Malignant Transformation Rate of Non-reactive Oral Hyperkeratoses Suggests an Early Dysplastic Phenotype

The presence of epithelial dysplasia (ED) in oral leukoplakia is the single most important predictor of malignant transformation (MT). The majority of leukoplakias, however, do not show evidence of ED and yet MT of these lesions is well-recognized. These lesions have been referred to as "hyperkeratosis/hyperplasia, no dysplasia," "keratosis of unknown significance" and "hyperkeratosis, not reactive (HkNR)." This study evaluates the MT rate of such leukoplakias. A literature review was performed to identify cohort studies on leukoplakias where (1) there was a recorded histopathologic diagnosis, (2) cases of "hyperkeratosis/hyperplasia, no dysplasia" comprised part of the cohort, and (3) follow-up information was available. There were 9,358 leukoplakias, of which 28.5% exhibited ED while 37.7% consisted of HkNR. Follow-up ranged from 15 to 73 months. The incidence of MT in leukoplakia exhibiting HkNR was 4.9%, compared to 15.3% for ED. Among oral squamous cell carcinomas (SCC) with previously biopsied, site-specific precursor lesions, 55.7% arose from ED/carcinoma in situ and 28.0% arose from HkNR. Leukoplakia exhibiting HkNR has a substantial MT rate, similar to that of mild ED, and must be recognized and managed appropriately to reduce oral SCC incidence.