Abstract
Objectives
To assess the effect of risk factors tobacco, alcohol, and smoking habits in oral precancer patients with epithelial dysplasia status.
Material and methods
The study sample included biopsy proven cases of 29 oral submucous fibrosis (OSMF) and 43 cases of clinical leukoplakia. Histopathological diagnosis was made from formalin fixed paraffin embedded tissues as per WHO criteria. The relevant clinical and demographic details were recorded after interviewing the patients. Risk for tobacco, alcohol and smoking was determined by logistic regression analysis by SPSS software.
Results
Presence of epithelial dysplasia was significantly associated with tobacco in OSMF & both tobacco and smoking habits in leukoplakia. In OSMF tobacco was associated with 14.16-fold (95% CI, 1.36–147.07; p < 0.026) and in leukoplakia tobacco was associated with 4.66-fold (95% CI, 1.00–21.63; p < 0.047) and smoking was associated with 9.20-fold (95% CI, 1.65–51.28; p < 0.011) increased risk of epithelial dysplasia.
Conclusion
Tobacco consumption was independent risk factor for epithelial dysplasia in OSMF and both tobacco and cigarette smoking were independent factors for epithelial dysplasia in leukoplakia.
Keywords: Oral precancer, Epithelial dysplasia, OSMF, Leukoplakia, Tobacco
Introduction
Oral habits like tobacco chewing in the form of betel quid areca nut, smoking and alcohol consumption are most prevalent in Indian population. India accounts for 86% of the world's oral cancer cases, as per the data from National Institute of Public Health (February 2011). Several factors influence the epithelial dysplasia status; duration of the lesion, age of patient, intra oral site, risk habit and infection with human papillomavirus (HPV) and Candida. It is likely that as the lesion is present for years and decades there could be changes to dysplasia status, some worsening and other resolving.1 The presence of epithelial dysplasia is one of the most important predictors of malignant development in pre-malignant lesions.2 Oral submucous fibrosis (OSMF) and leukoplakia are clinically distinct precancerous lesions that precede the development of oral cancer.3 Thus, the challenge within the field of oral precancer is to predict which lesions will eventually develop into carcinoma and what are the risk factors that may be involved in development of epithelial dysplasia.
The aim of this study was to assess the effect of three important risk factors; tobacco, alcohol, and smoking habits in oral precancer patients with histological proven epithelial dysplasia.
Material and methods
Tissue biopsies were taken from cases of 29 OSMF and 43 clinical leukoplakia from the Departments of Oral and Maxillofacial Surgery and Otolaryngology after obtaining the Institutional Ethical approval and informed written consent from the patients from year 2007 to year 2011. The relevant clinical and demographic details were recorded after interviewing the patients.
Histopathological examination
All oral tissues were fixed in 10% neutral buffered formalin and processed for histopathological examination as per standard procedure. 5 μm thick sections were cut and stained with haematoxylin and eosin (H&E). Sections were reviewed by two independent pathologists and histological diagnosis was made as per WHO criteria.
Statistical analysis
Statistical analysis was performed using version 17.0 SPSS software for windows (SPSS, INC, Chicago, IL). For assessing proportional data, chi-square test was carried out. Logistic regression was applied to evaluate hazard ratios for the dysplasia. Odds ratios (OR) with 95% confidence interval (95% CI) and p values were calculated. For all the tests, a p-value <0.05 was considered statistically significant.
Results
Clinicopathological characteristics of patients
The study population included 72 cases of oral precancer which included 29 cases of OSMF and 43 cases of oral leukoplakia as shown in Table 1. Epithelial dysplasia was present in 62.07% (18/29) cases of OSMF and 76.74% (33/43) cases of leukoplakia. Buccal mucosa was the most common site for OSMF and leukoplakia. In OSMF tobacco 79.31% (23/29) using habit was most prevalent where as in leukoplakia tobacco and smoking, both habits 58.14% (25/43) were prevalent.
