Correlation of a new binary system in grading of oral leukoplakia for its prediction of malignant transformation - A retrospective record-based study

NC Sangamesh; Vinay Suresan; KC Vidya; Dhirendra K Singh

doi:10.4103/jiaomr.jiaomr_52_22

ORIGINAL ARTICLE

Year : 2022 | Volume : 34 | Issue : 4 | Page : 418-422

Correlation of a new binary system in grading of oral leukoplakia for its prediction of malignant transformation - A retrospective record-based study

NC Sangamesh¹, Vinay Suresan², KC Vidya³, Dhirendra K Singh⁴
¹ Department of Oral Medicine and Radiology, Kalinga Institute of Dental Sciences, KIIT DU, Bhubaneswar, Odisha, India
² Department of Public Health Dentistry, Kalinga Institute of Dental Sciences, KIIT DU, Bhubaneswar, Odisha, India
³ Department of Oral and Maxillofacial Surgery, Kalinga Institute of Dental Sciences, KIIT DU, Bhubaneswar, Odisha, India
⁴ Department of Periodontolgy, Kalinga Institute of Dental Sciences, KIIT DU, Bhubaneswar, Odisha, India

Date of Submission	17-Feb-2022
Date of Decision	18-Jul-2022
Date of Acceptance	28-Nov-2022
Date of Web Publication	09-Dec-2022

Correspondence Address:
N C Sangamesh
Professor and Head Vice Principal, Department of Oral Medicine and Radiology, Kalinga Institute of Dental Sciences, KIIT DU, Bhubaneswar, Odisha
India

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/jiaomr.jiaomr_52_22

Abstract

Introduction: Oral Leukoplakia is a premalignant lesion with an increased risk of developing oral cancer when the lesion is non-homogeneous. There is a need to validate clinical presentations of a commonly occurring Leukoplakia lesion and its probability of dysplastic changes over some time. Aim: To correlate the Diagnostic accuracy of clinical lesion diagnosed as Leukoplakia and the presence or absence of dysplasia through its histopathological correlation. Materials and Methods: This study gathered data retrospectively during 2016–2021 with an initial diagnosis of oral Leukoplakia. A set of 611 slides were included in the study that was signed out as oral Leukoplakia. We tested the hypothesis that a binary grading system categorizes lesions as “presence” or “absence” of oral epithelial dysplasia. A logistic regression analysis was used in predicting the presence of dysplasia among the various clinical criteria. Results: Most of the mild dysplasia was reported in the buccal mucosa (n = 195; 31.91%), followed by 6 (0.98%) cases in the vestibule. A mean age of 32.33 ± 7.0 was observed for severe dysplasia. A statistically significant relationship between the risk estimates for the clinical diagnosis and dysplasia was noted for all the lesion types. Conclusion: The study concludes that the clinical presentation of a lesion can predict the underlying dysplastic changes, and mixed red and white lesions with growth possess the highest risk of malignant transformations.

Keywords: Histopathological correlation, oral epithelial dysplasia, oral leukoplakia, precancerous conditions
Key Message: The current study derives an inference that the clinical presentation of a lesion can predict the underlying dysplastic changes. Therefore, this necessitates the added responsibility of the clinicians to screen the patients carefully, encompass oral pre-malignant lesions, and advise appropriate histopathological investigations.

How to cite this article:
Sangamesh N C, Suresan V, Vidya K C, Singh DK. Correlation of a new binary system in grading of oral leukoplakia for its prediction of malignant transformation - A retrospective record-based study. J Indian Acad Oral Med Radiol 2022;34:418-22

How to cite this URL:
Sangamesh N C, Suresan V, Vidya K C, Singh DK. Correlation of a new binary system in grading of oral leukoplakia for its prediction of malignant transformation - A retrospective record-based study. J Indian Acad Oral Med Radiol [serial online] 2022 [cited 2023 Jan 28];34:418-22. Available from: http://www.jiaomr.in/text.asp?2022/34/4/418/363037

