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Short communication

Licensee OA Publishing London 2013. Creative Commons Attribution License (CC-BY)

For citation purposes: Gomes CC, Gomez RS. Oral leukoplakia: What is achieved by surgical treatment? Annals of Oral & Maxillofacial Surgery 2013 Feb 01;1(1):9.

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Oral leukoplakia: What is achieved by surgical treatment?CC Gomes1, RS Gomez2*

AbstractIntroductionMolecular changes in oral leukoplakia (OL) or in adjacent ‘clinically normal mucosa’ might influence the persi-stence/recurrence of OL, allowing an opportunity for transformation into squamous cell carcinoma. This paper discusses the surgical management of patients with OL.Short communicationClinicians must understand that available treatment options are limited in their capacity to preve-nt oral cancer. Surgical resection is still currently the best technique for management of OL. Patients with OL also need to adjust their lifestyle. ConclusionWe call for further studies to improve our understanding.

IntroductionAccording to a workshop coordinat-ed by the WHO Collaborating Centre for Oral Cancer and Precancer, the term oral leukoplakia (OL) applies to ‘white plaques of questionable risk, having excluded (other) known diseases or disorders that carry no increased risk for cancer’1. OL typi-cally presents as a white lesion of oral mucosa and is diagnosed when all other possible causes of white oral lesions are excluded1. A provi-sional diagnosis is made only when clinical examination is performed and any other clinical diagnosis is

excluded1,2. Histological examination should support the diagnosis being mandatory for histological grading of epithelial dysplasia3. The extent or grade of dysplasia is currently the accepted reference method by which the malignant potential of OL is gauged to predict OL malignant transformation3. Key dysplastic fea-tures of stratified squamous epithe-lium include cellular atypia and loss of stratification4,5. Generally, dyspla-sia is classified by degree as mild, moderate or severe1,4,6.

Despite being the gold stand-ard method to predict malignant potential, there is little agreement between pathologists regarding epi-thelial dysplasia grading, and even nondysplastic lesions may trans-form. Subjectivity in the grading of OL, arbitrarily set grading thresh-olds, lack of calibration and limited knowledge of which criteria best predict malignant transformation may explain these disparities4,7,8. However, a meta-analysis has shown that the grade of dysplasia in OL and eventual malignant transformation correlate significantly9. Although ex-cision may not eliminate this trans-formation, the likelihood is at least reduced9.

Homogeneous OL lesions are flat, thin, uniformly white in colour and carry a low risk of malignant transfor-mation1,2,10. On the other hand, mixed white and red lesions, with irregu-larly flat, nodular or verrucous ar-eas, qualify as nonhomogeneous, and these are at high risk of progression to cancer2. The term oral verrucous leukoplakia signifies lesions with multifocal presentation that are re-sistant to treatment and are at a high risk of emergent cancer2. The prima-ry risk factors for malignant transfor-mation of OL are: (i) female gender,

(ii) lesion chronicity, (iii) nonsmoker status, (iv) heterogeneous features, (v) tongue and floor of mouth sites, (vi) size >200 mm2, (vii) severity of dysplasia, (viii) aneuploidy and (xi) loss of heterozygosity2,11. Some molecular markers have shown promise in predicting the progres-sion of premalignant oral lesions to squamous cell carcinoma, but none as yet are in routine clinical use12.

Surgical techniques for manag-ing patients with OL vary. However, randomized clinical trials have not addressed their efficacies in terms of preventing recurrent OL or its ma-lignant transformation. This paper assesses the surgical treatment and what is achieved of patients with OL.

Short Communication Treatment of OLAt present, there is no scientific evi-dence that any manner of interven-tion prevents the development of squamous cell carcinoma in OL10. Recurrences may arise after surgi-cal resection, based on mucosal field changes, which explains why wide-spread lesions pose a substantial threat of persistence/recurrence or malignant transformation. By definition, the concept of field can-cerization denotes the presence of microscopic epithelial changes sur-rounding an oral cancer. Now we realize that even clinically normal mucosa, devoid of dysplasia at a mi-croscopic level, might harbour mo-lecular alterations predisposed to malignant transformation. Surgical excision is therefore ineffective in eradicating OL or preventing even-tual malignancy. Instead, it is widely used for its potential as a diagnostic tool13. Of course, this benefit may be curtailed, if incisional biopsy is done rather than complete excision.