Table 1.
Clinical characteristics of patients.
| Characteristics | OSMF (n = 29) | Leukoplakia (n = 43) |
|---|---|---|
| Age | ||
| <35 | 13 | 15 |
| ≥35 | 16 | 28 |
| Sex | ||
| Male | 19 | 35 |
| Female | 10 | 8 |
| Topological site | ||
| Tongue | 1 | 7 |
| Buccal mucosa | 23 | 28 |
| Lip | 1 | 2 |
| Palate | 3 | 1 |
| Retromolar region | 1 | 1 |
| Buccal vestibule | 0 | 2 |
| Gingivobuccal sulcus | 0 | 2 |
| Dysplasia | ||
| Present | 18 | 33 |
| Absent | 11 | 10 |
| Tobacco | ||
| Present | 23 | 25 |
| Absent | 6 | 18 |
| Alcohol | ||
| Present | 8 | 20 |
| Absent | 21 | 23 |
| Smoking | ||
| Present | 11 | 25 |
| Absent | 18 | 18 |
Association of clinical characteristics of patients with dysplasia in OSMF
Epithelial dysplasia status was significantly (p < 0.010) associated with presence of tobacco habit in OSMF as shown in Table 2. No association was found with epithelial dysplasia status in OSMF with age, sex, alcohol and smoking habits.
Table 2.
Association of clinical characteristics of patients with epithelial dysplasia in OSMF.
| Characteristics | OSMF with epithelial dysplasia (n = 18) | OSMF without epithelial dysplasia (n = 11) | p-Value |
|---|---|---|---|
| Age | |||
| <35 | 8 | 5 | 0.958 |
| ≥35 | 10 | 6 | |
| Sex | |||
| Male | 13 | 6 | 0.331 |
| Female | 5 | 5 | |
| Tobacco | |||
| Present | 17 | 6 | 0.010 |
| Absent | 1 | 5 | |
| Alcohol | |||
| Present | 13 | 8 | 0.976 |
| Absent | 5 | 3 | |
| Smoking | |||
| Present | 10 | 8 | 0.335 |
| Absent | 8 | 3 | |
Association of clinical characteristics of patients with dysplasia in leukoplakia
Epithelial dysplasia status was significantly associated with presence of tobacco (p < 0.039) and smoking (p < 0.005) habits in leukoplakia as shown in Table 3. No association was found with epithelial dysplasia status in leukoplakia with age, sex and alcohol habit.
Table 3.
Association of clinical characteristics of patients with dysplasia in leukoplakia.
| Characteristics | Leukoplakia with epithelial dysplasia (n = 33) | Leukoplakia without epithelial dysplasia (n = 10) | p-Value |
|---|---|---|---|
| Age | |||
| <35 | 12 | 3 | 0.711 |
| ≥35 | 21 | 7 | |
| Sex | |||
| Male | 27 | 8 | 0.897 |
| Female | 6 | 2 | |
| Tobacco | |||
| Present | 11 | 7 | 0.039 |
| Absent | 22 | 3 | |
| Alcohol | |||
| Present | 15 | 5 | 0.801 |
| Absent | 18 | 5 | |
| Smoking | |||
| Present | 23 | 2 | 0.005 |
| Absent | 10 | 8 | |
Logistic regression analysis of risk factors in precancer with dysplasia status
Risk with age, sex, tobacco, alcohol and smoking habits for epithelial dysplasia was evaluated by univariate logistic regression and found that tobacco and smoking habits were associated with 4.43-fold (95% CI, (1.47–12.75); p < 0.008) and 4.96-fold (95% CI, 1.56–15.67; p < 0.006) increased risk of epithelial dysplasia in precancer, respectively as shown in Table 4. In OSMF tobacco was associated with 14.16-fold (95% CI, 1.36–147.07; p < 0.026) and in leukoplakia tobacco was associated with 4.66-fold (95% CI, 1.00–21.63; p < 0.047) and smoking was associated with 9.20-fold (95% CI, 1.65–51.28; p < 0.011) increased risk of epithelial dysplasia.