Introduction

Oral epithelial dysplasia (OED), not associated with any specific clinical appearance, is a term assigned to the histopathological changes associated with an increased risk of malignant transformation.^[1] These potentially malignant lesions show variable clinical presentation.^[1],[2],[3] Oral carcinomas are associated with leukoplakic lesions. When diagnosed, it showed that oral pre-cancerous lesions preceded about 80% of oral cancers.^[4],[5],[6]

Oral Leukoplakia is a premalignant lesion that has long been considered to confer an increased risk for the development of oral cancer when the lesion is non-homogeneous.^[7],[8] Among these, nodular Leukoplakia is considered a high-risk precancerous lesion, and homogeneous and ulcerated Leukoplakia is a moderate-risk precancerous lesion.^[9] In general, it is more or less accepted as an overall statement that approximately 5% of all leucoplakias' will transform into cancer in an average period of 5 years.^[10],[11]

The diagnosis of “Leukoplakia” is never used without the histopathological qualifiers “with dysplasia” or “without dysplasia.” The problems in evaluating the significance of epithelial dysplasia arise from a lack of clarity in the established clinical criteria for predicting malignant potential.^[12],[13] There is little conclusive data available about the clinical criteria based on which OED can be diagnosed without histopathological aid. Hence, this investigation was to correlate the Diagnostic accuracy of clinical lesion diagnosed as Leukoplakia and the presence or absence of dysplasia through its histopathological correlation.

Methodology

This study was conducted and reported by the STARD 2015 Statement for reporting diagnostic accuracy studies.^[14] Institutional ethical committee approval was taken (No: KIIT/KIMS/IEC/117/2019). The research was conducted by the guidelines of the Helsinki declaration protecting the subjects' autonomy and confidentiality.

This study gathered data retrospectively from the archives of the Department of Oral Medicine and Radiology, Kalinga Institute of Industrial Technology, Bhubaneswar, Odisha. Sequential cases diagnosed at the original sign-out report during 2016–2021 with an initial diagnosis of oral Leukoplakia were retrospectively reviewed. Eligibility criteria for inclusion were those with available histologically confirmed diagnoses and those with a computerized digital file. A set of 611 slides were included in the study, originally signed out as oral Leukoplakia.

Demographic information of age at the time of diagnosis, gender, site, and clinical presentation of the lesion was recorded. The specific site of occurrence of the lesion was topographically coded according to the International Classification of Diseases-9 (ICD-9) as having occurred in the gingiva, tongue, floor of the mouth, vestibule, retromolar area, palate, buccal mucosa, or lips.

G*Power Software Version 3.1.9.7 was used for sample size calculation.

Input: Tail (s) = Two

|Δ intercept| = 1.3

α err prob = 0.05

Power (1-β err prob) = 0.95

Allocation ratio N2/N1 = 1

Std dev residual σ = 2

Std dev σ_x1 = 4

Std dev σ_x2 = 3

Mean μ_x1 = 5

Mean μ_x2 = 7

Output: Noncentrality parameter δ = 3.6111623

Critical t = 1.9642709

Df = 552

Sample size group 1 = 278

Sample size group 2 = 278

Total sample size = 556

Actual power = 0.9500057

The minimal sample size derived was 556.

Four observers scored the slides. All these were academic staff, Department of Oral and Maxillofacial Pathology, with long experience grading oral dysplastic lesions. No calibration exercises were attempted. Each slide was labeled with a number. No clinical information or patient data were provided with the biopsies. A score sheet was designed for recording grading to aid systematic analysis. The scores for each slide were made after a consensus score was reached on the degree of dysplasia amongst all four oral pathologists. The examiners demonstrated an inter-examiner reliability kappa value of 0.91, indicating very high reliability.