* Corresponding authorEmail: rsgomez@ufmg.br1 Department of Pathology, Biological Sciences

Institute, School of Dentistry, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais – Brazil

2 Department of Oral Pathology, School of Dentistry, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais – Brazil

Page 2 of 3

Short communication

Licensee OA Publishing London 2013. Creative Commons Attribution License (CC-BY)

For citation purposes: Gomes CC, Gomez RS. Oral leukoplakia: What is achieved by surgical treatment? Annals of Oral & Maxillofacial Surgery 2013 Feb 01;1(1):9.

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indicated treatments. Future studies may help illuminate the clinical relevance of any distinction in this regard.

ConclusionAny expression of molecular altera-tions in ‘clinically normal mucosa’ at the margins of OL carries an in-creased risk of progression to squa-mous cell carcinoma22. Because the means of assessing surgical margins may not be routinely available, clini-cians must factor this into treatment decisions. In general, all patients with OL should be monitored regularly.

Despite a lack of evidence, surgi-cal resection still remains the best practice for management of OL, re-gardless of histologic grade. Lifestyle modifications (i.e. cessation of smok-ing and alcohol consumption) in patients with OL are also warranted.

AcknowledgementsThis work was supported by a grant from the ConselhoNacional de Desenvolvimento a Pesquisa (CNPq) and the Coordenação de Aperfeiçoamento de Pessoal de Nível

malignant oral lesions, there is no standard approach for prevention of head and neck malignancies21,22. A serious drawback of chemoprevention is the relapse of lesions after discontinuing treatment.

Recurrence Versus Second Primary OLResection is the most common treat-ment modality in OL. However, cli-nicians must bear in mind that mo-lecular alterations may or may not be manifested in ‘clinically normal mucosa’ (Figure 1). When surgical margins are involved, removal of the lesion will not eliminate ‘altered clones’. Thus, any relapse should be considered a persistent/recurrent disease. In the event that the mar-gins do not present molecular al-terations, any new lesion appearing at the same site is better viewed as a second primary OL. Currently, there is no proof that recurrent and sec-ond primary OL differ in respective risks of malignant transformation or

Development of a squamous cell carcinoma is not at all unusual in a white plaque displaying no earlier clinical signs of malignancy. In short, excisional biopsy of OL does not prevent malignant transformation (primary prevention), but it does promote early diagnosis of cancer (secondary prevention) and is indi-cated for every lesion13.

In one retrospective study of OL, the incidence of oral squamous cell carcinoma was determined in patients treated surgically and/or medically and in those managed only by regular clinical follow-ups14. Given that the two groups did not differ significantly, one may argue that OL lesions destined for malig-nant transformation will suffer such fate regardless of active interven-tion. However, a bias related to group heterogeneity cannot be excluded, because the patients were not ran-domly assigned.

CO2 laser resection is the most commonly used laser method for treat-ment of OL15. The rate of recurrence after CO2 laser resection varies from 7.7% to 66%, with malignant trans-formation occurring in 7.7–14.2%15–19. Continuous smoking after surgical removal and widespread lesions are prognostic indicators for recurrence after laser surgery15. The haemostasis achieved by laser ablation is clearly advantageous as well as the ability to preserve surrounding tissue and the positive wound healing attached. Un-fortunately, no tissue is available for histopathological examination7.

Photodynamic therapy has also been used to manage patients with OL and oral erythroplakia. In pa-tients with OL, results have proved unsatisfactory, but a high success rate (66–95%) has been reported with erythroplakia. The less keratinized surface and more decisive dysplasia of the latter perhaps facilitate greater penetration by photosensitizer20.

