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LETTER TO THE EDITOR
Year : 2019  |  Volume : 56  |  Issue : 4  |  Page : 375-378
 

The impact of clinicopathological aspects on the recurrence of oral leukoplakia: A retrospective study in a cohort of 83 patients from the north of Spain


1 Oral Medicine, Oral Surgery and Implantology Unit, Faculty of Medicine and Odontology, University of Santiago de Compostela, Santiago de Compostela, Spain
2 GI-1319 Research Group, Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain
3 Oral Medicine and Pathology, Department of Stomatology II, University of the Basque Country (UPV/EHU), Leioa, Spain
4 Oral Medicine, Oral Surgery and Implantology Unit, Faculty of Medicine and Odontology, University of Santiago de Compostela; GI-1319 Research Group, Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain

Date of Web Publication11-Oct-2019

Correspondence Address:
Sergio Pineiro-Donis
Oral Medicine, Oral Surgery and Implantology Unit, Faculty of Medicine and Odontology, University of Santiago de Compostela, Santiago de Compostela
Spain
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijc.IJC_230_18

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How to cite this article:
Pineiro-Donis S, Torres-López M, García-García A, Marichalar-Mendía X, Gándara-Vila P, Lorenzo-Pouso AI, Blanco-Carrión A, Pérez-Sáyans M. The impact of clinicopathological aspects on the recurrence of oral leukoplakia: A retrospective study in a cohort of 83 patients from the north of Spain. Indian J Cancer 2019;56:375-8

How to cite this URL:
Pineiro-Donis S, Torres-López M, García-García A, Marichalar-Mendía X, Gándara-Vila P, Lorenzo-Pouso AI, Blanco-Carrión A, Pérez-Sáyans M. The impact of clinicopathological aspects on the recurrence of oral leukoplakia: A retrospective study in a cohort of 83 patients from the north of Spain. Indian J Cancer [serial online] 2019 [cited 2019 Nov 18];56:375-8. Available from: http://www.indianjcancer.com/text.asp?2019/56/4/375/268955




At the last meeting of the WHO, which was held in 2005, leukoplakia was defined as: A white plaque of questionable risk having excluded (other) known diseases or disorders that carry no increased risk for cancer.[1] It is estimated that the overall prevalence in Spain is 1.72%–2.60%, nonetheless this range varies considerably depending on the region of the country, the usual toxic habits, factors that condition the response to the treatment, and the risk of recurrence.[1],[2]

There are several surgical modalities for treating oral leukoplakia (OL): cold scalpel excision, cryosurgery, laser excision or laser vaporization, and photodynamic therapy. However, the results of these techniques have not been proven.[2] The different treatment modalities reported a wide range of OL recurrence rates, from 2% to 40%, and an annual recurrence rate from 5% to 10%.[3],[4],[5],[6],[7]

The aim of this study was to evaluate the time of recurrence of leukoplakic lesions, taking into consideration the degree of dysplasia and the clinical category in order to determine which leukoplakia profile is more prone to recurrence.

This was a retrospective observational study that has been conducted according to the recommendations of the STROBE guidelines. We selected a cohort of patients who had been clinically diagnosed with OL and who had confirmed histopathology. Their lesions were treated using CO2 until they had been completely eliminated, without recurrence within a period of more than six months. We selected all patients with lesions who had been treated at the Oral Medicine Unit and who met the inclusion criteria.

The sample consisted of 83 patients with OL lesions. For the sample and power calculation, we used the proportion/one-sided method; for a sample of 80 patients, with a 50% chance of recurrence, and an error rate of 10%, the statistical power is almost 70%. The clinical variables analyzed included age, sex, degree of dysplasia (according to the WHO 2005 classification), smoking (smoker, nonsmoker, ex-smoker), clinical appearance of leukoplakia [Figure 1] (homogeneous, nodular, mottled-erythroplastic or verrucous), number of lesions (single or multiple), location of the lesion, size (<2 cm, 2–4 cm and >4 cm), clinical follow-up (change/consistency in the initial clinical classification), type of biopsy (incisional or excisional), location of the biopsy, malignant transformation, and recurrence. This study was approved by the ethical committee of Galicia (Ref. 2016/337).
Figure 1: Clinical forms of OL. a) Homogeneous. b) Verrucous. c) Nodular. d) Speckled-erythroleukoplakia

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The inclusion and exclusion criteria are outlined below.