The clinical diagnosis of oral Leukoplakia was based on the criteria provided by Axell T et al.,^[15] Clinical; a distinction was made between homogeneous and non-homogeneous Leukoplakia; the latter includes erthyroleukoplakia, nodular, exophytic, and proliferative verrucous types. The clinical pictures of all the lesions were graded based on the architecture and cytology criteria for grading epithelial dysplasia according to the WHO classification^[16] into the presence or absence of the criteria [Table 1]. The histopathological features (mild, moderate, severe, and carcinoma-in-situ), as given by the pathologist from paraffin sections of pre-treatment biopsies, were blindly and retrospectively re-examined by an expert oral pathologist. The association between the clinical outcomes and the histological assessment scoring was examined.

Table 1: WHO classification 2005 for architecture and cytology criteria for grading epithelial dysplasia

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We tested the hypothesis that a binary grading system categorizes lesions as “presence” or “absence” of oral epithelial dysplasia. Based on these parameters, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, and prevalence were calculated for the clinical criteria against the presence or absence of dysplasia. A logistic regression analysis was used in predicting the presence of dysplasia among the various clinical criteria. SPSS (Statistical Package for Social Sciences) version 22 was used. A P value lesser than or equal to 0.05 was considered significant.

Results

Demographic characteristics

The demographic characteristics of the study population included the overall presentation of the lesions, the mean age at which the dysplastic lesions were commonly noted, and the gender predilection of the lesions. Most of the mild dysplasia was reported in the buccal mucosa (n = 195; 31.91%), followed by 6 (0.98%) cases in the vestibule. There were 81 (13.2%) cases of moderate dysplasia in the buccal mucosa and 12 (1.96%) cases in the tongue. Severe dysplasia was found among 18 (2.94%) cases in the buccal mucosa. There were 54 (8.83%) cases of carcinoma in situ in the buccal mucosa and 12 (1.96%) cases in the retro-molar area. Dysplasia was not present in 222 (36.33%) cases reported in the buccal mucosa and 6 (0.98%) cases reported in the vestibule. A statistically significant difference in the presentation of the lesions was noted (p < 0.0001) [Table 2].

Table 2: Demographic distribution

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A mean age of 38.96 ± 12.5 was reported for mild dysplasia, 42.94 ± 12.2 for moderate dysplasia, 32.33 ± 7.0 for severe dysplasia, 52.09 ± 8.9 for carcinoma in situ and 39.59 ± 14.2 for no dysplasia. A statistically significant difference was noted (p < 0.0001).

Dysplasia in buccal mucosa was reported among 339 (56.5%) males and 9 (1.5%) females. 12 (2%) males reported dysplasia in the tongue. Dysplasia in the vestibule was reported among 6 (1%) males, and there were 12 (2%) cases with dysplasia in the retromolar area. There was no statistically significant difference.

Diagnostic accuracy

The present study determined the diagnostic accuracy of the clinical diagnosis with the dysplastic characteristics. Based on the present study also considered a cut-off range of 55% to 100% based on other literature reporters falling in the range was considered important for diagnosing dysplasia.

A comparative dysplasia evaluation with the clinical diagnosis was performed and represented [Table 3]. A statistically significant relationship between the risk estimates for the clinical diagnosis and dysplasia was noted for all the lesion types. Clinical diagnosis and risk estimates was compared which showed highly significant results for Verucous leukoplakia followed by speckled leukoplakia, where as in case of homogenous and nodular leukoplakia the results were significant [Table 4]. ComA comparison of the Dysplasia with the Clinical categories is presented in [Table 5]. Risk estimates for the clinical presentation and Dysplasia have been mentioned in [Table 6]. The inference could be made that mixed red and white with growth was the most presented clinical category to histo-pathologically represent dysplasia.

