Cytomorphological Changes of Oral Mucosal Cells Among Smokeless Tobacco Users in Low and Middle-Income Country Settings: Insights from Pakistan

Cytomorphological Changes of Oral Mucosal Cells Among Smokeless Tobacco Users in Low and Middle-Income Country Settings: Insights from Pakistan | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Cytomorphological Changes of Oral Mucosal Cells Among Smokeless Tobacco Users in Low and Middle-Income Country Settings: Insights from Pakistan Sabreen Hassan, Ayesha Sifat, Muhammad Munib, Saliha Saeed, Waqar U Nisa, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4878492/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 23 Dec, 2024 Read the published version in BMC Oral Health → Version 1 posted 10 You are reading this latest preprint version Abstract Background: Chronic tobacco use, in any form, induces significant cellular alterations in the oral mucosa. This study investigates four distinct cytomorphological changes in oral mucosal cells among smokeless tobacco users, examining their association across different genders and age groups. Materials and methods: This cross-sectional study involved collecting mucosal samples from smokeless tobacco (naswar) users through consecutive sampling. The prepared smears were examined for dysplastic changes. Data analysis was performed using SPSS, with Chi-square tests and logistic regression employed to evaluate proportions and associations. Results: Among 100 Naswar users, the labial sulcus mucosa was the most common site affected (47%). The most frequent cytomorphological change was micronuclei (46%), followed by nuclear budding (25%), perinuclear halo (18%), and binucleated cells (14%). In the 51-60 age group, micronuclei (78.9%), nuclear budding (55.3%), binucleation (31.6%), and perinuclear halo (36.8%) were more prevalent (P < 0.005). Gender analysis revealed that micronuclei were more common in females (54.2%) compared to males (43.4%), while nuclear budding was more prevalent in males (27.6%) than females (P < 0.28). Logistic regression indicated that individuals aged 51-60 were more likely to exhibit micronuclei (OR = 1.15, 95% CI: 0.22 to 5.83, P = 0.863) and nuclear budding (OR = 5.34, 95% CI: 9.23 to 30.75, P < 0.05). Conclusion: The dysplastic changes observed included micronuclei, nuclear budding, binucleated cells, and perinuclear halo, with micronuclei being the most prevalent. These findings could facilitate the early diagnosis of oral lesions and their timely management in habitual smokeless tobacco users. Oral lesions smokeless tobacco naswar cellular alterations micronuclei oral cancer Introduction Oral cancer, predominantly squamous cell carcinoma (SCC), represents one of the most significant health challenges worldwide. The etiology of oral cancer (OC) is complex, with genetic, environmental, social, and behavioral factors playing crucial roles. Among these, tobacco and alcohol consumption are the primary risk factors, contributing significantly to the disease's development. Environmental factors such as alcohol, ultraviolet radiation, and tobacco products damage DNA, increase p53 expression and activate gene clusters associated with cell growth and death. All regions of the oral cavity, including the tongue, roof of the mouth, gums, and cheeks, are susceptible to cancer from tobacco use( 1 , 2 ). According to WHO fact sheets, tobacco consumption by the global population was 22.3%, with 36.7% male population followed by female population 7.8%( 3 ). According to estimates, approximately 25.4 million Pakistani adult population consumed tobacco products in 2022, placing Pakistan at 7th position globally in tobacco product users( 4 ). In the Khyber Pakhtunkhwa, Naswar is a prevalent form of smokeless tobacco (60%) used by the majority of the population( 5 ). Naswar contains over three hundred carcinogenic agents, including nicotine and nitrosamines, which can induce dysplasia and contribute to carcinogenesis. The carcinogenic potential of tobacco is influenced by the quantity, frequency, and duration of use. Early histological changes from tobacco use range from hyper-parakeratosis to epithelial dysplasia. It often takes 20 to 50 years of continuous smokeless tobacco use to initiate malignant changes in the oral mucosa ( 6 , 7 ). Despite advancements in surgical techniques, radiation, and chemotherapy, the five-year survival rate for oral cancer remains stagnant at about 50–55%. Early-stage oral cancer can masquerade as harmless lesions, making early detection critical for improving morbidity and mortality rates( 8 ). Several diagnostic methods exist for early oral cancer detection, including clinical examination and cytological studies of oral cells. Oral exfoliative cytology, a simple and non-invasive technique, is well-accepted by patients and effective for early diagnosis of oral cancer, including epithelial atypia and SCC. Early detection could prevent 80% of deaths, as 60% of oral cancers are advanced by the time of diagnosis. In the early stages, oral cancer appears as an innocent lesion, often leading to delayed reporting and more invasive treatments. Exfoliative cytology offers a straightforward, non-invasive diagnostic tool for early detection of premalignant and malignant oral lesions, potentially improving survival and morbidity rates. Timely diagnosis and cessation of Naswar use could revert the affected mucosa to a normal state( 9 , 10 ). This study aims to determine the cytomorphological changes in oral mucosal cells among smokeless tobacco users and examine the association with gender and age groups. Materials and Methods Study Design and Setting: A cross-sectional study was conducted at Sardar Begum Dental Hospital, Peshawar, Khyber Pakhtunkhwa, Pakistan, from November 2020 to January 2023, following approval from the Ethical Committee of the University of Gandhara. Participants: The study utilized a non-probability consecutive sampling technique. The sample consisted of 100 regular smokeless tobacco users (at least 5 years of Naswar use), with equal representation from both genders. Participants were aged 20–60 years. Exclusion criteria included cigarette smokers, alcoholics, users of other smokeless tobacco types (e.g., bidi, gutka, paan), individuals with systemic diseases (e.g., blood disorders, renal failure, diabetes mellitus), and those who had received radiotherapy and/or chemotherapy. Informed consent was obtained from all participants for both the procedure and the use of their data for research purposes. Data Collection: Participants were instructed to rinse their mouths with water. Cytological smears were collected using a brush and wooden spatula from the area where naswar was placed. The smear was transferred to a dry glass slide immediately. The slides were fixed in 95% ethanol and stained with Papanicolaou (PAP) and May-Grunwald Giemsa (MGG) stains, each requiring different fixation methods. PAP stain required immediate fixation in 95% alcohol, while MGG stain required air-drying before fixation in methanol. The stained smears were then observed under 40X and 100X magnifications to identify dysplastic changes such as micronuclei, multinucleation or binucleation, nuclear budding, and perinuclear halo. Statistical Analysis: Data were analyzed using SPSS Version 20. Continuous variables (age, duration) were presented as mean ± standard deviation (SD) while these were later on transformed to categorical variables. Categorical variables (gender, site, amount of Naswar used, duration of Naswar use, clinical presentation, and cytomorphological changes) were analyzed using the Chi-square test to determine the distribution of cytomorphological parameters among different independent variables. Multi-logistic regression was applied to check for associations and confounders to get an adjusted odds ratio (AOR) considering variables with significant p-values. A p-value ≤ 0.05 was considered statistically significant. Results The study included 100 participants with a mean age of 45.89 ± 10.14 years, categorized into different age groups. Most participants were male (76%). The labial sulcus mucosa was the most common site for mucosal changes (47%), followed by the buccal sulcus mucosa (41%), with only 12% involving the floor of the mouth. Notably, 94% of participants used less than one pack of smokeless tobacco daily. The most frequent duration of smokeless tobacco use was 10–20 years (48%). Clinically, 65% of users had a reddened or yellowish-white wrinkled appearance of the mucosa. The most common cytomorphological changes observed were micronuclei (46%), followed by nuclear budding (25%), perinuclear halo (18%), and binucleated nuclei (14%) ( Table 1 ). Table 1 Demographic and Usage Characteristics of Smokeless Tobacco Users Variables Categories Frequency Percentage Age 20–30 years 11 11 31–40 years 23 23 41–50 years 29 29 51–60 years 37 37 Gender Male 76 76 Female 24 24 Site of smokeless tobacco placement Labial sulcus 47 47 Buccal sulcus 43 43 Floor of the mouth 10 10 Amount of smokeless tobacco 1 pack 6 6 Duration of smokeless tobacco 10–20 years 48 48 21–30 years 30 30 31–40 years 22 22 Clinical presentation Normal colouration with slight wrinkled mucosa 25 25 Reddened or yellowish white wrinkled mucosa 65 65 Heavily wrinkled, thickened, deep reddened furrows 10 10 Cytomorphological changes Micronuclei 46 46 Nuclear budding 25 25 Perinuclear halo 18 18 Bi nucleation 14 14 Descriptive statistic of continuous variable like age and duration of naswar Mean Std. Deviation Range Minimum Maximum Age 45.89 10.147 40 20 60 Duration 21.16 7.091 25 10 35 Micronuclei were predominantly present in the 51–60 years age group (78.9%, P < 0.001), with no presence in the 20–30 years group. Similarly, nuclear budding was most common in the 51–60 years age group (55.3%, P < 0.001), with no presence in the 20–30 and 31–40 years groups. Gender-wise, micronuclei were