Inclusion: We included patients who had had verrucous leukoplakia lesions at some point that had subsequently been confirmed by means of a biopsy. For lesions with a variety of presentations over several follow-ups (sometimes the lesions change the clinical presentation), we considered the most frequent clinical presentation from all of the control appointments.

Exclusion: We excluded subjects with the following characteristics: patients without an initial histological diagnosis, patients with a follow-up period of less than six months, patients with the clinical presentation or histological findings of white or predominantly white benign disease, patients without a clinical image of the lesion under study, and patients without any anatomopathological material that would allow us to confirm the initial diagnosis.

[Table 1] presents a summary of the clinical characteristics of the study sample.
Table 1: Clinical and pathological characteristics of patients

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All of the patients included in this study underwent a biopsy following a routine procedure. When the lesions were of a reasonable surgical size, they were biopsied by complete excision; this was also used as a therapeutic method. Any lesions of more than 4 cm, located in areas which were compromised by vascular or nervous structures, or which were difficult to access, were biopsied by incisional technique and were later treated using CO2 laser vaporization.

Chi-square and ANOVA tests were used for the bivariate analysis. In order to verify the relative risk of the different covariables on recurrence, a multivariate logistic regression analysis was carried out. The mean time of recurrence was calculated using the Kaplan–Meier curves.

The results of our study were obtained from a population of 83 patients with a mean age of 66.5 years, standard deviation (SD) of 8.92, aged between 46 and 86 years. The maximum follow-up of the patients was 142.43 months with a mean of 42.17 months (SD = 45.40). The patients' clinical and pathological characteristics are shown in [Table 1].

A statistical relationship was obtained between the mean recurrence time and the clinical forms, comparing all clinical forms of leukoplakia (nodular, speckled-erythroleukoplakia, homogeneous, and verrucous). Recurrence in the nodular form appears at 12.05 months on average (CI 6.81-17.29), followed by the homogeneous form at 32.08 months (CI 15.33-48.83), verrucous at 52.57 months (CI 38.01–67.14), and speckled-erythroleukoplakia at 79.01 months (CI 0.00-164.24) (log rank 16.596; P = 0.001). When comparing verrucous leukoplakia with the remaining forms of leukoplakia, statistically significant differences were observed between the average time of recurrence and the clinical forms. The average recurrence time for verrucous leukoplakia was 52.7 months (CI 38.1–67.1), whereas the average recurrence time for the other forms of leukoplakia was 25.6 months (CI 14.7–36. 6) (log rank 7.827; P = 0.005) [Figure 2].
Figure 2: Kaplan–Meier curve for recurrence according to the clinical forms of OL

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Statistically significant differences were observed between the mean time of recurrence and the degree of dysplasia. The average recurrence time for patients without dysplasia was 35.33 months (CI 23.43–47.23). The mean recurrence of patients with dysplasia was 56.7 months (CI 37.8–75.5, P = 0.048), and the overall mean recurrence time was 42.17 months (CI 31.9–52.44) (log rank 3.897, P = 0.048) [Figure 3].
Figure 3: Kaplan–Meier curve for recurrence according to the presence of dysplasia

