- New England Journal of Medicine
Risk of oral cancer can be predicted by the DNA content cells of oral leukoplakia, the most common premalignant lesion of the oral cavity. This finding marks an important advance in the molecular assessment of risk of oral carcinoma in patients with these white patches in their mouths. Such new molecular data have important implications for the standard of care these patients, redefining assessment of the risk and even helping to guide treatment.
Oral cancer is the most common neoplasm of the head and neck, with an annual worldwide incidence of new cases exceeding 400,000. However, the five-year survival rate of less than 50 percent has not improved in more than two decades. Risk factors for oral carcinoma have previously been identified. Until now, there have been no reliable predictors of the outcome in individual patients with oral leukoplakia, which may develop into squamous-cell carcinoma. Participants in this study were 150 patients with oral leukoplakia classified as epithelial dysplasia. Researchers measured the nuclear DNA content (ploidy) of the lesions to determine whether DNA ploidy could be used to predict clinical outcome. Patients were followed for a mean of 8.6 years.
The DNA content was found to be a powerful predictor of risk of malignant transformation at the site of the lesion. Of the dysplastic leukoplakias, 70 percent were low-risk diploid lesions, three percent of which progressed to cancer, 13 percent were intermediate-risk tetraploid lesions, 60 percent of which progressed to cancer; and 17 percent were high-risk aneuploid lesions, 84 percent of which progressed to cancer. In other studies of molecular markers of risk in leukoplakia, risk was inversely linked with the time to malignant transformation. Ploidy status, or level of risk, was relatively stable over the course of the studies. Degree of dysplasia did not correlate with DNA content or risk of cancer. Cumulative disease-free survival rate was 97 percent among those with diploid lesions, 40 percent in those with tetraploid lesions and 16percent in the aneuploid lesions group.