Table 4.
Logistic regression analysis of risk factors with dysplasia status in OSMF, leukoplakia and precancer.
| Variables | OR (95% CI) | p-Value |
|---|---|---|
| OSMF (n = 29) | ||
| Age | 1.04 (0.23–4.70) | 0.958 |
| Sex | 0.46 (0.09–2.22) | 0.335 |
| Tobacco | 14.16 (1.36–147.07) | 0.026 |
| Alcohol | 1.02 (0.19–5.50) | 0.976 |
| Smoke | 2.13 (0.42–10.78) | 0.359 |
| Leukoplakia (n = 43) | ||
| Age | 0.75 (0.16–3.45) | 0.712 |
| Sex | 0.88 (0.14–5.29) | 0.897 |
| Tobacco | 4.66 (1.00–21.63) | 0.047 |
| Alcohol | 0.83 (0.20–3.43) | 0.801 |
| Smoke | 9.20 (1.65–51.28) | 0.011 |
| Precancer (n = 72) | ||
| Age | 0.95 (0.33–2.71) | 0.929 |
| Sex | 0.55 (0.17–1.69) | 0.298 |
| Tobacco | 4.43 (1.47–12.75) | 0.008 |
| Alcohol | 1.04 (0.36–2.98) | 0.929 |
| Smoke | 4.96 (1.56–15.67) | 0.006 |
Discussion
The present study evaluated the risk factors that were responsible for presence of epithelial dysplasia in precancer. The study samples included only biopsy proven cases of OSMF and leukoplakia with and without epithelial dysplasia. In this study we observed that tobacco consumption was found to be an independent risk factor for OSMF patients with epithelial dysplasia. The relative risk (OR) for having epithelial dysplasia in OSMF for tobacco was 14.16. Ahmad et al4 found that 152 out of 157 patients used gutka and other areca nut products. Tobacco contains up to 50 potential carcinogens, such as nitrosamines and polycyclic aromatic hydrocarbons. Some of them may cause mutations of the p53 tumour-suppressor gene or other genes that disrupt cell-cycle regulation and modulation of the immune systems.5 We found that tobacco was strongly associated with both OSMF and leukoplakia. This study showed that the risk of OSMF at each exposure level of tobacco was stronger than that of leukoplakia. C H Lee et al3 also suggested that tobacco in the form of betel quid chewing was strongly associated with both these oral diseases, the attributable fraction of leukoplakia being 73.2% and of OSMF 85.4%. They suggested that although betel quid chewing was a major cause for both leukoplakia and OSMF, its effect might be different between the two diseases.
Cigarette smoking has an important role in the development of epithelial dysplasia in oral leukoplakia. It was found that tobacco and smoking habits were the risk factors associated with epithelial dysplasia in leukoplakia patients. Kulasegaram et al6 found the relative risk of having a dysplastic lesion for smokers compared with non-smokers, or ex-smokers for more than 10 years, was 7.00. We found the relative risk for having epithelial dysplasia in precancer for smoking was 9.20 and for tobacco it was 4.66.
We did not find significant risk for alcohol consumption for epithelial dysplasia in OSMF and leukoplakia. Other studies also did not find overall increased risk with alcohol.3,6 Although ethanol has been recognized as a solvent that may damage the oral cells and increase the mucosal penetration of certain oral carcinogens,7 the role of alcohol drinking in the development of precancer is still unclear.
In summary tobacco was independent risk factor for epithelial dysplasia in OSMF and both tobacco and cigarette smoking were independent factors for epithelial dysplasia in leukoplakia.
Conflicts of interest
All authors have none to declare.
Acknowledgement
Authors gratefully acknowledge the financial support from Indian council of medical research (ICMR) New Delhi, India.
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