ORIGINAL ARTICLE Malignant transformation of oral leukoplakia in a well-defined cohort of 144 patients EREA Brouns 1 , JA Baart 1 , KH Karagozoglu 1 , IHA Aartman 2 , E Bloemena 1,3 , I van der Waal 1 1 Department of Oral and Maxillofacial Surgery and Oral Pathology, VU University Medical Center (VUmc)/Academic Centre for Dentistry Amsterdam (ACTA), Amsterdam; 2 Department of Social Dentistry and Behavioural Sciences, Academic Centre for Dentistry Amsterdam (ACTA), Amsterdam; 3 Department of Pathology, VU University Medical Center (VUmc), Amsterdam The Netherlands OBJECTIVES: Oral leukoplakia is a potentially malig- nant disorder of the oral mucosa. The aim of this retro- spective study was to identify the factors that possibly predict malignant transformation in a well-defined cohort of patients with a long-term follow-up. All leuko- plakias were staged according to a clinicopathological classification and staging system. Furthermore, a certainty factor has been used with which the diagnosis has been established. MATERIAL AND METHODS: The group consisted of 144 patients. The size, presence and degree of epithelial dysplasia were incorporated into a clinicopathological classification and staging system. Initial management consisted of surgical excision, CO 2 laser vaporisation or observation only. The mean follow-up period was 51.2 months (s.d. = 39.33, range 12–179 months). RESULTS: In 16 of 144 patients (11%), malignant trans- formation occurred between 20 and 94 months (mean 57.0 months) after the first visit, the annual malignant transformation rate being approximately 2.6%. A large size of the lesion (  4 cm) showed to be the only sta- tistically significant predictor of malignant transforma- tion (P = 0.034). CONCLUSION: A size of  4 cm showed to be the only significant predicting factor of malignant transfor- mation in oral leukoplakia. No other epidemiological, aetiological, clinical or histopathological parameters were of statistical significance. Oral Diseases (2014) 20, e19–e24 Keywords: potentially malignant oral disorder; oral leukoplakia; malignant transformation; oral epithelial dysplasia; oral cancer Introduction Oral leukoplakia is a potentially malignant disorder which means that in this morphologically altered tissue, squa- mous cell carcinoma is more likely to occur than in its apparently normal counterpart (Warnakulasuriya et al, 2007). The reported annual malignant transformation of oral leukoplakia into oral squamous cell carcinoma (OSCC) is approximately 1–2% (van der Waal, 2009). Several factors have been suggested to predict an increased risk of malignant transformation of oral leuko- plakia, such as age, gender, tobacco habits, homogeneity and size of the lesion, oral subsite, degree of epithelial dysplasia, if present, loss of heterozygosity, survivin, matrix metalloproteinase 9 and DNA content (Schepman et al, 1998; Dietrich et al, 2004; Holmstrup et al, 2006; Fillies et al, 2007; Smith et al, 2009; van der Waal, 2009; Bremmer et al, 2011; Brouns et al, 2012b). The possible role of human papilloma virus infection with regard to malignant transformation of oral leukoplakia is yet unclear (Syrjanen et al, 2011; Feller and Lemmer, 2012). Manage- ment of oral leukoplakia consists of surgical excision, laser surgery, CO 2 laser vaporisation and observation (Mehanna et al, 2009; Ribeiro et al, 2010). The aim of the present retrospective study was to iden- tify the factors that possibly predict malignant transforma- tion in a well-defined cohort of patients with a long-term follow-up. All leukoplakias were staged according to a clinicopathological classification and staging system. Fur- thermore, a certainty factor has been used with which the diagnosis has been established. Material and methods Patients For the purpose of this retrospective study, 144 consecu- tive patients were included who were referred to the Department of Oral and Maxillofacial Surgery and Oral Pathology at VU Medical Center/ACTA, Amsterdam, the Netherlands, between 1997 and 2012 and in whom a definitive clinicopathological diagnosis of oral leukoplakia was established. In case of possible aetiological factors, a Correspondence: Prof. Isa€ ac van der Waal, Department of Oral and Maxillofacial Surgery and Oral Pathology, VU University Medical Cen- ter, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands. Tel: +31 20 4444039, Fax: +31 20 4444046, E-mail: i.vanderwaal@vumc.nl Received 28 November 2012; revised 26 February 2013; accepted 26 February 2013 Oral Diseases (2014) 20, e19–e24 doi:10.1111/odi.12095 © 2013 John Wiley & Sons A/S All rights reserved www.wiley.com