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The prevalence of oral squamous cell carcinoma with oral submucous fibrosis

1 Oral Medicine and Radiology Department, Nair Hospital Dental College, Mumbai, Maharashtra, India
2 Oral Medicine and Radiology Department, Government Dental College, Aurangabad, Maharashtra, India
3 Department of Dentistry, JJ Hospital, Mumbai, Maharashtra, India
4 Pediatric and Preventive Dentistry Department, ITS Dental College, Greater Noida, Uttar Pradesh, India

Date of Submission06-Sep-2019
Date of Decision17-Nov-2019
Date of Acceptance07-Jan-2020
Date of Web Publication03-Nov-2020

Correspondence Address:
Mohd Saalim,
Oral Medicine and Radiology Department Nair Hospital Dental College, Mumbai, Maharashtra
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jcrt.JCRT_719_19

 > Abstract 

Objective: The objective of the study was to find out the prevalence of oral squamous cell carcinoma (OSCC) with oral submucous fibrosis (OSF) in patients with OSF.
Materials and Methods: Of 48,757 patients, we found 300 OSF subjects. Three hundred patients of OSF were checked for OSCC. Both OSF and OSCC with OSF (OSCCwOSF) were diagnosed histopathologically. The prevalence of OSCCwOSF was calculated. Descriptive analysis was done. Chi-square test and t-test were calculated for proportions and mean, respectively, to check any difference among OSF and OSCCwOSF groups. Age-specific relative risk was calculated in OSF and OSCCwOSF groups. Multiple logistic regression analysis was done among odd ratios of the different variable between OSF and OSCCwOSF groups.
Results: The prevalence of OSCCwOSF among OSF was 13.7% over a period of 1 year. The mean age of OSCCwOSF group was 43.95 ± 10.22 years in comparison to the OSF group that was 35.51 ± 11.26 years (P < 0.00). The mean habit duration was significantly less in the OSF group when compared to OSCCwOSFgroup for mishri (P = 0.002). Age-specific adjusted relative risk of OSCC in OSF patient increases from 0.33 (18–34 years) to 3.86 (≥65 years)
Conclusion: It could be concluded that a 13.7% prevalence rate of OSCCwOSF in OSF patients should alert the clinician. Clinicians should, therefore, anticipate OSSC in OSF patients. This awareness could lead to the early diagnosis and management of such OSCC.

Keywords: Areca nut, oral potentially malignant disorders, oral squamous cell carcinoma with oral submucous fibrosis, oral squamous cell carcinoma, oral submucous fibrosis

How to cite this URL:
Saalim M, Sansare K, Karjodkar FR, Johaley S, Ali IK, Sharma SR, Mehra A, Rahman B. The prevalence of oral squamous cell carcinoma with oral submucous fibrosis. J Can Res Ther [Epub ahead of print] [cited 2021 Nov 28]. Available from: https://www.cancerjournal.net/preprintarticle.asp?id=299889

 > Introduction Top

Oral potentially malignant disorders (OPMDs) are the disorders of oral and oropharyngeal mucosa that are more predisposed to malignant transformation.[1] In Southeast Asian countries, oral submucous fibrosis (OSF) is a well-recognized OPMD.[2] OSF is a chronic debilitating disease of the oral cavity that presents with a burning sensation, blanching of the oral mucosa, submucosal fibrosis, restricted mouth opening, etc., and is most commonly associated with the habit of areca nut chewing. OSF is a disease that has a high risk of malignant transformation.