more frequently reported in females (54.2%) compared to males (43.4%), with a P value of 0.35. In contrast, nuclear budding was more common in males (27.6%) than females, with a P value of 0.28 ( Table 2 ). Table 2 Distribution of Micronuclei and Nuclear Budding among Smokeless Tobacco Users by Age, Gender, Site, Amount, Clinical Presentation, and Duration Variable Cytomorphological Changes Micro Nuclei P value* Nuclear budding P value* Level Present Not Present Level Present Not Present Age 20–30 0(0.0%) 10(100.0%) <.001 20–30 0(0.0%) 10(100.0%) < .001 31–40 4(18.2%) 18(81.8%) 31–40 0(0.0%) 22(100.0%) 41–50 12(40.0%) 18(60.0%) 41–50 49(13.3%) 26(86.7%) 51–60 30(78.9%) 8(21.1%) 51–60 21(55.3%) 17(44.7%) Gender Male 33(43.4%) 43(56.6%) 0.35 Male 21(27.6%) 55(72.4%) 0.28 Female 13(54.2%) 11(45.8%) Female 4(16.7%) 20(83.3%) Site Labial 22(46.8%) 25(53.2%) 0.005 Labial 11(23.4%) 36(76.6%) 1 pack daily 44(46.8%) 50(53.2%) 0.68 > 1 pack daily 24(25.5%) 70(74.5%) 1.0 < 1 pack daily 2(33.3%) 4(66.7%) < 1 pack daily 1(16.7%) 5(83.3%) Clinical Picture Normal 0(0.0%) 25(100.0%) < .001 Normal 0(0.0%) 25(100.0%) <.001 Wrinkled 36(55.4%) 29(44.6%) Wrinkled 16(24.6%) 49(75.4%) Heavily wrinkled 10(100.0%) 0(0.0%) Heavily wrinkled 9(90.0%) 1(10.0%) Duration 20–30 1(2.1%) 47(97.9%) < .001 10_20 0(0.0%) 25(100.0%) < .001 21–30 23(76.7%) 7(23.3%) 21–30 16(24.6%) 49(75.4%) 31–40 22(100.0%) 0(0.0%) 31–40 9(90.0%) 1(10.0%) P vlue ≤ .05 was taken as significant. * Chi Square test The floor of the mouth was significantly more affected by both micronuclei (90%, P = 0.005) and nuclear budding (80%, P < 0.001). The labial sulcus mucosa showed a 46.8% presence of micronuclei (P = 0.005) and a 23.4% presence of nuclear budding (P < 0.001). There was no significant difference in micronuclei presence between users of more than one pack daily (46.8%) and those using less than one pack daily (33.3%) (P = 0.68). Similarly, there was no significant difference in nuclear budding related to the amount of daily usage (P = 1.0). Participants with wrinkled mucosa had a higher presence of micronuclei (55.4%, P < 0.001) and nuclear budding (24.6%, P < 0.001). Heavily wrinkled mucosa showed 100% presence of micronuclei and 90% presence of nuclear budding. Regarding the duration of use, micronuclei were significantly more present in participants with 31–40 years of smokeless tobacco use (100%, P < 0.001). Nuclear budding was most common in the 21–30 years group (76.7%, P < 0.001) ( Table 3 ). Table 3 Distribution of Binucleated Cells and Perinuclear Halo among Smokeless Tobacco Users by Age, Gender, Site, Amount, Clinical Presentation, and Duration Variable Cytomorphological Changes Bi Nucleated P value* Peri Nuclear Halo P value* Level Present Not Present Level Yes No Age 20–30 0(0.0%) 10(100%) 0.001 20–30 0(0.0%) 10(100.0%) 0.002 31–40 0(0.0%) 22(100%) 31–40 1(4.5%) 21(95.5%) 41–50 2(6.7%) 28(93.3%) 41–50 3(10.0%) 27(90.0%) 51–60 12(31.6%) 26(68.4%) 51–60 14(36.8%) 24(63.2%) Gender Male 11(14.5%) 65(85.5%) 1 Male 14(18.4%) 62(81.6%) 1 Female 3(12.5%) 21(87.5%) Female 4(16.7%) 20(83.3%) Site Labial 6(12.8%) 41(87.2%) 0.005 Labial 7(14.9%) 40(85.1%) 0.004 Buccal 3(7.0%) 40(93.0%) Buccal 5(11.6%) 38(88.4%) Mouth floor 5(50.0%) 5(50.0%) Mouth Floor 6(60.0%) 4(40.0%) Amount > 1 pack daily 13(13.8%) 81(86.2%) 1 > 1 pack daily 17(18.1%) 77(81.9%) 1 < 1 pack daily 1(16.7%) 5(83.3%) < 1 pack daily 1(16.7%) 5(83.3%) Clinical Picture Normal 0(0.0%) 25(100.0%) < .001 Normal 0(0.0%) 25(100.0%) < .001 Wrinkled 5(7.7%) 60(92.3%) Wrinkled 10(15.4%) 55(84.6%) Heavily wrinkled 9(90.0%) 1(10.0%) Heavily wrinkled 8(80.0%) 2(20.0%)1112(20.0%) Duration 10_20 0(0.0%) 48(100.0%) < .001 10_20 0(0.0%) 48(100.0%) < .001 21–30 0(0.0%) 30(100.0%) 21–30 7(7(23.3%) 23(76.7%) 31–40 14(63.6%) 8(36.4%) 31–40 11(50.0%) 11(50.0%) P value ≤ .05 was taken as significant. * Chi Square test was applied. Logistic regression analysis in Table 4 revealed that participants in the 51–60 years age group were more likely to exhibit micronuclei (OR = 1.15, 95% CI: 0.22 to 5.83, P = 0.863). Similarly, participants in the 51–60 years age group were 5.34 times more likely to show nuclear budding (OR = 5.34, 95% CI: 9.23 to 30.75, P < 0.05). Table 4 Multi Logistic Regression Analysis of Cytomorphological Changes in Smokeless Tobacco Users Dependent variable Independent variable P value AOR* 95% Confidence interval Lower Upper Micro Nuclei Presence (Yes/No) Ref Age(20–30) 31–40 0.13 0.29 0.058 1.44 41–50 0.075 0.239 0.05 1.15 51–60 0.863 1.153 0.228 5.83 Site Ref(Labial) Buccal 0.555 0.76 0.301 1.90 Mouth floor 0.016 04.5 04.82 42.02 Nuclear budding Presence (Yes/No) Ref Age(20–30) 31–40 0.482 1.902 0.316 11.44 41–50 0.464 1.925 0.333 11.11 51–60 0.05 5.34 9.23 30.75 Site Ref(Labial) Buccal 0.566 1.314 0.517 3.337 Mouth floor 0.075 4.70 0.853 25.844 Bi Nucleated Presence (Yes/No) Ref Age(20–30) 31–40 0.923 0.883 0.07 11.08 41–50 0.876 0.825 0.073 9.31 51–60 0.314 3.189 0.333 30.52 Site Ref(Labial) Buccal 0.663 0.755 0.213 2.671 Mouth floor 0.152 3.002 0.666 13.522 *Adjusted Odds Ratio Discussion The objective of this study was to determine the cytological changes in oral mucosal cells among smokeless tobacco (naswar) users, examining markers such as micronuclei, nuclear budding (broken-egg nuclei), binucleated cells, and perinuclear halo (indicative of HPV virus), and their distribution across gender and age groups. Our findings showed that 46% of cases exhibited micronuclei, 25% had nuclear buds, 14% had binucleated cells, and 18% had a perinuclear halo. Few studies have explored these aspects. Smokeless tobacco consumption not only increases the chances of dental caries( 11 ) and deterioration of periodontal health( 12 ) but also causes cell abnormalities, for instance, binucleation and cellular atypia( 13 , 14 ). Another study reported that the micronuclei count in smokeless tobacco users was higher than in non-smokers/non-users( 15 ). These findings align with other studies that showed an increased frequency of micronuclei in smokeless tobacco users compared to control groups. Typical cellular changes among tobacco users, including nuclear enlargement indicative of HPV presence, were observed in some buccal smears. Similarly, a local study reported a significant cellular and nuclear diameter increase among naswar users( 16 ). A study described "broken egg nuclei" and binucleated cells, noting that these cells result from chromosome aberrations and failure to complete mitosis( 17 ). Our observations of cytomorphological changes match previous studies, suggesting a common biological pathway in humans. Of the 100 participants, 76% of smokeless tobacco users were male, and 24% were female. Most users were in their 5th and 6th decades (51–60 years), with a mean age of 38 years (SD ± 2.34). These findings are consistent with a study conducted in Nangarhar, which found that 80% of males and 20% of females used naswar( 18 ). A study revealed that about 15% of males and 10% of females aged 25–64 years regularly used chewing tobacco or snuff( 19 ). This demographic trend may be due to similar social and cultural factors, highlighting that our society is male-dominated, with easy access to naswar. Our results indicate that the most common site for naswar placement was the labial mucosa (47%), followed by the buccal mucosa (41%), with the floor of the mouth being the least common site. This contrasts with a study conducted in the same geographical location that presented the buccal mucosa as the most common site for smokeless tobacco placement( 12 ). Other studies also predominantly reported buccal mucosa involvement. However, in our study, local smokeless tobacco users believed the labial sulcus played a significant role in sedation, making it the most common site. Ninety-four percent of participants used less than one pack daily, with 48% having used smokeless tobacco for 10–20 years. These results align with a study of 40 snuff users, where 31 participants used less than one box per day, seven used one box per day, and two used more than one box per day( 16 ). Our study's setting was private sector, where high socioeconomic individuals seek treatment and have higher education levels, which may explain the lower frequency of naswar use among highly educated individuals. Oral mucosal changes due to snuff usage are well-documented( 20 – 22 ). It is known that snuff causes damage to the oral cavity, resulting in thick, wrinkled, and discolored mucosa at the site of placement( 14 , 23 ). In our study, 25% of smokeless tobacco users had normal coloration with slight wrinkling, 65% had reddened or yellowish-white wrinkled mucosa, and 10% had heavily wrinkled, thickened mucosa with deep, reddened furrows. It is assumed that longer naswar use leads to more apparent mucosal changes. Strengths and Weaknesses: This study presents several strengths, including its innovative focus on the cytological changes induced by smokeless tobacco (naswar) on oral mucosal cells. Utilizing exfoliative cytology, a non-invasive technique, allows for early detection of potential malignancies, which is patient-friendly and practical for clinical settings. The study's specific focus on a population in Khyber Pakhtunkhwa, Pakistan, provides localized insights into regional practices and their health impacts, contributing valuable information for targeted public health interventions. However, several weaknesses should be noted. Firstly, the study did not conduct a formal sample size calculation, which could affect the statistical power and generalizability of the findings. The use of non-probability sampling and recruitment from a private dental hospital limits the generalizability to the broader population. Additionally, the cross-sectional design precludes longitudinal assessment of the long-term effects of naswar use on the oral mucosa. Furthermore, while necessary, the exclusion criteria may not fully