Table 3: Comparison of the dysplasia with the clinical diagnosis

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Table 4: Risk estimates for the clinical diagnosis and dysplasia

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Table 5: Comparison of dysplasia with the clinical categories

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Table 6: Risk estimates for the clinical presentation and dysplasia

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Discussion

The present study was conducted to validate clinical presentations of a commonly occurring Leukoplakia lesion and its probability of dysplastic changes over some time. Sivakumar TT et al.,^[17] have reported oral Leukoplakia as the most common potentially malignant lesion (37.1%). Naga SD et al.^[18] have reported that only 12.23% of the OPMLs were referred for biopsies compared to 29.15% of the clinically diagnosed malignant cases. A cover article by ADA has stated Leukoplakia as the commonest OPML, and certain clinically reprehensive erythroplakia histologically reported Oral sub mucous fibrosis.^[19] They have reported that not all Leukoplakia lesions present with dysplastic histo-pathological findings even when comparisons are made over a perisome time rationalizes the need for the present study, where effort has been made to predict the dysplastic changes of a lesion based on their clinical presentation.

Warnakulasuriya S^[20] has reported buccal mucosa as a common site for Leukoplakia lesions. In a study conducted by Jaber MA et al.,^[21] it was found that 6.1% of the retromolar area was reported to have dysplastic changes. In contrast to our study findings, Mehrotra R et al.,^[22] have reported o cases of Leukoplakia in the retromolar area. The higher prevalence of the lesion could be attributed to the increased prevalence of smoking and smokeless tobacco consumption habits among males compared to females.

Mehrotra R et al.,^[22] this study has reported that Leukoplakia is commonest among the age group of 50 to 59 years. Ray JG et al.,^[23] have also reported a higher prevalence among the age group 50 to 69. Longitudinal studies have highlighted that long-standing lesions reported dysplastic changes more than just-formed lesions. This could justify the increased prevalence rate of dysplastic changes among middle-aged individuals compared to younger individuals.

Unlike our study report, most authors reported that homogeneous Leukoplakia had a minimal malignant transformation. Parlatescu I et al.,^[24] have reported that 16% of the non-dysplastic histopathological presentations transform into carcinoma.

The strength of the study includes being one of its kind towards comparing individual clinical presentations and clinical diagnosis correlations with the histopathological dysplastic findings. The weakness of the study, due to the retrospective designs, is that it does not take into account the benefit of surgical intervention of oral epithelial dysplasia in preventing recurrences and malignant development. This study does not include comparisons made with the existing tobacco smoking or chewing habits of the individuals.

A more detailed multi-centric study comparing the patients' habits and the clinical and histopathological correlations is recommended. Concurrently, the results from the current study may also serve as a setting for establishing randomly controlled clinical trials.