OSF is one of the common OPMDs; it is, therefore, possible that oral squamous cell carcinoma (OSCC) would be present in OSF patients. In India oral cancer contribute to over 30% of total reported cancer.[3] Oral cancer is one of the main causes of death among oral diseases.[4] Globally, oral cancer is recognized as the sixth most common cancer with an annual incidence of over 300,000 cases, of which 62% arise in developing countries.[5] OSCC ranks among the top three cancers in India and is the eighth most common cancer worldwide.[6] According to the GLOBOCAN 2018, in India, the prevalence of oral cancer is 5.6% and it is the second most common cancer after breast cancer.[7]

Paymaster in 1956 for the first time postulated the precancerous nature of OSF. Later Gupta et al.,[8] Pindborg et al.,[9] and Murti et al.[10] reported malignant transformation rate of 2.3%, 4.5%, and 7.6%, respectively, with an increasing rate chronologically. Lian et al.[11] reported 8.63% malignant transformation of OSF in the Taiwan population. In mainland China, two case–control studies [12],[13] reported 11.02%and 15% of OSF patients advancing into oral cancer. There seems to be no consensus on the malignant transformation rate of OSF, varying from 2.3% to 15%. Literature is devoid of the prevalence of OSCC in the OSF population. Moreover, the prevalence rate of OSCC in OSF in a high-density population like India has not been investigated.

Knowledge of the prevalence of OSCC in OSF will help the clinician in anticipating OSCC in OSF cases and therefore creating awareness. It could also be of use in subjecting such OSCC to early treatment. Given this background, it was decided to assess the prevalence of OSCC in the OSF population.

 > Materials and Methods Top

A pilot study was conducted to find the prevalence of OSCC in OSF cases for 2 months. The Z-statistic was 1.96 for 95% confidence interval (CI), 10% maximum allowable risk, and the prevalence of OSCC in OSF from the pilot study was 0.08 (8%). The minimum sample size calculated was 282. It was, therefore, decided to begin the study with a sample size of 300 patients. The study was conducted in accordance with the guidelines of the Declaration of Helsinki and was approved by the Institutional Ethics Committee (IEC Project No. EC-55/DOMR-26ND/2017). All 300 patients had given their voluntary consent to participate in the study. Every new consecutive case of OSF reported to the oral medicine unit from February 1, 2017 to February 28, 2018, was selected by a single examiner with more than 10 year of experience in oral mucosal lesions. The diagnosis of OSF was based on the presence of one or more of the following criteria recommended at the workshop held in Kuala Lumpur, Malaysia.[14] Palpable fibrous bands, mucosal texture feels tough and leathery, and blanching of mucosa together with histopathological features were consistent with OSF (atrophic epithelium with loss of rete ridges and juxta-epithelial hyalinization of lamina propria).

A total of 48,757 patients were examined. These patients belonged to the lower socioeconomic strata and attended the dental outpatient department at a major tertiary care hospital. A combined 312 patients of OSF and OSCC with OSF (OSCCwOSF) were identified when examining this cohort. All clinically diagnosed patients of OSF and OSCCwOSF were biopsied and included in the study only after histopathological confirmation. Patients reported as OSF with dysplasia or OSF with carcinoma in situ (12 patients), patients with any other malignant lesion of the jaw or of any other organ of the body metastasizing to the oral cavity, OSF with any other concurrent oral mucosal lesion, and pregnant patients were excluded from the study. The included patients were then divided into two groups: the OSF group and the OSCCwOSF group. Descriptive data such as age, sex, and various habit duration were retrieved for the two groups. The percentage of patients in OSCCwOSF group among the OSF group was considered as the prevalence of OSCC in OSF.

Data analysis

Demographic factors including age, sex, and habit history such as habit duration and comorbidity index were compared between OSF and OSCCwOSF groups. The prevalence of OSCC in the OSF population was calculated. OSF was clinically classified according to Haider et al.[15] Oral cancer was classified according to the TNM staging developed by the American Joint Committee on Cancer and International Classification of Disease, 10 Revision, Clinical Modification (ICD-10-CM). Charlson Comorbidity Index (CCI) was calculated for OSF and OSCCwOSF groups; the score for CCI was grouped as 0, 1, 2, and ≥3. A high score of CCI showed higher comorbidity.[16]

Chi-square test was used to find any differences in sex and comorbidity in OSF and OSCCwOSF groups. Student's t-test was used to assess any significant difference between mean age and mean habit duration of OSF patients and OSCCwOSF patients. Age-specific relative risk was calculated in the OSF and OSCCwOSF groups. Multiple logistic regression analysis was done to assess odd ratios for different variables in OSF and OSCCwOSF groups. P<0.05 was considered significant. Confounding bias was managed by multiple logistic regression analysis with stepwise backward elimination, and only significant results are presented.