Despite extensive investigations and a number of advances in systemic therapy for patients with potentially

Figure 1: Oral leukoplakia (lateral border of tongue). Clinically normal mucosa at margins may in fact harbour molecular alterations, contributing to the persistence/recurrence of subsequent squamous cell carcinoma.

Discussion

Page 3 of 3

Short communication

Licensee OA Publishing London 2013. Creative Commons Attribution License (CC-BY)

For citation purposes: Gomes CC, Gomez RS. Oral leukoplakia: What is achieved by surgical treatment? Annals of Oral & Maxillofacial Surgery 2013 Feb 01;1(1):9.

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15. Yang SW, Tsai CN, Lee YS, ChenTA. Treatment outcome of dysplastic oral leukoplakia with carbon dioxide laser--emphasis on the factors affecting recurrence. J Oral Maxillofac Surg. 2011 Jun;69(6):e78–87.16. Ishii J, Fujita K, Komori T. Laser sur-gery as a treatment for oral leukoplakia. Oral Oncol. 2003 Dec;39(8):759–69.17. Hamadah O, Thomson PJ. Factors af-fecting carbon dioxide laser treatment for oral precancer: a patient cohort study. Lasers Surg Med. 2009 Jan;41(1):17–25.18. Lim B, Smith A, Chandu A. Treatmentof oral leukoplakia with carbon dioxide and potassium-titanyl-phosphate lasers: a comparison. J Oral Maxillofac Surg. 2010 Mar;68(3):597–601.19. Brouns E, Baart J, Karagozoglu K,Aartman I, Bloemena E, van der Waal I. Treatment results of CO(2) laser vapori-sation in a cohort of 35 patients with oral leukoplakia. Oral Dis. 2012 Sep.20. Swain N, Kumar SV, Rautray S, Richa.Reappraisal of photodynamic therapy as first-line therapy in management of oral pre-malignant lesions. Oral Oncol. 2012 Oct;48(10):915–6.21. William WN, Jr. Oral premalignant le-sions: any progress with systemic thera-pies? Curr Opin Oncol. 2012 May;24(3): 205–10.22. Giaretti W, Maffei M, Pentenero M,Scaruffi P, Donadini A, Di Nallo E, et al. Genomic aberrations in normal appear-ing mucosa fields distal from oral poten-tially malignant lesions. Cell Oncol. 2012 Feb;35(1):43–52.

How should we manage oral leukoplakia? Br J Oral Maxillofac Surg. 2012 Nov.8. Fleskens S, Slootweg P. Grading sys-tems in head and neck dysplasia: their prognostic value, weaknesses and utility. Head Neck Oncol. 2009 May;1:11.9. Mehanna HM, Rattay T, Smith J, McConkey CC. Treatment and follow-up of oral dysplasia – a systematic review and meta-analysis. Head Neck. 2009 Dec; 31(12):1600–9.10. van der Waal I. Potentially malig-nant disorders of the oral and oro-pharyngeal mucosa; present concepts of management. Oral Oncol. 2010 Jun; 46(6):423–5.11. Zhang L, Poh CF, Williams M, LarondeDM, Berean K, Gardner PJ, et al. Loss of heterozygosity (LOH) profiles-- validated risk predictors for progression to oral cancer. Cancer Prev Res. 2012 Sep;5(9): 1081–9.12. Pitiyage G, Tilakaratne WM, TavassoliM, Warnakulasuriya S. Molecular mark-ers in oral epithelial dysplasia: review. J Oral Pathol Med. 2009 Nov;38(10): 737–52.13. Lodi G, Porter S. Management of po-tentially malignant disorders: evidence and critique. J Oral Pathol Med. 2008 Feb; 37(2):63–9.14. Schepman KP, van der Meij EH,Smeele LE, van der Waal I. Malignant transformation of oral leukoplakia: a fol-low-up study of a hospital-based popula-tion of 166 patients with oral leukoplakia from The Netherlands. Oral Oncol. 1998 Jul;34(4):270–5.

Superior (CAPES), MS/SCTIE/Decit, Brazil. Professors RS Gomez and CC Gomes are research fellows at CNPq.

Abbreviations listOL, oral leukoplakia

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