Oral squamous cell carcinoma (OSCC), one of the most prevalent head and neck cancers, is associated with a number of oral mucosal abnormalities known as Oral Potentially Malignant Disorders (OPMDs).[1] Leukoplakia, erythroplakia, oral submucous fibrosis (OSMF), oral lichen planus, actinic cheilitis, and other lesions and diseases with varying degrees of malignant potential are included in OPMD.[2] Early detection and treatment of these lesions can significantly reduce the chance of invasive oral cancer, improving the patient's prognosis.[3]

Approximately 377,000 new cases and 177,000 deaths from oral cancer are recorded annually, making it a major global public health concern.[4] The significant prevalence of smokeless tobacco products in the social and cultural environment contributes to a disproportionately high illness burden in South Asian nations, including Pakistan, India, Bangladesh, and Sri Lanka.[5] One of the most prevalent cancer-related causes of morbidity and mortality in Pakistan, oral cancer is a common malignancy among men.[6]

Smokeless tobacco includes tobacco products that are chewed or placed in the mouth, cheeks or under the tongue; they are not burned.[7] These are some common forms that are used in Pakistan: Naswar, gutka, tobacco-paan, mawa and betel quid with tobacco.[8] Over 350 million people worldwide are estimated by the World Health Organization to use smokeless tobacco products.[9] South Asia is the region with the highest number of users, and prevalence has been reported to be between 10% and 35% for adults in several countries in the region.[10] National surveys in Pakistan show that 7–12% of adults use smokeless tobacco, with greater rates among men, those living in rural areas, and those with lower socioeconomic level.[11]

A number of factors affect individuals' risk of developing and/or experiencing OPMDs while using smokeless tobacco.[12] These include length and frequency of tobacco use, age at first use, tobacco product used, concurrent alcohol consumption, oral hygiene, dietary deficiencies, socioeconomic risk and genetic predisposition.[13] Previous research has shown that there is a dose–response association and that people with high and regular tobacco consumption have a significantly increased risk of oral precancerous lesions.[14]

Despite a well-established connection between smokeless tobacco use and oral precancerous diseases, OPMDs are frequently asymptomatic in their early stages and are not identified until they have progressed to severe stages. Furthermore, in many parts of Pakistan, there is a dearth of local data about the prevalence and risk factors of OPMDs among tobacco users who do not smoke. Awareness of the potentially fatal consequences of these lesions and identification of modifiable risk factors are crucial for designing screening programs, prevention measures and public health interventions that aim to reduce the incidence of oral cancer.

A survey of the prevalence of OPMDs among people who use smokeless tobacco and the factors associated with their occurrence will yield useful evidence for health care providers, health care officials and policy makers. This knowledge can aid in the early detection of oral cancer, enhance efforts to quit smoking, and ultimately lessen the burden of mouth cancer. Therefore, the purpose of this study was to determine the clinical, behavioral, and demographic risk variables linked to OPMD as well as to evaluate the prevalence of OPD among smokeless tobacco users.

The design of this study was cross-sectional and it took place at Hospital, for a time span of six months from July to December, 2025.

The sample size was determined using OpenEpi version 3.01, for estimation of a population proportion. Based on the findings of another study that found the prevalence of OPMDs among smokeless tobacco users to be 27%, using a 95% confidence interval and an 8% margin of error, a minimum sample size of 140 participants was determined.[15]

Non-probability consecutive sampling technique was used. A consecutive sampling method was used, and all eligible smokers presenting to the outpatient department during the study period were approached and offered consent for inclusion in the study until the desired sample size was obtained.

Participants were those who smoked smokeless tobacco regularly for the past six months or longer and were 18 years old or older. Participants were only those who wished to participate and gave informed consent. Moreover, the participants who could be seen in the study place during data collection were taken into account. Those who had a prior diagnosis of oral cancer or previous treatment for any oral potentially malignant disorder were excluded from the study. Those who were not able to be examined orally or were extremely ill were also excluded. In addition, the patients who didn't sign an informed consent form and who didn't have complete clinical data or a questionnaire were not considered for the final analysis.

Data was gathered using a pre-tested, standardized questionnaire. Sociodemographic information was gathered, including age, gender, education, occupation, monthly income, smokeless tobacco use, duration and frequency of usage, age at first tobacco use, oral hygiene habits, alcohol consumption, and family history of oral cancer. The oral examination was conducted after the interview comprehensively by a trained dental examiner with the help of disposable mouth mirrors, periodontal probes and under adequate illumination with standard precautions for infection control. Oral mucosa was carefully evaluated for the presence of any OPDs such as leukoplakia, erythroplakia, OSMF, oral lichen planus and other suspicious lesions. Diagnoses were made using internationally recognised criteria. Participants who were referred were referred for further evaluation and management as indicated.

The Statistical Package for Social Sciences (SPSS) 26 was used to examine the data. The mean±SD was used to report numerical data such as age, frequency of tobacco use, and duration of smokeless tobacco use. Frequencies and percentages were employed to display qualitative characteristics such gender, education level, kind of smokeless tobacco used, presence of OPMDs, and other categorical data.

The prevalence of OPMDs was determined as the percentage of smokeless tobacco users who had been diagnosed with at least one oral potentially malignant disorder. The Chi-square test or Fisher's exact test, as applicable, was employed to determine associations between OPMDs and categorical risk factors. To determine the independent predictors, binary logistic regression analysis was used, and adjusted odds ratios (AORs) with 95% confidence intervals (CIs) were reported. The statistically significant p-value used was ≤ 0.05

All 140 smokeless tobacco users in the study were smokeless tobacco users. The average age of the participants was 39.8±11.2 years, with the majority being in the age group 31-40 years. The majority of the subjects in this study were males. There were more than half of the participants who lived in rural areas, and secondary-level education was the educational status that was most common among the respondents (Table 1).