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The recurrence rate in our study was 91.6%, and 15% of lesions exhibited clinical changes. Several studies have demonstrated that 7.7%–45% of lesions recur after surgical treatment.[4],[5],[6],[7],[8],[9] Kuribayashi et al.[8] found that the recurrence rate following curative surgical resection was 15.1%, with the most common site being the gingiva. Recurrence was more likely in cases with positive margins. No significant association was observed between recurrence and the degree of epithelial dysplasia. Chandu et al.[9] observed a disease-free survival of 55.4% at 3 years among their cohort of patients (recurrence rate of 45%), in particular, in patients who did not give up toxic habits. In our series, almost 65% of the lesions were verrucous, with an intrinsic risk of recurrence, proliferative behavior, and even malignancy. There was a considerable follow-up period (almost 12 years in some patients), which explains the high recurrence of this pathology in our cohort and its carcinogenic potential.

With regard to the association between the average time of recurrence and the degree of dysplasia [Figure 3], the recurrence phenomenon is more frequent in patients without dysplasia than in patients with dysplasia (similar to as Kuribayashi and Cols.).[7] After 20 months of follow-up, more than 60% of the patients without dysplasia had already experienced recurrence. On the other hand, less than 30% of patients with dysplasia had experienced recurrence. Diajil et al.[9] described lesions with a high degree of dysplasia, which present a 62% disease-free survival rate after 10 years of follow-up.

Dysplasia in the oral premalignant lesions confers the capacity to stimulate the growth and division of the cells contained in basal layers of the epithelium; therefore, this type of lesion should be more susceptible to recurrence and should be refractory to surgical treatment. However, this fact has not been demonstrated.[10] Jerjes et al. evaluated the association between recurrence and the degree of dysplasia by means of a bivariate analysis, finding moderate-severe levels of dysplasia in the recurrence of leukoplakia.[11] On the other hand, Chainani-Wu et al. did not find any significant differences in their logistic regression analysis that was performed in order to evaluate the histopathology of the lesion and its recurrence.[12]

When comparing the mean recurrence time and the clinical forms [Figure 2], recurrence occurs less frequently in the verrucous form than in the clinical forms of leukoplakia. After 10 months of follow-up, approximately 60% of patients without verrucous leukoplakia had experienced at least one episode of recurrence. In the same period of time, less than 30% of patients with homogeneous leukoplakia had experienced recurrence. A previous study evaluated the risk of recurrence according to the clinical form of the lesions, determining that nonhomogeneous lesions present the greatest risk.[5]

With regards to the mean recurrence time among all of the clinical forms (nodular, speckled-erythroleukoplakia, homogeneous, and verrucous), the recurrence of nodular leukoplakia is more frequent and occurs more prematurely in comparison with the other clinical forms. Before reaching the 20-month follow-up, more than 70% of patients with the nodular form had already experienced recurrence at least once. In contrast, only 45% and 30% of patients with the homogeneous and verrucous forms, respectively, had experienced recurrence. In this period, recurrence was not recorded for the speckled-erythroleukoplakia form, probably due to a less conservative surgical excision.[13]

There are different treatment modalities for leukoplakia lesions; however, the literature does not offer a definitive therapeutic guide. In a recent article, Monteiro et al. evaluated the impact of different types of laser on leukoplakia lesions in terms of their recurrence. They concluded that the Er: YAG laser is a promising option for treating OL.[14]

The limitations of our study include the controversy surrounding dysplasia and its gradation, the degree of coherence among various pathologists over numerous years, the changing forms of the lesions, and the effect of consuming mutagenic agents on the degree of dysplasia during the follow-up period. As we can confirm in this study, the recurrence of OL and the clinical changes to forms that are more susceptible to recurrence is high, even when the treatment has been performed by a specialist in oral medicine. This generates the need for the follow-up periods for these patients to be reduced, sometimes even monthly.