Statistical Package for the Social Sciences (SPSS, SPSS, Inc., Chicago IL, US) software, version 17.0 was used for the statistical analysis.

 > Results Top

Of 48,757 patients, 300 OSF patients were identified which fulfilled the selection criteria. Of these 300 OSF cases, 41 cases were of OSCCwOSF. Stage A OSF patients were more prevalent followed by Stage B and among OSCC Stage 3 followed by Stage 2 [Table 1]. The prevalence of OSCC in the OSF population was 13.7% over a period of 1 year. In the OSF group, 224 patients were male and 35 were female with a male-to-female (male:female) ratio of 6.4:1; in the OSCCwOSF group, 36 patients were male and 5 were female with a male:female ratio of 7:2. The mean age of OSF group was 35.51 ± 11.26 years (age range 15–69 years) in comparison to OSCCwOSF group which was 43.95 ± 10.22 years (age range 26–71 years). OSF is seen in lower age group in comparison to OSCCwOSF group with a P < 0.00.
Table 1: Staging of oral submucous fibrosis and oral squamous cell carcinoma with oral submucous fibrosis patients

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In OSF group, 14 patients (8 hypertensive, 4 diabetic, and 2 asthmatics) and, in OSCCwOSF, three patients (all were diabetic) were with comorbidity. No significant difference was found in CCI between the two groups (P = 0.55). OSCC cases were classified according to the ICD-10-CM. Most of the cases were aggregated in the Code C06 section that states malignant neoplasm of other and unspecified part of the mouth [Table 2].
Table 2: Site distribution of oral squamous cell carcinoma with oral submucous fibrosis according to the International Classification of Disease, 10 Revision, Clinical Modification

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Comparison of habit duration between OSF and OSCCwOSF groups is presented in [Table 3]. The mean habit duration was significantly less in the OSF group when compared to OSCCwOSF group for mishri (P = 0.002). Age-specific adjusted relative risk of OSCC in OSF patient increased from 0.33 (18–34 years) to 3.86 (≥65 years), as shown in [Table 4]. Frequency of habit, age when habit started, age when habit discontinued, keeping duration in the mouth, spit after chewing, swallow after chewing, overnight quid keeping habit and association of these parameters with each habit, family history of cancer, spicy versus non-spicy food habit, impacted versus erupted third molar, and the presence of sharp cusp or root piece all these factors were recorded in the study. However, the association in these factors and OSCC was not significant, and therefore, the data were not presented.
Table 3: Comparison of habit duration between oral submucous fibrosis and oral squamous cell carcinoma with oral submucous fibrosis group

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Table 4: Age specific adjusted relative risk of oral squamous cell carcinoma in oral submucous fibrosis patient

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Multiple logistic regression analysis was done to determine odds ratio for different variables among OSF and OSCCwOSF groups [Table 5]. Odds of having OSCC among OSF is 41.59 times with increasing age from the third decade to the seventh decade (95% CI being 2.69–643.13 with a significant P < 0.05).
Table 5: Multiple logistic regression analysis of odd ratio of different variable in oral submucous fibrosis and oral squamous cell carcinoma in oral submucous fibrosis group

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 > Discussion Top

The Indian subcontinent is known for its high incidence of both OSF and oral cancer because of the high prevalence of habit of different preparation of tobacco and areca nut.[17],[18] The mucosa that has OPMDs is more predisposed to malignant transformation in comparison to the normal mucosa.[1] OPMDs have a high rate of malignant transformation (7%–30%).[19] The results of this study suggest a 13.7% of prevalence rate of OSCC in OSF cases for a period of 1 year. Since no data are available on the prevalence of OSCC in OSF patients, we, therefore, compare our data with that of malignant transformation rate of OSF. Liu et al.[13] (2015) reported 15% and Lian et al.[11] (2013) reported 11.02% of OSF cases proceeding to the oral cancer. According to a recent study, Chuang et al,[20] the annual malignant transformation rate of OSF is 8.6/1000.