Table 1: Socio-Demographic Characteristics of Participants (n = 140)

Naswar was the most popular smokeless tobacco product, followed by gutkas and paan with tobacco, according to a review of tobacco use patterns. Many respondents indicated that they had been using smokeless tobacco for over a decade, and almost half indicated they smoked tobacco more than ten times a day. The average length of time that smokeless tobacco had been used was 8.9 ± 5.4 years (Table 2).

Table 2: Smokeless Tobacco Use Characteristics (n = 140)

More than one-third of the individuals had an oral potentially malignant disorder (OPMD) based on clinical oral examination. Oral submucous fibrosis was the most common lesion observed and was followed by leukoplakia. Oral lichen planus, erythroplakia, and mixed lesions were seen in a smaller number of the participants. Overall, 37.9% of smokeless tobacco users had an OPMD (Table 3).

Table 3: Prevalence and Types of Oral Potentially Malignant Disorders (n = 140)

Bivariate analysis revealed that there were significant relationships between the presence of OPMDs and a number of participant attributes. The male gender, increased number of years of using smokeless tobacco, increased frequency of tobacco use per day, and decreased education level were significantly correlated with a higher prevalence of OPMDs. Oral lesions were most common in smokers who had smoked for more than ten years and smokeless tobacco users who used more than ten times a day (Table 4).

Table 4: Association Between Selected Risk Factors and Presence of OPMDs

A multivariate logistic regression analysis revealed multiple independent risk factors for OPMDs. After adjusting for potential confounders, the strongest predictors were being a current smokeless tobacco user and using it more than 10 times per day, as well as duration of use > 10 years. Lack of formal education and male sex were each significantly associated with increased odds of developing OPMDs independently of each other (Table 5).

Table 5: Binary Logistic Regression Analysis for Predictors of OPMDs

The current study indicated that smokeless tobacco users had a high prevalence of Oral Potentially Malignant Disorders (OPMDs), with leukoplakia and oral submucous fibrosis being the most often seen lesions. This prevalence pattern is in line with the known carcinogenic properties of smokeless tobacco and the chronic irritant effect of smokeless tobacco on oral mucosa, especially in chronic users.[16]

The overall prevalence of OPMDs in the present study was relatively high as compared to several regional studies. The current study's results support those of Sharma et al. (2022), who found a substantial correlation between the burden of OPMDs and tobacco and areca nut product users, with OSMF being the most common disease.[17]

Our findings are also in line with those of Nasir et al. (2023), who discovered that smokeless tobacco use and periodontal and mucosal alterations are significantly correlated in Pakistan, especially for long-term smokeless tobacco users.[18]  They found that both the frequency and duration of use are important factors in oral tissue damage, similar to the risk pattern observed in our study.

Likewise, Ahmad et al. (2023) conducted a study in Karachi that revealed a strong association between OPMDs and naswar usage and a dose-response association between the number of times per day and the severity of OPMDs. This is consistent with our regression analysis finding that longer and more frequent use of smokeless tobacco was independent risk factors for OPMDs.[19]

Male predominance and higher risk in males in our study is consistent with a cross-sectional study on lifestyle factors and OPMDs, which similarly found that there was a higher consumption of tobacco among males in South Asian populations and males were more likely to have OPMDs.[20]

Our prevalence rates exceed some of the global meta-analyses reporting overall prevalence of OPMD among smokeless tobacco users, where rates range from about 10% to 16% by product type and depending on the inclusion of areca nut-containing products. The difference can be attributed to the composition of the product, as naswar and gutka, more popular in Pakistan, contain more nitrosamines (carcinogenic substances) than other products.[15]

A study conducted in Pakistan using gutka as a proxy for smokeless tobacco use found that the severity of oral submucous fibrosis and related lesions is correlated with the duration of use beyond 10 years. This finding supports the strong correlation between prolonged smokeless tobacco use and OPMDs that was found in our study. This could be a sign of the population's cumulative impact from long-term exposure.[21]

There were several limitations to this study that need to be recognized. Due to its cross-sectional design, it is not possible to establish a causal relationship between OPMDs and the use of smokeless tobacco. Conducting a non-probability consecutive sampling may have caused selection bias, which affects external validity. Furthermore, the study was conducted in a single tertiary care institution, which may not be representative of the broader population, particularly in rural community settings where smokeless tobacco use is prevalent. Tobacco use information was self-reported and may be subject to recall and reporting bias. Further, some clinically diagnosed lesions were not confirmed by histopathology, so there was little diagnostic uncertainty. Lastly, molecular and biochemical markers of malignant transformation were not evaluated, and this might have offered a deeper understanding of disease progression.

The present study demonstrates that OPMDs are common among all smokeless tobacco users, oral submucous fibrosis and leukoplakia being the most frequently observed lesions. The duration and frequency of smokeless tobacco use, males, and poor educational attainment were found to be significant risk factors. The findings show a strong dose-response link between the development of OPMDs and long-term usage of smokeless tobacco products. Early detection of those who are at risk and early oral screening are crucial for preventing malignant transformation. The need for specific public health measures, education campaigns, and comprehensive tobacco control policies to curb the prevalence of OPMDs and oral cancer in vulnerable groups is urgent.

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