account for all potential confounding factors, such as variations in diet and oral hygiene practices, which could influence the study outcomes. Lastly, the study's scope was limited to cytological changes without investigating potential molecular or genetic alterations associated with naswar use. Conclusion Smokeless tobacco use, specifically habitual naswar chewing, can cause significant changes in the oral mucosa, detectable through exfoliative cytology. The cytological changes observed in this study included micronuclei, nuclear budding (broken eggs), binucleation, and perinuclear halo. These changes were prevalent among men, particularly in their 5th and 6th decades of life. The labial mucosa was the most common site for naswar placement, followed by the buccal mucosa, with varied clinical presentations. To better understand these effects and confirm these findings, further studies with larger sample sizes, standardized parameters, and advanced techniques are needed. Declarations Ethical Approval & Consent for Participation: Ethical approval was given by the Ethical Committee, Gandhara University, Peshawar – Pakistan. The participants also gave written informed consent for participation in the study and data sharing. All the procedures were performed according to the relevant guidelines and regulations – Declaration of Helsinki. Consent for Publication: Not applicable Availability of data: All the data generated and analyzed in this study is included in this article. Competing Interest: No financial or non-financial competing interests. Funding: The authors did not receive any funding to conduct this study. Authors’ Contribution: Study Design – S. H. D, F. A. K, S. A, Data Collection – S. H, W. U. N, Analysis –F. A. K Z. U. H, Data Interpretation – All authors, Draft the work – All authors, Revision – S. H, F. A. K, S. A, A. R. Acknowledgments: NA Clinical Trial Number: Not applicable Authors Information: Sabreen Hassan 1 , Ayesha Sifat 2 , Mohammad Munib 3 , Saliha Saeed 4 , Waqar U Nisa 5 Sofia Haider Durrani 6 , Abid Rahim 6 , Naeem Ullah 7 , Saima Afaq 2,8* , Farhad Ali Khattak 1* , Zia Ul Haq 2 Khyber College of Dentistry, Peshawar – Pakistan Khyber Medical University, Peshawar - Pakistan Swat Medical College, Swat – Pakistan Dental College, HITEC – IMS, Taxila – Pakistan Bacha Khan Dental College, Mardan – Pakistan Gandhara University, Peshawar - Pakistan Saidu Medical College, Swat - Pakistan Department of Health Sciences, University of York, York – UK Institute of Public Health and Social Sciences, Khyber Medical University, Peshawar - Pakistan * Corresponding authors: Fahad Ali Khattak (Assistant Professor Biostatistics, Khyber College of Dentistry, Peshawar, Pakistan. https://orcid.org/0000-0002-5933-270X; Email: [email protected] ) Saima Afaq (Department of Health Sciences, University of York, York – UK Email: [email protected] , [email protected] ) References Tan Y, Wang Z, Xu M, Li B, Huang Z, Qin S et al. 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Cite Share Download PDF Status: Published Journal Publication published 23 Dec, 2024 Read the published version in BMC Oral Health → Version 1 posted Editorial decision: Revision requested 21 Oct, 2024 Reviews received at journal 18 Oct, 2024 Reviews received at journal 09 Oct, 2024 Reviewers agreed at journal 09 Oct, 2024 Reviewers agreed at journal 18 Sep, 2024 Reviewers invited by journal 07 Sep, 2024 Editor invited by journal 04 Sep, 2024 Editor assigned by journal 28 Aug, 2024 Submission checks completed at journal 28 Aug, 2024 First submitted to journal 08 Aug, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4878492","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":357279039,"identity":"e8d72c57-02a9-4a70-8250-b9c10aae7fa5","order_by":0,"name":"Sabreen Hassan","email":"","orcid":"","institution":"Khyber College of Dentistry, Peshawar","correspondingAuthor":false,"prefix":"","firstName":"Sabreen","middleName":"","lastName":"Hassan","suffix":""},{"id":357279040,"identity":"fdd21f03-c479-493f-9f50-66e332464333","order_by":1,"name":"Ayesha Sifat","email":"","orcid":"","institution":"Khyber Medical University","correspondingAuthor":false,"prefix":"","firstName":"Ayesha","middleName":"","lastName":"Sifat","suffix":""},{"id":357279041,"identity":"bf10250d-1fa8-4a6d-9341-3ac47de60d89","order_by":2,"name":"Muhammad Munib","email":"","orcid":"","institution":"Swat Medical College, Swat","correspondingAuthor":false,"prefix":"","firstName":"Muhammad","middleName":"","lastName":"Munib","suffix":""},{"id":357279043,"identity":"51cd4a22-717a-4428-a538-6351508533a3","order_by":3,"name":"Saliha Saeed","email":"","orcid":"","institution":"Dental College, HITEC – IMS, Taxila","correspondingAuthor":false,"prefix":"","firstName":"Saliha","middleName":"","lastName":"Saeed","suffix":""},{"id":357279045,"identity":"ed40906f-2bc4-4cfd-81d4-ff4c2064c1e6","order_by":4,"name":"Waqar U Nisa","email":"","orcid":"","institution":"Bacha Khan Dental College, Mardan","correspondingAuthor":false,"prefix":"","firstName":"Waqar","middleName":"U","lastName":"Nisa","suffix":""},{"id":357279047,"identity":"7b58d740-9eae-406d-8c7a-80a3fb82513f","order_by":5,"name":"Sofia Haider Durrani","email":"","orcid":"","institution":"Gandhara University,Peshawar","correspondingAuthor":false,"prefix":"","firstName":"Sofia","middleName":"Haider","lastName":"Durrani","suffix":""},{"id":357279049,"identity":"77c03bec-a4ac-463c-803d-1bb36c5cfffe","order_by":6,"name":"Abid Rahim","email":"","orcid":"","institution":"Gandhara University,Peshawar","correspondingAuthor":false,"prefix":"","firstName":"Abid","middleName":"","lastName":"Rahim","suffix":""},{"id":357279050,"identity":"0e0c3cd4-e773-4b83-b297-3525601cd762","order_by":7,"name":"Naeem Ullah","email":"","orcid":"","institution":"Saidu Medical College, Swat","correspondingAuthor":false,"prefix":"","firstName":"Naeem","middleName":"","lastName":"Ullah","suffix":""},{"id":357279051,"identity":"c859de6f-9710-46fa-bf7b-840f80618bd9","order_by":8,"name":"Saima Afaq","email":"","orcid":"","institution":"Department of Health Sciences, University of York","correspondingAuthor":false,"prefix":"","firstName":"Saima","middleName":"","lastName":"Afaq","suffix":""},{"id":357279052,"identity":"18dc3791-1dd7-4373-b737-cd001f078c6e","order_by":9,"name":"Farhad Ali Khattak","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA3ElEQVRIiWNgGAWjYBAC9gYGNgYGtgQGhuMNQK6BBWEtPAdgWs4cAGmRIEXLjQQQnxgt7GefPfhRlibPd/P51Q0/CiQY+Nu7E/Br4Uk3N+w5l2M483ZO2c0eoMMkzpzdgFeLPUMamwRvW0WCwe2ctBs8QC0GErn4tfDwP2OT/AvScvNM2s0/RGmRSGOT5m3LSTC4wX7sNnG2SDxjk5Y5l2Y480wO220ZAwkegn7h4U9jk3xTlizPd/z4s5tv/tjI8bf34teCrNsATBKrHATYH5CiehSMglEwCkYQAAD/2kX/WGShIgAAAABJRU5ErkJggg==","orcid":"","institution":"Khyber College of Dentistry, Peshawar","correspondingAuthor":true,"prefix":"","firstName":"Farhad","middleName":"Ali","lastName":"Khattak","suffix":""},{"id":357279053,"identity":"8843cc1a-bb56-4db9-bc41-5262dc3c3a51","order_by":10,"name":"Zia Ul Haq","email":"","orcid":"","institution":"Khyber Medical University","correspondingAuthor":false,"prefix":"","firstName":"Zia","middleName":"Ul","lastName":"Haq","suffix":""}],"badges":[],"createdAt":"2024-08-08 06:15:16","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4878492/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4878492/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12903-024-05220-7","type":"published","date":"2024-12-23T15:57:06+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":72640488,"identity":"161768fe-4b7d-4ae5-af12-29e4a10a522a","added_by":"auto","created_at":"2024-12-30 16:05:56","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":725543,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4878492/v1/db8d7273-eaa9-42de-8203-2aaf69a148d3.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Cytomorphological Changes of Oral Mucosal Cells Among Smokeless Tobacco Users in Low and Middle-Income Country Settings: Insights from Pakistan","fulltext":[{"header":"Introduction","content":"\u003cp\u003e Oral cancer, predominantly squamous cell carcinoma (SCC), represents one of the most significant health challenges worldwide. The etiology of oral cancer (OC) is complex, with genetic, environmental, social, and behavioral factors playing crucial roles. Among these, tobacco and alcohol consumption are the primary risk factors, contributing significantly to the disease's development. Environmental factors such as alcohol, ultraviolet radiation, and tobacco products damage DNA, increase p53 expression and activate gene clusters associated with cell growth and death. All regions of the oral cavity, including the tongue, roof of the mouth, gums, and cheeks, are susceptible to cancer from tobacco use(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAccording to WHO fact sheets, tobacco consumption by the global population was 22.3%, with 36.7% male population followed by female population 7.8%(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). According to estimates, approximately 25.4\u0026nbsp;million Pakistani adult population consumed tobacco products in 2022, placing Pakistan at 7th position globally in tobacco product users(\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). In the Khyber Pakhtunkhwa, Naswar is a prevalent form of smokeless tobacco (60%) used by the majority of the population(\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). Naswar contains over three hundred carcinogenic agents, including nicotine and nitrosamines, which can induce dysplasia and contribute to carcinogenesis. The carcinogenic potential of tobacco is influenced by the quantity, frequency, and duration of use. Early histological changes from tobacco use range from hyper-parakeratosis to epithelial dysplasia. It often takes 20 to 50 years of continuous smokeless tobacco use to initiate malignant changes in the oral mucosa (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). Despite advancements in surgical techniques, radiation, and chemotherapy, the five-year survival rate for oral cancer remains stagnant at about 50\u0026ndash;55%. Early-stage oral cancer can masquerade as harmless lesions, making early detection critical for improving morbidity and mortality rates(\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eSeveral diagnostic methods exist for early oral cancer detection, including clinical examination and cytological studies of oral cells. Oral exfoliative cytology, a simple and non-invasive technique, is well-accepted by patients and effective for early diagnosis of oral cancer, including epithelial atypia and SCC. Early detection could prevent 80% of deaths, as 60% of oral cancers are advanced by the time of diagnosis. In the early stages, oral cancer appears as an innocent lesion, often leading to delayed reporting and more invasive treatments. Exfoliative cytology offers a straightforward, non-invasive diagnostic tool for early detection of premalignant and malignant oral lesions, potentially improving survival and morbidity rates. Timely diagnosis and cessation of Naswar use could revert the affected mucosa to a normal state(\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThis study aims to determine the cytomorphological changes in oral mucosal cells among smokeless tobacco users and examine the association with gender and age groups.