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.

Short communication

Oral Surgery & Medicine

Oral leukoplakia: What is achieved by surgical treatment?

CC Gomes1, RS Gomez2*

Authors affiliations

(1) 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.

* Corresponding author Email:



Molecular changes in oral leukoplakia (OL) or in adjacent ‘clinically normal mucosa’ might influence the persistence/recurrence of OL, allowing an opportunity for transformation into squamous cell carcinoma.

Short communication

Clinicians must understand that available treatment options are limited in their capacity to prevent oral cancer.

Surgical resection is still currently the best technique for management of OL. Patients with OL also need to adjust their lifestyle.


We call for further studies to improve our understanding.


According to a workshop coordinated 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 typically presents as a white lesion of oral mucosa and is diagnosed when all other possible causes of white oral lesions are excluded[1]. A provisional diagnosis is made only when clinical examination is performed and any other clinical diagnosis is excluded[1,2]. Histological examination should support the diagnosis being mandatory for histological grading of epithelial dysplasia[3]. 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 transformation[3]. Key dysplastic features of stratified squamous epithelium include cellular atypia and loss of stratification[4,5]. Generally, dysplasia is classified by degree as mild, moderate or severe[1,4,6].

Despite being the gold standard method to predict malignant potential, there is little agreement between pathologists regarding epithelial dysplasia grading, and even nondysplastic lesions may transform. Subjectivity in the grading of OL, arbitrarily set grading thresholds, lack of calibration and limited knowledge of which criteria best predict malignant transformation may explain these disparities[4,7,8]. However, a meta-analysis has shown that the grade of dysplasia in OL and eventual malignant transformation correlate significantly[9]. Although excision may not eliminate this transformation, the likelihood is at least reduced[9].

Homogeneous OL lesions are flat, thin, uniformly white in colour and carry a low risk of malignant transformation[1,2,10]. On the other hand, mixed white and red lesions, with irregularly flat, nodular or verrucous areas, qualify as nonhomogeneous, and these are at high risk of progression to cancer[2]. The term oral verrucous leukoplakia signifies lesions with multifocal presentation that are resistant to treatment and are at a high risk of emergent cancer[2]. The primary risk factors for malignant transformation 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 heterozygosity[2,11]. Some molecular markers have shown promise in predicting the progression of premalignant oral lesions to squamous cell carcinoma, but none as yet are in routine clinical use[12].

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

Short Communication

Treatment of OL

At present, there is no scientific evidence that any manner of intervention prevents the development of squamous cell carcinoma in OL[10]. Recurrences may arise after surgical resection, based on mucosal field changes, which explains why widespread lesions pose a substantial threat of persistence/recurrence or malignant transformation. By definition, the concept of field cancerization denotes the presence of microscopic epithelial changes surrounding an oral cancer. Now we realize that even clinically normal mucosa, devoid of dysplasia at a microscopic level, might harbour molecular alterations predisposed to malignant transformation. Surgical excision is therefore ineffective in eradicating OL or preventing eventual malignancy. Instead, it is widely used for its potential as a diagnostic tool[13]. Of course, this benefit may be curtailed, if incisional biopsy is done rather than complete excision. 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 indicated for every lesion[13].

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-ups[14]. Given that the two groups did not differ significantly, one may argue that OL lesions destined for malignant transformation will suffer such fate regardless of active intervention. However, a bias related to group heterogeneity cannot be excluded, because the patients were not randomly assigned.

CO2 laser resection is the most commonly used laser method for treatment of OL[15]. The rate of recurrence after CO2 laser resection varies from 7.7% to 66%, with malignant transformation occurring in 7.7–14.2%[15,16,17,18,19]. Continuous smoking after surgical removal and widespread lesions are prognostic indicators for recurrence after laser surgery[15]. The haemostasis achieved by laser ablation is clearly advantageous as well as the ability to preserve surrounding tissue and the positive wound healing attached. Unfortunately, no tissue is available for histopathological examination[7].

Photodynamic therapy has also been used to manage patients with OL and oral erythroplakia. In patients 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 photosensitizer[20].

Despite extensive investigations and a number of advances in systemic therapy for patients with potentially malignant oral lesions, there is no standard approach for prevention of head and neck malignancies[21]. A serious drawback of chemoprevention is the relapse of lesions after discontinuing treatment. In addition, there is no evidence that such therapy reduces the incidence of oral cancer long term.

