More than 300,000 new cases worldwide are being diagnosed with
oral squamous cell carcinoma annually. This aggressive epithelial
malignancy is associated with a high mortality and severe morbidity among the long-term survivors. The ability to intervene prior to this advanced stage may improve treatment results. This requires the early identification of molecular events that represent early phases of malignant transition, which is possible through measurement of
DNA ploidy in epithelial cells of
oral leukoplakia. Recently, we showed that patients with
aneuploid dysplastic oral lesions had a 96% rate of
oral cancer (26 of the 27 patients received the diagnosis) with a 70% rate within three years, an 81% rate of subsequent
cancer (22 of 27), a 74% rate of death from
cancer (21 of 27) and virtually no help from complete resection-all hallmarks of biologically aggressive
cancer. Standard treatment of
oral leukoplakia-a precursor lesion of
oral cancer-varies from watchful waiting to complete resection. We have recently demonstrated that complete resection of
aneuploid oral leukoplakia does not prevent the occurrence of clinically aggressive and highly lethal
oral cancer. Oral
carcinogenesis is a complex multifocal process of multiclonal field
carcinogenesis and intraepithelial clonal spread. The multifocal nature of early oral
carcinogenesis may hinder local treatment modalities. Inhibitors of
cyclooxygenase-2 (COX-2) and
epidermal growth factor receptor (EGFR), either alone or in combination, may be used for reversing or stopping the oral
carcinogenesis at an early stage of disease. The failure of standard treatment to control
aneuploid oral leukoplakia justifies clinical trials with new treatment modalities, such as systemic
therapy with molecular targeting agents, which in patients with aggressive
leukoplakia is tantamount to
cancer therapy.