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy Design and Setting:\u003c/h2\u003e \u003cp\u003e A cross-sectional study was conducted at Sardar Begum Dental Hospital, Peshawar, Khyber Pakhtunkhwa, Pakistan, from November 2020 to January 2023, following approval from the Ethical Committee of the University of Gandhara.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eParticipants:\u003c/h2\u003e \u003cp\u003eThe study utilized a non-probability consecutive sampling technique. The sample consisted of 100 regular smokeless tobacco users (at least 5 years of Naswar use), with equal representation from both genders. Participants were aged 20\u0026ndash;60 years. Exclusion criteria included cigarette smokers, alcoholics, users of other smokeless tobacco types (e.g., bidi, gutka, paan), individuals with systemic diseases (e.g., blood disorders, renal failure, diabetes mellitus), and those who had received radiotherapy and/or chemotherapy. Informed consent was obtained from all participants for both the procedure and the use of their data for research purposes.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eData Collection:\u003c/h2\u003e \u003cp\u003e Participants were instructed to rinse their mouths with water. Cytological smears were collected using a brush and wooden spatula from the area where naswar was placed. The smear was transferred to a dry glass slide immediately. The slides were fixed in 95% ethanol and stained with Papanicolaou (PAP) and May-Grunwald Giemsa (MGG) stains, each requiring different fixation methods. PAP stain required immediate fixation in 95% alcohol, while MGG stain required air-drying before fixation in methanol. The stained smears were then observed under 40X and 100X magnifications to identify dysplastic changes such as micronuclei, multinucleation or binucleation, nuclear budding, and perinuclear halo.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis:\u003c/h2\u003e \u003cp\u003eData were analyzed using SPSS Version 20. Continuous variables (age, duration) were presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (SD) while these were later on transformed to categorical variables. Categorical variables (gender, site, amount of Naswar used, duration of Naswar use, clinical presentation, and cytomorphological changes) were analyzed using the Chi-square test to determine the distribution of cytomorphological parameters among different independent variables. Multi-logistic regression was applied to check for associations and confounders to get an adjusted odds ratio (AOR) considering variables with significant p-values. A p-value\u0026thinsp;\u0026le;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eThe study included 100 participants with a mean age of 45.89\u0026thinsp;\u0026plusmn;\u0026thinsp;10.14 years, categorized into different age groups. Most participants were male (76%). The labial sulcus mucosa was the most common site for mucosal changes (47%), followed by the buccal sulcus mucosa (41%), with only 12% involving the floor of the mouth. Notably, 94% of participants used less than one pack of smokeless tobacco daily. The most frequent duration of smokeless tobacco use was 10\u0026ndash;20 years (48%). Clinically, 65% of users had a reddened or yellowish-white wrinkled appearance of the mucosa. The most common cytomorphological changes observed were micronuclei (46%), followed by nuclear budding (25%), perinuclear halo (18%), and binucleated nuclei (14%) \u003cb\u003e(\u003c/b\u003eTable\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e\u003cb\u003e).\u003c/b\u003e\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDemographic and Usage Characteristics of Smokeless Tobacco Users\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003eCategories\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003eFrequency\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003ePercentage\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003e20\u0026ndash;30 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003e31\u0026ndash;40 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e23\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003e41\u0026ndash;50 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e29\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003e51\u0026ndash;60 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e37\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eGender\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e76\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e76\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e24\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eSite of smokeless tobacco placement\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003eLabial sulcus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e47\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003eBuccal sulcus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e43\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003eFloor of the mouth\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eAmount of smokeless tobacco\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;1 pack\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e94\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e94\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;1 pack\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eDuration of smokeless tobacco\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003e10\u0026ndash;20 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e48\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e48\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003e21\u0026ndash;30 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003e31\u0026ndash;40 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e22\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eClinical presentation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003eNormal colouration with slight wrinkled mucosa\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003eReddened or yellowish white wrinkled mucosa\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e65\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003eHeavily wrinkled, thickened, deep reddened furrows\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003eCytomorphological changes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003eMicronuclei\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e46\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003eNuclear budding\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003ePerinuclear halo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003eBi nucleation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eDescriptive statistic of continuous variable like age and duration of naswar\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMean\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eStd. Deviation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eRange\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003eMinimum\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eMaximum\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e45.89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10.147\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e60\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eDuration\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21.16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7.091\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e35\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eMicronuclei were predominantly present in the 51\u0026ndash;60 years age group (78.9%, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001), with no presence in the 20\u0026ndash;30 years group. Similarly, nuclear budding was most common in the 51\u0026ndash;60 years age group (55.3%, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001), with no presence in the 20\u0026ndash;30 and 31\u0026ndash;40 years groups. Gender-wise, micronuclei were more frequently reported in females (54.2%) compared to males (43.4%), with a P value of 0.35. In contrast, nuclear budding was more common in males (27.6%) than females, with a P value of 0.28 \u003cb\u003e(\u003c/b\u003eTable\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e\u003cb\u003e).