Recurrence Versus Second Primary OL

Resection is the most common treatment modality in OL. However, clinicians must bear in mind that molecular 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 margins do not present molecular alterations, any new lesion appearing at the same site is better viewed as a second primary OL. Currently, there is no proof that recurrent and second primary OL differ in respective risks of malignant transformation or indicated treatments. Future studies may help illuminate the clinical relevance of any distinction in this regard.

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.


Any expression of molecular alterations in ‘clinically normal mucosa’ at the margins of OL carries an increased risk of progression to squamous cell carcinoma[22]. Because the means of assessing surgical margins may not be routinely available, clinicians must factor this into treatment decisions. In general, all patients with OL should be monitored regularly.

Despite a lack of evidence, surgical resection still remains the best practice for management of OL, regardless of histologic grade. Lifestyle modifications (i.e. cessation of smoking and alcohol consumption) in patients with OL are also warranted.


This work was supported by a grant from the ConselhoNacional de Desenvolvimento a Pesquisa (CNPq) and the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), MS/SCTIE/Decit, Brazil. Professors RS Gomez and CC Gomes are research fellows at CNPq.

Abbreviations list

OL, oral leukoplakia

Authors contribution

All authors contributed to conception and design, manuscript preparation, read and approved the final manuscript.

Competing interests

None declared.

Conflict of interests

None declared.


All authors abide by the Association for Medical Ethics (AME) ethical rules of disclosure.


  • 1. Warnakulasuriya S, Johnson NW, van der Waal I. Nomenclature and classification of potentially malignant disorders of the oral mucosa. J Oral Pathol Med 2007 Nov;36(10):575-80.
  • 2. van der Waal I . Potentially malignant disorders of the oral and oropharyngeal mucosa; terminology, classification and present concepts of management. Oral Oncol 2009 Apr–May;45(4–5):317-23.
  • 3. Tilakaratne WM, Sherriff M, Morgan PR, Odell EW. Grading oral epithelial dysplasia: analysis of individual features. J Oral Pathol Med 2011 Aug;40(7):533-40.
  • 4. Warnakulasuriya S, Reibel J, Bouquot J, Dabelsteen E. Oral epithelial dysplasia classification systems: predictive value, utility, weaknesses and scope for improvement. J Oral Pathol Med 2008 Mar;37(3):127-33.
  • 5. Napier SS, Speight PM. Natural history of potentially malignant oral lesions and conditions: an overview of the literature. J Oral Pathol Med 2008 Jan;37(1):1-10.
  • 6. Speight PM . Update on oral epithelial dysplasia and progression to cancer. Head Neck Pathol 2007 Sep;1(1):61-6.
  • 7. Kumar A, Cascarini L, McCaul JA, Kerawala CJ, Coombes D, Godden D. How should we manage oral leukoplakia? Br J Oral Maxillofac Surg. 2012 Nov.
  • 8. Fleskens S, Slootweg P. Grading systems in head and neck dysplasia: their prognostic value, weaknesses and utility. Head Neck Oncol 2009 May;111.
  • 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 malignant disorders of the oral and oropharyngeal mucosa; present concepts of management. Oral Oncol 2010 Jun;46(6):423-5.
  • 11. Zhang L, Poh CF, Williams M, Laronde DM, Berean K, Gardner PJ. 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, Tavassoli M, Warnakulasuriya S. Molecular markers in oral epithelial dysplasia: review. J Oral Pathol Med 2009 Nov;38(10):737-52.
  • 13. Lodi G, Porter S. Management of potentially 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 follow-up study of a hospital-based population of 166 patients with oral leukoplakia from The Netherlands. Oral Oncol 1998 Jul;34(4):270-5.
  • 15. Yang SW, Tsai CN, Lee YS, Chen TA. 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 surgery as a treatment for oral leukoplakia. Oral Oncol 2003 Dec;39(8):759-69.
  • 17. Hamadah O, Thomson PJ. Factors affecting 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. Treatment of 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 vaporisation 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 lesions: any progress with systemic therapies? Curr Opin Oncol. 2012 May;24(3):205-10.
  • 22. Giaretti W, Maffei M, Pentenero M, Scaruffi P, Donadini A, Di Nallo E. Genomic aberrations in normal appearing mucosa fields distal from oral potentially malignant lesions. Cell Oncol 2012 Feb;35(1):43-52.
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