After having analyzed our results and compared them with the results obtained in other studies, we are able to conclude that recurrence of leukoplakia remains uncertain. The role of the clinical form and especially dysplasia is not entirely clear, not only in terms of the recurrence rate but also in terms of the time of recurrence. The warty forms tend to grow in a proliferative way and it is possible that this leads to the excision treatment being performed by the clinicians in a broader (less conservative) way. For this reason, and in the absence of consensus and/or clinical protocols and given its recurrence, we must consider leukoplakia as a high-risk lesion, and we must specifically identify the surgical margins and expand where possible said safety margins for the surgical excision and/or the vaporization.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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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.  Back to cited text no. 1
    
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Lodi G, Porter S. Management of potentially malignant disorders: Evidence and critique. J Oral Pathol Med 2008;37:63-9.  Back to cited text no. 2
    
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van der Waal I. Oral potentially malignant disorders: Is malignant transformation predictable and preventable? Med Oral Patol Oral Cir Bucal 2014;19:e386-90.  Back to cited text no. 3
    
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Mogedas-Vegara A, Hueto-Madrid J, Chimenos-Küstner E, Bescós-Atín C. The treatment of oral leukoplakia with the CO2 laser: A retrospective study of 65 patients. J Craniomaxillofac Surg 2015;43:677-81.  Back to cited text no. 4
    
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Yang S, Tsai C, Lee Y, Chen T. Treatment outcome of dysplastic oral leukoplakia with carbon dioxide laser-emphasis on the factors affecting recurrence. J Oral Maxillofac Surg 2011;69:e78-87.  Back to cited text no. 5
    
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Saito T, Sugiura C, Hirai A, Notani K, Totsuka Y, Shindoh M, et al. Development of squamous cell carcinoma from pre-existent oral leukoplakia: With respect to treatment modality. Int J Oral Maxillofac Surg 2001;30:49-53.  Back to cited text no. 6
    
7.
Kuribayashi Y, Tsushima F, Sato M, Morita K, Omura K. Recurrence patterns of oral leukoplakia after curative surgical resection: Important factors that predict the risk of recurrence and malignancy. J Oral Pathol Med 2012;41:682-8.  Back to cited text no. 7
    
8.
Chandu A, Smith AC. The use of CO 2 laser in the treatment of oral white patches: Outcomes and factors affecting recurrence. Int J Oral Maxillofac Surg2005;34:396-400.  Back to cited text no. 8
    
9.
Diajil A, Robinson CM, Sloan P, Thomson PJ. Clinical outcome following oral potentially malignant disorder treatment: A 100 patient cohort study. Int J Dent 2013;2013:8. Article ID 809248.  Back to cited text no. 9
    
10.
Gándara-Vila P, Perez-Sayans M, Suarez-Penaranda JM, Gallas-Torreira M, Somoza-Martin J, Reboiras-Lopez MD, et al. Survival study of leukoplakia malignant transformation in a region of northern Spain. Med Oral Patol Oral Cir Bucal 2018;23:e413-20.  Back to cited text no. 10
    
11.
Jerjes W, Upile T, Hamdoon Z, Al-Khawalde M, Morcos M, Mosse CA, et al. CO2 laser of oral dysplasia: Clinicopathological features of recurrence and malignant transformation. Lasers Med Sci 2012;27:169-79.  Back to cited text no. 11
    
12.
Chainani-Wu N, Lee D, Madden E, Sim C, Collins K, Silverman S Jr. Clinical predictors of oral leukoplakia recurrence following CO2 laser vaporization. J Craniomaxillofac Surg 2015;43:1875-9.  Back to cited text no. 12
    
13.
Yang SW, Tsai CN, Lee YS, Chen TA: Postoperative recurrence is the associated factor of malignant change of dysplastic oral leukoplakia. ORL J OtorhinolaryngolRelat Spec 2010;72:280-90.  Back to cited text no. 13
    
14.
Monteiro L, Barbieri C, Warnakulasuriya S, Martins M, Salazar F, Pacheco JJ, et al. Type of surgical treatment and recurrence of oral leukoplakia: A retrospective clinical study. Med Oral Patol Oral Cir Bucal 2017;22:e520-26.  Back to cited text no. 14
    


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