\u003c/b\u003e\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003e Distribution of Micronuclei and Nuclear Budding among Smokeless Tobacco Users by Age, Gender, Site, Amount, Clinical Presentation, and Duration\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"9\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003ctbody\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"8\" nameend=\"c9\" namest=\"c2\"\u003e \u003cp\u003eCytomorphological Changes\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003eMicro Nuclei\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eP value*\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e \u003cp\u003eNuclear budding\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eP value*\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLevel\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePresent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNot Present\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eLevel\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003ePresent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNot Present\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20\u0026ndash;30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0(0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10(100.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003e\u0026lt;.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e20\u0026ndash;30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0(0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e10(100.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e31\u0026ndash;40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4(18.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e18(81.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e31\u0026ndash;40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0(0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e22(100.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e41\u0026ndash;50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12(40.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e18(60.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e41\u0026ndash;50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e49(13.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e26(86.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e51\u0026ndash;60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30(78.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8(21.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e51\u0026ndash;60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e21(55.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e17(44.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eGender\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e33(43.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e43(56.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e21(27.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e55(72.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.28\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13(54.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11(45.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e4(16.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e20(83.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eSite\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLabial\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22(46.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e25(53.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e0.005\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eLabial\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e11(23.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e36(76.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBuccal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15(34.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e28(65.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eBuccal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e6(14.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e37(86.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMouth floor\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9(90.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1(10.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMouth floor\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e8(80.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2(20.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eAmount\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;1 pack daily\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e44(46.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e50(53.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;1 pack daily\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e24(25.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e70(74.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e1.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;1 pack daily\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2(33.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4(66.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;1 pack daily\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1(16.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e5(83.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eClinical Picture\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNormal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0(0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e25(100.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNormal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0(0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e25(100.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e\u0026lt;.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eWrinkled\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e36(55.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e29(44.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eWrinkled\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e16(24.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e49(75.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHeavily wrinkled\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10(100.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0(0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eHeavily wrinkled\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e9(90.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1(10.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eDuration\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20\u0026ndash;30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1(2.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e47(97.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e10_20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0(0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e25(100.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21\u0026ndash;30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23(76.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7(23.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e21\u0026ndash;30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e16(24.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e49(75.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e31\u0026ndash;40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22(100.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0(0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e31\u0026ndash;40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e9(90.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1(10.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"9\" nameend=\"c9\" namest=\"c1\"\u003e \u003cp\u003eP vlue\u0026thinsp;\u0026le;\u0026thinsp;.05 was taken as significant.\u003c/p\u003e \u003cp\u003e\u003cb\u003e*\u003c/b\u003eChi Square test\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe floor of the mouth was significantly more affected by both micronuclei (90%, P\u0026thinsp;=\u0026thinsp;0.005) and nuclear budding (80%, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The labial sulcus mucosa showed a 46.8% presence of micronuclei (P\u0026thinsp;=\u0026thinsp;0.005) and a 23.4% presence of nuclear budding (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). There was no significant difference in micronuclei presence between users of more than one pack daily (46.8%) and those using less than one pack daily (33.3%) (P\u0026thinsp;=\u0026thinsp;0.68). Similarly, there was no significant difference in nuclear budding related to the amount of daily usage (P\u0026thinsp;=\u0026thinsp;1.0).\u003c/p\u003e \u003cp\u003eParticipants with wrinkled mucosa had a higher presence of micronuclei (55.4%, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and nuclear budding (24.6%, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Heavily wrinkled mucosa showed 100% presence of micronuclei and 90% presence of nuclear budding. Regarding the duration of use, micronuclei were significantly more present in participants with 31\u0026ndash;40 years of smokeless tobacco use (100%, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Nuclear budding was most common in the 21\u0026ndash;30 years group (76.7%, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) \u003cb\u003e(\u003c/b\u003eTable\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e\u003cb\u003e).