These studies suggest that the malignant transformation rate of OSF has increased in recent years. In this study, the prevalence rate was higher than most of the earlier malignant transformation rate. It is, therefore, postulated that the increased prevalence of OSCC in OSF cases may indicate a higher rate of malignant transformation. The increased prevalence of OSCC in OSF could be attributed to the easy availability of tobacco and areca nut product, nominal cost, colorful attractive packaging, and low socioeconomic status. Promotion of these products as breath fresheners and distribution of areca nut as a social, cultural, and religious practice compounded by poor awareness regarding OSCC in OSF cases could also be the reasons for the increased prevalence.

In our study, OSF was predominantly found in males. This result is consistent with the results of previous studies.[21],[22] Chaturvedi et al.[22] (2013) reported 45.11 years' mean age of OSCCwOSF in comparison to the oral cancer cases without OSF that was 50.07 years. In our study, patients of OSCCwOSF had a mean age of 43.95 years which is comparable to that reported by Chaturvedi et al.[22] Following the ICD-10-CM classification, the most prevalent site for OSCC in this study was other and unspecified parts of the mouth (ICD C06) followed by the tongue and lip. This result is consistent with the result of Yang et al.,[23] 2017. In our study, the majority of the patients of OSCCwOSF involved the bucco-alveolo-vestibulo-gingival complex. This is plausible because OSF primarily affects the buccal mucosa. Moreover, OSCC in South East Asian region commonly involves the buccal mucosa. The ICD-10-CM coding does not include lesions involving sites, especially the buccal mucosa, alveolar mucosa, and vestibular mucosa. It is, therefore, proposed to revise the ICD-10-CM classification to include these regions.

The mean habit duration was significantly less in the OSF group (5.91 years) when compared to the OSCCwOSF group (32 years) for mishri habit [P = 0.002 – [Table 3]. It could be inferred that malignant transformation increases in OSF patients who used mishri (burnt tobacco) for longer duration. It can be hypothesized that burnt tobacco has more carcinogenic potential than tobacco. This result should be considered with caution because the number of patients in the mishri group was underrepresented. Therefore, when a patient is counseled to quit habit, there is a need to counsel regarding quitting of all other habits. There could be a possibility that some patients quit areca nut chewing and continue with other habits or start an alternative habit. Such patients are at higher risk for developing oral cancer because of finally leading to multiple habits. However, this hypothesis needs to be tested in further studies. In this study, individual habit was considered for the analysis because many patients had mixed habits with various combinations of habits which made the comparison of combination of habits difficult.

In the current study, age-specific relative risk of developing OSCC in OSF patients is higher with increasing age. This result was consistent with the result of a recent study by Yang et al.,[23] 2017. It means that supportive and nutritional care should be provided from the third decade of life because as age advances the relative risk increases approximately 12-folds from the third to seventh decade. Therefore, it is advisable to prevent the development of oral cancer in OPMDs because oral cancer treatment results in high morbidity and also shows recurrence. However, at this moment, there are no interventions available to prevent the malignant transformation of OSF, and increasing awareness seems to be the only alternative.

 > Conclusion Top

It could be concluded that 13.7% prevalence rate of OSCC in OSF patients should alert the clinician to anticipate OSSC in OSF patients. This awareness could lead to early diagnosis and management of such OSCC. Clinicians could also make attempt to control the development of OSF and its malignant conversion through counseling.

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Conflicts of interest

There are no conflicts of interest.

 > References Top

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  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]


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