Conclusion

The study derives an inference that the clinical presentation of a lesion can predict the underlying dysplastic changes. This study highlights that mixed red and white lesions with growth possess the highest risk of malignant transformations compared to other clinical presentations. Therefore, this necessitates the added responsibility of the screening clinicians who are supposed to carefully refer the patients for histopathological investigations each time he or she encompasses an OPML.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1.	Hsue SS, Wang WC, Chen CH, Lin CC, Chen YK, Lin LM. Malignant transformation in 1458 patients with potentially malignant oral mucosal disorders: A follow-up study based in a Taiwanese hospital. J Oral Pathol Med 2007;36:25-9.
2.	Warnakulasuriya S, Johnson NW, Van der Waal I. Nomenclature and classification of potentially malignant disorders of the oral mucosa. J Oral Pathol Med 2007;36:575-80.
3.	Napier SS, Speight PM. Natural history of potentially malignant oral lesions and conditions: An overview of the literature. J Oral Pathol Med 2008;37:1-10.
4.	Bouquot JE, Weiland LH, Kurland LT. Leukoplakia and carcinoma in situ synchronously associated with invasive oral/oropharyngeal carcinoma in Rochester. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1988;65:199-207.
5.	Kramer IR, El-Labban N, Lee KW. The clinical features and risk of malignant transformation in sublingual keratosis. Br Dent J 1978;144:171-80.
6.	Schepman K, Van der Meij EH, Smeele L, Van der Waal I. Concomitant leukoplakia in patients with oral squamous cell carcinoma. Oral Dis 1999;5:206-9.
7.	Kramer IR, Lucas RB, Pindborg JJ, Sobin LH. Definition of leukoplakia and related lesions: An aid to studies on oral precancer. Oral Surg Oral Med Oral Pathol 1978;46:518-39.
8.	Silverman S Jr, editor. Oral Cancer. 3^rd ed. Atlanta, GA: American Cancer Society; 1990.
9.	Gupta PC, Bhonsle RB, Murti PR, Daftary DK, Mehta FS, Pindborg JJ. An epidemiologic assessment of cancer risk in oral precancerous lesions in India with special reference to nodular leukoplakia. Cancer 1989;63:2247-52.
10.	Silverman S, Gorsky M, Lozada F. Oral leukoplakia and malignant transformation. A follow-up study of 257 patients. Cancer1984;53:563-8.
11.	Neville B, Damm D, Allen C, Bouquot J. Oral and Maxillofacial Pathology. 2^nd ed. Philadelphia: W.B. Saunders; 2002.
12.	Bouquot J, Kurland L, Weiland L. Leukoplakia of the head and neck: Characteristics of 568 lesions with 6,720 person-years of follow-up. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1999;88:202.
13.	Warnakulasuriya S. Histological grading of oral epithelial dysplasia: Revisited. J Pathol 2001;194:294-7.
14.	Bossuyt PM, Reitsma JB, Bruns DE, Gatsonis CA, Glasziou PP, Irwig L, et al. STARD 2015: An updated list of essential items for reporting diagnostic accuracy studies. Radiology 2015;277:826-32.
15.	Axell T, Holmstrup P, Kramer IRH, Pindborg JJ, Shear M, editors. International seminar on oral leukoplakia and associated lesions related to tobacco habits. Community Dent Oral Epidemiol 1984;12:145-54.
16.	World Health Organization Classification of Tumours. Pathology & genetics. Head and neck tumors. International Agency for Research on Cancer (IARC). In: L Barnes, JW Eveson, P Reichart, D Sidransky, editors. Head and Neck Tumors. Lyon: IARC Press; 2005. p. 177-80.
17.	Sivakumar TT, Sam N, Joseph AP. Prevalence of oral potentially malignant disorders and oral malignant lesions: A population-based study in a municipal town of southern Kerala. J Oral Maxillofac Pathol 2018;22:413-4. [PUBMED] [Full text]
18.	Naga SD, Gundamaraju KK, Bujunuru SR, Navakoti P, Kantheti LC, Poosarla C. Prevalence of oral potentially malignant and malignant lesions at a tertiary level hospital in Hyderabad, India. J NTR Univ Health Sci 2014;3(Suppl S1):13-6.
19.	Lingen MW, Abt E, Agrawal N, Chaturvedi AK, Cohen E, D'Souza G, et al. Evidence-based clinical practice guideline for evaluating potentially malignant disorders in the oral cavity: A report of the American Dental Association. J Am Dent Assoc 2017;148:712-7.
20.	Warnakulasuriya S. Oral potentially malignant disorders: A comprehensive review on clinical aspects and management. Oral Oncol 2020;102:104550. doi: 10.1016/j.oraloncology. 2019.104550.
21.	Jaber MA, Porter SR, Speight P, Eveson JW, Scully C. Oral epithelial dysplasia: Clinical characteristics of western European residents. Oral Oncol 2003;39:589-96.
22.	Mehrotra R, Pandya S, Chaudhary AK, Kumar M, Singh M. Prevalence of oral pre-malignant and malignant lesions at a tertiary level hospital in Allahabad, India. Asian Pac J Cancer Prev 2008;9:263-5.
23.	Ray JG, Ganguly M, Rao BS, Mukherjee S, Mahato B, Chaudhuri K. Clinico-epidemiological profile of oral potentially malignant and malignant conditions among areca nut, tobacco and alcohol users in Eastern India: A hospital-based study. J Oral Maxillofac Pathol 2013;17:45-50. [PUBMED] [Full text]
24.	Parlatescu I, Gheorghe C, Coculescu E, Tovaru S. Oral leukoplakia - An update. Maedica (Bucur) 2014;9:88-93.