\u003c/b\u003e\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDistribution of Binucleated Cells and Perinuclear Halo among Smokeless Tobacco Users by Age, Gender, Site, Amount, Clinical Presentation, and Duration\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"9\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003ctbody\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"8\" nameend=\"c9\" namest=\"c2\"\u003e \u003cp\u003eCytomorphological Changes\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003eBi Nucleated\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eP value*\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e \u003cp\u003ePeri Nuclear Halo\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eP value*\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLevel\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePresent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNot Present\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eLevel\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20\u0026ndash;30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0(0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10(100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e20\u0026ndash;30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0(0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e10(100.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e31\u0026ndash;40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0(0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e22(100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e31\u0026ndash;40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1(4.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e21(95.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e41\u0026ndash;50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2(6.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e28(93.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e41\u0026ndash;50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e3(10.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e27(90.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e51\u0026ndash;60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12(31.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e26(68.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e51\u0026ndash;60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e14(36.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e24(63.2%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eGender\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11(14.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e65(85.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e14(18.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e62(81.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3(12.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e21(87.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e4(16.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e20(83.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eSite\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLabial\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6(12.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e41(87.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e0.005\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eLabial\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e7(14.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e40(85.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e0.004\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBuccal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3(7.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e40(93.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eBuccal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e5(11.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e38(88.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMouth floor\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5(50.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5(50.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMouth Floor\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e6(60.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e4(40.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eAmount\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;1 pack daily\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13(13.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e81(86.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;1 pack daily\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e17(18.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e77(81.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;1 pack daily\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1(16.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5(83.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;1 pack daily\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1(16.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e5(83.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eClinical Picture\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNormal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0(0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e25(100.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNormal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0(0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e25(100.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eWrinkled\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5(7.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e60(92.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eWrinkled\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e10(15.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e55(84.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHeavily wrinkled\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9(90.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1(10.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eHeavily wrinkled\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e8(80.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2(20.0%)1112(20.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eDuration\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10_20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0(0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e48(100.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e10_20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0(0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e48(100.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21\u0026ndash;30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0(0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e30(100.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e21\u0026ndash;30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e7(7(23.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e23(76.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e31\u0026ndash;40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14(63.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8(36.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e31\u0026ndash;40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e11(50.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e11(50.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"9\" nameend=\"c9\" namest=\"c1\"\u003e \u003cp\u003eP value\u0026thinsp;\u0026le;\u0026thinsp;.05 was taken as significant.\u003c/p\u003e \u003cp\u003e\u003cb\u003e*\u003c/b\u003eChi Square test was applied.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eLogistic regression analysis in Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e revealed that participants in the 51\u0026ndash;60 years age group were more likely to exhibit micronuclei (OR\u0026thinsp;=\u0026thinsp;1.15, 95% CI: 0.22 to 5.83, P\u0026thinsp;=\u0026thinsp;0.863). Similarly, participants in the 51\u0026ndash;60 years age group were 5.34 times more likely to show nuclear budding (OR\u0026thinsp;=\u0026thinsp;5.34, 95% CI: 9.23 to 30.75, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eMulti Logistic Regression Analysis of Cytomorphological Changes in Smokeless Tobacco Users\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eDependent variable\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eIndependent variable\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eAOR*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e95% Confidence interval\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLower\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eUpper\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"6\" rowspan=\"7\"\u003e \u003cp\u003e\u003cb\u003eMicro Nuclei\u003c/b\u003e Presence\u003c/p\u003e \u003cp\u003e(Yes/No)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRef Age(20\u0026ndash;30)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c6\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e31\u0026ndash;40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.058\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.44\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e41\u0026ndash;50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.075\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.239\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.15\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e51\u0026ndash;60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.863\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.153\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.228\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e5.83\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSite Ref(Labial)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBuccal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.555\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.76\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.301\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.90\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMouth floor\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.016\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e04.