Which putatively pre‐malignant oral lesions become oral cancers?

Oral squamous cell carcinomas continue to be a group of diseases with high mortality and increasing incidence rates, particularly among young individuals. This is a paradox finding, since most oral cancers are preceded – even by several years – by readily detectable mucosal changes, most often white or red patches (leukoplakias and erythroplakias, respectively). However, only a small fraction of leukoplakias or erythroplakias are related to cancer development, and the challenge has been to identify the high‐risk lesions. From the vast literature on molecular markers in oral pre‐cancer, no reliable prognostic marker for risk assessment in putatively pre‐malignant lesions has emerged. For this reason, a wait‐and‐see approach has been adopted for this group of lesions. Recently published data point to gross genomic aberrations (DNA aneuploidy) as a tool for targeting patients at particular risk for future cancerous lesions in the oral cavity. Thus, DNA aneuploidy signalled a very high risk for subsequent development of carcinomas in a wide range of lesions from the oral mucous membrane, ranging from oral leukoplakias to oral erythroplakias and even including lesions that had been explicitly defined as being without a malignant potential by a group of trained pathologists. As an extension of research in oral pre‐malignancies, the enzyme cyclooxygenase‐2 (COX‐2) seems to be enhanced specifically in high‐risk oral lesions, as defined by the aberrant DNA content of their lesions. These data strongly indicate that COX‐2 inhibitors (coxibs) should be investigated as chemopreventive agents in patients identified to be at high risk of developing oral cancer.