Determinants to Progression to Cancer of Oral Premalignant Disorders

To the Editor We read with interest the article by Villa et al1 reporting the rate and determinants of malignant transformation of oral premalignant disorders (OPMDs).1 In line with previous literature, they found a higher risk of transformation to oral cancer for oral erythroplakia (50%) and lower for oral lichen planus (only 1 case out of 468 patients). The most frequent lesion diagnosed was oral leukoplakia, with a malignant progression rate of 8.4%, higher among patients with HIV. The risk of progression was evaluated only according to the clinical appearance of OPMD, while no data about OPMDs histopathological diagnosis, wait-and-see or treatment policies, and treatment type were reported. This seems to suggest that the clinical diagnosis might suffice to assess the risk of malignant transformation of OPMDs independently from treatment and histopathological grading. While knowing the grade of dysplasia might be unnecessary to define the risk of transformation, we believe that whether and how OPMD is treated (particularly leukoplakia and erythroplakia) is likely to be associated with the risk of transformation; thus, missing this information somewhat weakens the conclusion of the authors. Furthermore, the association between smoking and progression to oral cavity cancer deserves clarification. Literature data on this topic are somewhat contradictory: while cigarette smoking is an established risk factor for OPMD occurrence, it is often reported that oral leukoplakia is more aggressive and has a more often unfavorable outlook (eg, increased rate of progression to cancer) among those who do not smoke,2 which contradicts the findings of Villa and colleagues.1 However, more clinically relevant than a patient’s history (eg, lifetime smoking habits [ever/never smoker] or smoked pack-years) is what happens after diagnosis, as this is potentially actionable by the treating physicians. In this regard, literature data consistently show that patients with oral leukoplakia who actively smoke at diagnosis and succeed in quitting have a reduced rate of recurrence and progression to cancer compared with those who continue to smoke.3,4 For instance, Vladimirov et al5 reported that among 51 patients with oral leukoplakia or erythroplakia, the odds of unfavorable events (recurrent lesions, new lesions, or cancer) among those who continued to smoke (69%) was more than 23 times greater than among those who quit smoking (31%).5 The evidence available to date remains limited, particularly for OPMDs other than leukoplakia; thus, more research on the topic is warranted. Yet, the necessity to integrate smoking cessation support into the clinical treatment of these patients appears indisputable, also considering the countless benefits beyond those associated with oral health.