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e04.82\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e42.02\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"6\" rowspan=\"7\"\u003e \u003cp\u003e\u003cb\u003eNuclear budding\u003c/b\u003e\u003c/p\u003e \u003cp\u003ePresence\u003c/p\u003e \u003cp\u003e(Yes/No)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRef Age(20\u0026ndash;30)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c6\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e31\u0026ndash;40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.482\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.902\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.316\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e11.44\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e41\u0026ndash;50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.464\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.925\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.333\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e11.11\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e51\u0026ndash;60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e9.23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e30.75\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSite Ref(Labial)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c6\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBuccal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.566\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.314\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.517\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3.337\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMouth floor\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.075\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.853\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e25.844\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"7\" rowspan=\"8\"\u003e \u003cp\u003e\u003cb\u003eBi Nucleated\u003c/b\u003e\u003c/p\u003e \u003cp\u003ePresence\u003c/p\u003e \u003cp\u003e(Yes/No)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRef Age(20\u0026ndash;30)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c6\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e31\u0026ndash;40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.923\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.883\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e11.08\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e41\u0026ndash;50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.876\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.825\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.073\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e9.31\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e51\u0026ndash;60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.314\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.189\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.333\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e30.52\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSite Ref(Labial)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c6\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBuccal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.663\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.755\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.213\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.671\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMouth floor\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.152\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.002\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.666\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e13.522\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c6\" namest=\"c2\"\u003e \u003cp\u003e*Adjusted Odds Ratio\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe objective of this study was to determine the cytological changes in oral mucosal cells among smokeless tobacco (naswar) users, examining markers such as micronuclei, nuclear budding (broken-egg nuclei), binucleated cells, and perinuclear halo (indicative of HPV virus), and their distribution across gender and age groups. Our findings showed that 46% of cases exhibited micronuclei, 25% had nuclear buds, 14% had binucleated cells, and 18% had a perinuclear halo. Few studies have explored these aspects.\u003c/p\u003e \u003cp\u003eSmokeless tobacco consumption not only increases the chances of dental caries(\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e) and deterioration of periodontal health(\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e) but also causes cell abnormalities, for instance, binucleation and cellular atypia(\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). Another study reported that the micronuclei count in smokeless tobacco users was higher than in non-smokers/non-users(\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). These findings align with other studies that showed an increased frequency of micronuclei in smokeless tobacco users compared to control groups. Typical cellular changes among tobacco users, including nuclear enlargement indicative of HPV presence, were observed in some buccal smears. Similarly, a local study reported a significant cellular and nuclear diameter increase among naswar users(\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). A study described \"broken egg nuclei\" and binucleated cells, noting that these cells result from chromosome aberrations and failure to complete mitosis(\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). Our observations of cytomorphological changes match previous studies, suggesting a common biological pathway in humans.\u003c/p\u003e \u003cp\u003eOf the 100 participants, 76% of smokeless tobacco users were male, and 24% were female. Most users were in their 5th and 6th decades (51\u0026ndash;60 years), with a mean age of 38 years (SD\u0026thinsp;\u0026plusmn;\u0026thinsp;2.34). These findings are consistent with a study conducted in Nangarhar, which found that 80% of males and 20% of females used naswar(\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). A study revealed that about 15% of males and 10% of females aged 25\u0026ndash;64 years regularly used chewing tobacco or snuff(\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). This demographic trend may be due to similar social and cultural factors, highlighting that our society is male-dominated, with easy access to naswar.\u003c/p\u003e \u003cp\u003eOur results indicate that the most common site for naswar placement was the labial mucosa (47%), followed by the buccal mucosa (41%), with the floor of the mouth being the least common site. This contrasts with a study conducted in the same geographical location that presented the buccal mucosa as the most common site for smokeless tobacco placement(\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). Other studies also predominantly reported buccal mucosa involvement. However, in our study, local smokeless tobacco users believed the labial sulcus played a significant role in sedation, making it the most common site.\u003c/p\u003e \u003cp\u003eNinety-four percent of participants used less than one pack daily, with 48% having used smokeless tobacco for 10\u0026ndash;20 years. These results align with a study of 40 snuff users, where 31 participants used less than one box per day, seven used one box per day, and two used more than one box per day(\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). Our study's setting was private sector, where high socioeconomic individuals seek treatment and have higher education levels, which may explain the lower frequency of naswar use among highly educated individuals.\u003c/p\u003e \u003cp\u003eOral mucosal changes due to snuff usage are well-documented(\u003cspan additionalcitationids=\"CR21\" citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e). It is known that snuff causes damage to the oral cavity, resulting in thick, wrinkled, and discolored mucosa at the site of placement(\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). In our study, 25% of smokeless tobacco users had normal coloration with slight wrinkling, 65% had reddened or yellowish-white wrinkled mucosa, and 10% had heavily wrinkled, thickened mucosa with deep, reddened furrows. It is assumed that longer naswar use leads to more apparent mucosal changes.\u003c/p\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eStrengths and Weaknesses:\u003c/h2\u003e \u003cp\u003eThis study presents several strengths, including its innovative focus on the cytological changes induced by smokeless tobacco (naswar) on oral mucosal cells. Utilizing exfoliative cytology, a non-invasive technique, allows for early detection of potential malignancies, which is patient-friendly and practical for clinical settings. The study's specific focus on a population in Khyber Pakhtunkhwa, Pakistan, provides localized insights into regional practices and their health impacts, contributing valuable information for targeted public health interventions.\u003c/p\u003e \u003cp\u003eHowever, several weaknesses should be noted. Firstly, the study did not conduct a formal sample size calculation, which could affect the statistical power and generalizability of the findings. The use of non-probability sampling and recruitment from a private dental hospital limits the generalizability to the broader population. Additionally, the cross-sectional design precludes longitudinal assessment of the long-term effects of naswar use on the oral mucosa. Furthermore, while necessary, the exclusion criteria may not fully account for all potential confounding factors, such as variations in diet and oral hygiene practices, which could influence the study outcomes. Lastly, the study's scope was limited to cytological changes without investigating potential molecular or genetic alterations associated with naswar use.