareness programmes are implemented via regional television (TV) channels, coupled with cessation initiatives, including professional counselling, pharmaceutical interventions and support of peer. Changing attitudes against SLT use and promoting tobacco-free environments are prioritized. These strategies will effectively address SLT use and improve quitting outcomes in Jamul, Chhattisgarh, fostering a healthier community.

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.

BACKGROUND: Tobacco use is widely recognised as a significant risk factor for oral cancer and periodontal diseases. However, the relationship between various types of tobacco use and dental caries has been inconsistent. This study aimed to determine the association between smoking and smokeless tobacco and dental caries among patients in a tertiary care hospital in Quetta, Pakistan.
METHODS: This cross-sectional study was conducted from November 2020 to March 2021 among patients in a tertiary care hospital in Quetta, Pakistan. Oral examinations and interviews were performed according to the WHO Oral Health Survey basic methods (5th edition) to determine dental caries status, tobacco use, and oral health behaviours. The odds ratio and binary logistic regression were analysed to assess the association between the types (smoking tobacco, smokeless tobacco, and use of both types), duration, and frequency of tobacco use and high caries level (DMFT ≥ 5).
RESULTS: Four hundred participants aged 18-65 were included, and 67.8% were tobacco users. Use of both smoking and smokeless tobacco (aOR = 14.7, 95%CI = 1.87-115.96, p = 0.011), smokeless tobacco only (aOR = 5.90, 95%CI = 1.89-18.37, p = 0.002), and smoking only (aOR = 2.18, 95%CI = 1.23-3.88, p = 0.008) were associated with significantly increased risk of high caries. Using tobacco for longer periods and more frequently daily also significantly increases the risk of high caries.
CONCLUSIONS: Smoking and smokeless tobacco are significantly associated with high dental caries after adjusting for other factors. Due to the high severity of dental caries and the high prevalence of tobacco use among Pakistani patients in this study, it is highly recommended to strengthen policies aimed at reducing tobacco usage, including smokeless forms.

OBJECTIVE: Smokeless tobacco (ST) use in South Asia is high, yet interventions to support its cessation are lacking. We tested the feasibility of delivering interventions for ST cessation in South Asia.
METHODS: We used a 2 × 2 factorial design, pilot randomized controlled trial with a duration of 26 weeks, including baseline and follow-up (6, 12 and 26 weeks) assessments.
METHODS: Two primary health-care facilities each in Dhaka (Bangladesh) and Karachi (Pakistan) and a walk-in cancer screening clinic in Noida (India) took part.
METHODS: Adult daily ST users willing to make a quit attempt within 30 days. Of 392 screened, 264 participants [mean age: 35 years, standard deviation = 12.5, 140 (53%) male] were recruited between December 2020 and December 2021; 132 from Bangladesh, 44 from India and 88 from Pakistan.
METHODS: Participants were randomized to one of three treatment options [8-week support through nicotine replacement therapy (NRT, n = 66), a behavioural intervention for smokeless tobacco cessation in adults (BISCA, n = 66) or their combination (n = 66)] or the control condition of very brief advice (VBA) to quit (n = 66).
METHODS: Recruitment and retention, data completeness and feasibility of intervention delivery were evaluated. Biochemically verified abstinence from tobacco, using salivary cotinine, was measured at 26 weeks.
RESULTS: Retention rates were 94.7% at 6 weeks, dropping to 89.4% at 26 weeks. Attendance in BISCA pre-quit (100%) and quit sessions (86.3%) was high, but lower in post-quit sessions (65.9%), with variability among countries. Adherence to NRT also varied (45.5% Bangladesh, 90% India). Data completion for key variables exceeded 93% among time-points, except at 26 weeks for questions on nicotine dependence (90%), urges (89%) and saliva samples (62.7%). Among follow-up time-points, self-reported abstinence was generally higher among participants receiving BISCA and/or NRT. At 26 weeks, biochemically verified abstinence was observed among 16 (12.1%) participants receiving BISCA and 13 (9.8%) participants receiving NRT.
CONCLUSIONS: This multi-country pilot randomized controlled trial of tobacco cessation among adult smokeless tobacco users in South Asia demonstrated the ability to recruit and retain participants and report abstinence, suggesting that a future definitive smokeless tobacco cessation trial is viable.

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.

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.
CONCLUSIONS: 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.

Tobacco use significantly influences the oral microbiome. However, less is known about how different tobacco products specifically impact the oral microbiome over time. To address this knowledge gap, we characterized the oral microbiome of cigarette users, smokeless tobacco users, and non-users over 4 months (four time points). Buccal swab and saliva samples (n = 611) were collected from 85 participants. DNA was extracted from all samples and sequencing was carried out on an Illumina MiSeq, targeting the V3-V4 region of the 16S rRNA gene. Cigarette and smokeless tobacco users had more diverse oral bacterial communities, including a higher relative abundance of Firmicutes and a lower relative abundance of Proteobacteria, when compared to non-users. Non-users had a higher relative abundance of Actinomyces, Granulicatella, Haemophilus, Neisseria, Oribacterium, Prevotella, Pseudomonas, Rothia, and Veillonella in buccal swab samples, compared to tobacco users. While the most abundant bacterial genera were relatively constant over time, some species demonstrated significant shifts in relative abundance between the first and last time points. In addition, some opportunistic pathogens were detected among tobacco users including Neisseria subflava, Bulleidia moorei and Porphyromonas endodontalis. Overall, our results provide a more holistic understanding of the structure of oral bacterial communities in tobacco users compared to non-users.

OBJECTIVE: India has the highest number of smokeless tobacco (SLT) products available in different forms, consumed in various ways. The current study aimed to understand the pattern of daily SLT use according to different product categories and whether Quit intention and Quit attempts vary by SLT type and exposure to media messages.
METHODS: Data from Global Adult Tobacco Surveys (GATS), 2016-17, was used to find access to media messages and warning labels by SLT type. Quit attempt and Quit intention were calculated for each of the SLT types. Logistic regression analyses were employed to identify whether access to media messages, warning labels influenced, quit intention and attempts vary by SLT type.
RESULTS: Khaini or tobacco lime mixture was the most common SLT type consumed by 37% of SLT users, whereas SLT users consuming more than one product accounted for 23% of SLT users. Exposure to media messages and warning labels was high among Gutkha/ paan masala tobacco users (74.7% and 81.2%) and low among oral tobacco (Mishri, Gul, Gudakhu) users (56.1% and 60.0%). Quit attempts and quit intention were high among Gutkha/ paan masala tobacco users (38.3% and 22.3%) and low among oral tobacco (Mishri, Gul, Gudakhu) users (25.3% and 13.6%). Users of Oral tobacco and khaini or tobacco-lime mixture were significantly less likely to attempt quitting (AOR 0.806(95%CI: 0.676-0.962), 0.839(95%CI: 0.736-0.956), and have quit intention (AOR 0.681(95%CI: 0.702-0.976), 0.733(95%CI: 0.627-0.857) compared to Gutkha/ paan masala with tobacco users.
CONCLUSIONS: The reach of media messages and warning labels varies by SLT type. Quit intention and attempts vary by SLT type and access to media messages and warning labels. There is a need to re-strategise the tobacco control Information, Education and Communication (IEC) to reach out with effective messaging to the most unreached.