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eSmokeless tobacco use, specifically habitual naswar chewing, can cause significant changes in the oral mucosa, detectable through exfoliative cytology. The cytological changes observed in this study included micronuclei, nuclear budding (broken eggs), binucleation, and perinuclear halo. These changes were prevalent among men, particularly in their 5th and 6th decades of life. The labial mucosa was the most common site for naswar placement, followed by the buccal mucosa, with varied clinical presentations. To better understand these effects and confirm these findings, further studies with larger sample sizes, standardized parameters, and advanced techniques are needed.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthical Approval \u0026amp; Consent for Participation: \u003c/strong\u003eEthical approval was given by the Ethical Committee, Gandhara University, Peshawar \u0026ndash; Pakistan. The participants also gave written informed consent for participation in the study and data sharing. All the procedures were performed according to the relevant guidelines and regulations \u0026ndash; Declaration of Helsinki.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for Publication: \u003c/strong\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data: \u003c/strong\u003eAll the data generated and analyzed in this study is included in this article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interest:\u003c/strong\u003e No financial or non-financial competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u003c/strong\u003e The authors did not receive any funding to conduct this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; Contribution:\u003c/strong\u003e Study Design \u0026ndash; S. H. D, F. A. K, S. A, Data Collection \u0026ndash; S. H, W. U. N, Analysis \u0026ndash;F. A. K Z. U. H, Data Interpretation \u0026ndash; All authors, Draft the work \u0026ndash; All authors, Revision \u0026ndash; S. H, F. A. K, S. A, A. R.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments:\u003c/strong\u003e NA\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical Trial Number:\u003c/strong\u003e Not applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors Information:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSabreen Hassan\u003csup\u003e1\u003c/sup\u003e, Ayesha Sifat \u003csup\u003e2\u003c/sup\u003e, Mohammad Munib\u003csup\u003e3\u003c/sup\u003e, Saliha Saeed\u003csup\u003e4\u003c/sup\u003e, Waqar U Nisa\u003csup\u003e5\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003eSofia Haider Durrani\u003csup\u003e6\u003c/sup\u003e, Abid Rahim\u003csup\u003e6\u003c/sup\u003e, Naeem Ullah\u003csup\u003e7\u003c/sup\u003e, Saima Afaq\u003csup\u003e2,8*\u003c/sup\u003e, Farhad Ali Khattak\u003csup\u003e1*\u003c/sup\u003e, Zia Ul Haq\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n\u003col\u003e\n\u003cli\u003eKhyber College of Dentistry, Peshawar \u0026ndash; Pakistan\u003c/li\u003e\n\u003cli\u003eKhyber Medical University, Peshawar - Pakistan\u003c/li\u003e\n\u003cli\u003eSwat Medical College, Swat \u0026ndash; Pakistan\u003c/li\u003e\n\u003cli\u003eDental College, HITEC \u0026ndash; IMS, Taxila \u0026ndash; Pakistan\u003c/li\u003e\n\u003cli\u003eBacha Khan Dental College, Mardan \u0026ndash; Pakistan\u003c/li\u003e\n\u003cli\u003eGandhara University, Peshawar - Pakistan\u003c/li\u003e\n\u003cli\u003eSaidu Medical College, Swat - Pakistan\u003c/li\u003e\n\u003cli\u003eDepartment of Health Sciences, University of York, York \u0026ndash; UK\u003c/li\u003e\n\u003cli\u003eInstitute of Public Health and Social Sciences, Khyber Medical University, Peshawar - Pakistan\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003e\u003cstrong\u003e * Corresponding authors:\u003c/strong\u003e\u003c/p\u003e\n\u003col\u003e\n\u003cli\u003e\u003cstrong\u003eFahad Ali Khattak \u003c/strong\u003e(Assistant Professor Biostatistics, Khyber College of Dentistry, Peshawar, Pakistan. https://orcid.org/0000-0002-5933-270X; Email: [email protected])\u003c/li\u003e\n\u003cli\u003e\u003cstrong\u003eSaima Afaq \u003c/strong\u003e(Department of Health Sciences, University of York, York \u0026ndash; UK\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003eEmail: [email protected] , [email protected])\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eTan Y, Wang Z, Xu M, Li B, Huang Z, Qin S et al. 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Cytomorphometric Evaluation of the Epithelial Cells of Buccal Mucosa in Smokeless Tobacco Users. J Datta Meghe Inst Med Sci Univ. 2021;16(1):63\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eParmar D, Sawke N, Sawke G. Cytomorphometric analysis of buccal mucosa cells in tobacco chewers. Astrocyte. 2015;1(4):288\u0026ndash;288. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://go.gale.com/ps/i.do?p=AONE\u0026amp;sw=w\u0026amp;issn=23490977\u0026amp;v=2.1⁢=r\u0026amp;id=GALE%7CA423643891\u0026amp;sid=googleScholar\u0026amp;linkaccess=fulltext\u003c/span\u003e\u003cspan address=\"https://go.gale.com/ps/i.do?p=AONE\u0026amp;sw=w\u0026amp;issn=23490977\u0026amp;v=2.1⁢=r\u0026amp;id=GALE%7CA423643891\u0026amp;sid=googleScholar\u0026amp;linkaccess=fulltext\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-oral-health","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ohea","sideBox":"Learn more about [BMC Oral Health](http://bmcoralhealth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/ohea/default.aspx","title":"BMC Oral Health","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Oral lesions, smokeless tobacco, naswar, cellular alterations, micronuclei, oral cancer","lastPublishedDoi":"10.21203/rs.3.rs-4878492/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4878492/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e Chronic tobacco use, in any form, induces significant cellular alterations in the oral mucosa. This study investigates four distinct cytomorphological changes in oral mucosal cells among smokeless tobacco users, examining their association across different genders and age groups.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMaterials and methods:\u003c/strong\u003e\u003cem\u003e \u003c/em\u003e\u0026nbsp;This cross-sectional study involved collecting mucosal samples from smokeless tobacco (naswar) users through consecutive sampling. The prepared smears were examined for dysplastic changes. Data analysis was performed using SPSS, with Chi-square tests and logistic regression employed to evaluate proportions and associations.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eAmong 100 Naswar users, the labial sulcus mucosa was the most common site affected (47%). The most frequent cytomorphological change was micronuclei (46%), followed by nuclear budding (25%), perinuclear halo (18%), and binucleated cells (14%). In the 51-60 age group, micronuclei (78.9%), nuclear budding (55.3%), binucleation (31.6%), and perinuclear halo (36.8%) were more prevalent (P \u0026lt; 0.005). Gender analysis revealed that micronuclei were more common in females (54.2%) compared to males (43.4%), while nuclear budding was more prevalent in males (27.6%) than females (P \u0026lt; 0.28). Logistic regression indicated that individuals aged 51-60 were more likely to exhibit micronuclei (OR = 1.15, 95% CI: 0.22 to 5.83, P = 0.863) and nuclear budding (OR = 5.34, 95% CI: 9.23 to 30.75, P \u0026lt; 0.05).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e The dysplastic changes observed included micronuclei, nuclear budding, binucleated cells, and perinuclear halo, with micronuclei being the most prevalent. These findings could facilitate the early diagnosis of oral lesions and their timely management in habitual smokeless tobacco users.\u003c/p\u003e","manuscriptTitle":"Cytomorphological Changes of Oral Mucosal Cells Among Smokeless Tobacco Users in Low and Middle-Income Country Settings: Insights from Pakistan","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-09-27 11:39:21","doi":"10.21203/rs.3.rs-4878492/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-10-21T06:51:08+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-10-18T17:01:43+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-10-09T15:26:32+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"10692914915214362447651175302012036449","date":"2024-10-09T10:59:41+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"207873549378897275315034262192544961026","date":"2024-09-18T11:56:35+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-09-07T10:58:49+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2024-09-04T10:27:00+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-08-28T11:37:05+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-08-28T11:34:24+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Oral Health","date":"2024-08-08T06:13:57+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-oral-health","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ohea","sideBox":"Learn more about [BMC Oral Health](http://bmcoralhealth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/ohea/default.aspx","title":"BMC Oral Health","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"62528732-b299-4507-abdf-05e1f72c0cd6","owner":[],"postedDate":"September 27th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-12-30T15:59:17+00:00","versionOfRecord":{"articleIdentity":"rs-4878492","link":"https://doi.org/10.1186/s12903-024-05220-7","journal":{"identity":"bmc-oral-health","isVorOnly":false,"title":"BMC Oral Health"},"publishedOn":"2024-12-23 15:57:06","publishedOnDateReadable":"December 23rd, 2024"},"versionCreatedAt":"2024-09-27 11:39:21","video":"","vorDoi":"10.1186/s12903-024-05220-7","vorDoiUrl":"https://doi.org/10.1186/s12903-024-05220-7","workflowStages":[]},"version":"v1","identity":"rs-4878492","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4878492","identity":"rs-4878492","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}