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This article has been retracted at the request of Oral Oncology and the co-authors. Please see http://www.elsevier.com/locate/withdrawalpolicy . Reason: The lead author, Jon Sudbo, has been found by the Investigating Commission (appointed in January 2006 by Rikshospitalet - Radiumhospitalet MC and the University of Oslo to investigate Dr Sudbo's misconduct) to have fabricated and modified the data on which the analyses were based. The above mentioned Investigating Commission has determined that Dr Sudbo acted alone in fabricating the data. Dr Sudbo disputes the findings of the Investigating Commission. Reference: Ekbom A, Helgesen GEM, Lunde T, Tverdal A, Vollset SE, Simonsen S. Report from the Investigating Commission appointed by Rikshospitalet - Radiumhospitalet MC and the University of Oslo, January 18, 2006.

Emerging data indicate a link between genetic instability and up-regulation of cyclooxygenase-2 (COX-2). To see if individuals at high risk of oral cancer are candidates for treatment with selective COX-2 inhibitors (coxibs), levels of COX-2 expression in healthy, premalignant and cancerous oral mucosa were compared with the occurrence of DNA ploidy status as a genetic risk marker of oral cancer. COX-2 gene product was evaluated immunohistochemically in 30 healthy persons, in 22 patients with dysplastic lesions without previous or concomitant carcinomas, and in 29 patients with oral carcinomas. The immunohistochemical findings were verified by western blotting. COX-2 expression was correlated to DNA content as a genetic risk marker of oral cancer. COX-2 was up-regulated from healthy to premalignant to cancerous oral mucosa. Thus, COX-2 expression was found in 1 case of healthy oral mucosa (3%). All specimens from healthy mucosa had a normal DNA content. In patients with premalignancies. In 29 patients with oral carcinomas, cyclooxygenase-2 expression was observed in 26 (88%), and aneuploidy was observed in 25 cases (94%, P=0.04). Notably, of 22 patients with dysplastic lesions, COX-2 was exclusively expressed in a subgroup of nine patients (41%) identified to be at high risk of cancer by the aberrant DNA content of their lesions. Seven of these patients were followed for 5 years or more. An oral carcinoma developed in six of them (85%; P=0.02). These findings emphasize the need to determine whether coxibs can reduce the risk of oral cancer in patients with high-risk precancerous lesions.

Given the increase in the age distribution of the population, an increase in cancer incidence rates are to be expected. Oral cancer is a disfiguring disease that continues to increase in incidence, particularly in the young, and to an extent that cannot be fully explained by increased exposure to known risk factors. Despite extensive research on treatment modalities towards oral cancer, the 5-year survival rate of this disease has not been improved over the last 4-5 decades. These facts strongly favour chemoprevention-systemic medication to revert, stop, or delay the carcinogenic process-as an approach to treating oral cancer. A chemopreventive approach to oral cancer most likely should encompass a combination of drugs targeting metabolic pathways relevant to oral carcinogenesis. Candidate drugs are retinoids and selective inhibitors of cyclooxygenase-2, epidermal growth factor receptor (EGFR), and peroxisome proliferator activated receptors (PPARs). Chemopreventive trials so far have used surrogate intermediate biomarkers as measurement of treatment effect. However, the efficiency of any drug for chemopreventive use should be assessed through a prospective randomized trial and evaluated by the only definitive end point for prevention of cancer, the incidence rates of new carcinomas.

Emerging data indicate a link between genetic instability and up-regulation of cyclooxygenase-2 (COX-2). To see if individuals at high risk of oral cancer are candidates for treatment with selective COX-2 inhibitors (coxibs), levels of COX-2 expression in healthy, premalignant and cancerous oral mucosa were compared with the occurrence of DNA ploidy status as a genetic risk marker of oral cancer. COX-2 gene product was evaluated immunohistochemically in 30 healthy persons, in 22 patients with dysplastic lesions without previous or concomitant carcinomas, and in 29 patients with oral carcinomas. The immunohistochemical findings were verified by western blotting. COX-2 expression was correlated to DNA content as a genetic risk marker of oral cancer. COX-2 was up-regulated from healthy to premalignant to cancerous oral mucosa. Thus, COX-2 expression was found in 1 case of healthy oral mucosa (3%). All specimens from healthy mucosa had a normal DNA content. In patients with premalignancies. In 29 patients with oral carcinomas, cyclooxygenase-2 expression was observed in 26 (88%), and aneuploidy was observed in 25 cases (94%, P=0.04). Notably, of 22 patients with dysplastic lesions, COX-2 was exclusively expressed in a subgroup of nine patients (41%) identified to be at high risk of cancer by the aberrant DNA content of their lesions. Seven of these patients were followed for 5 years or more. An oral carcinoma developed in six of them (85%; P=0.02). These findings emphasize the need to determine whether coxibs can reduce the risk of oral cancer in patients with high-risk precancerous lesions.

The majority of oral squamous cell carcinomas (OSCCs) are preceded by visible changes in the oral mucosa, most often white patches. Although the histological finding of dysplasia in oral white patches signals increased risk of developing OSCC, this may also occur in non-dysplastic lesions. However, no reliable markers exist to predict the occurrence of OSCC in these patients. From a total of 263 patients diagnosed with oral white patches, biopsies from 45 patients were selected on the criteria that the patients had lesions histologically proven to be non-dysplastic. The lesions were analyzed with respect to their DNA content. The clinical outcome of the patients was known from the Cancer Registry of Norway, and these data were compared to the DNA content of their lesions. Among the 45 patients, five cases (11%) later developed an OSCC. Four of the cases that subsequently developed an OSCC were among the five aneuploid (abnormal) cases (P=0.001). One aneuploid lesion did not develop a carcinoma during a follow-up time of 120 months. The fifth case that subsequently developed an OSCC was diploid (normal), and developed into an OSCC after an observation time of 73 months (P=0.001). In conclusion, aberrant DNA content reliably predicts the occurrence of OSCC in patients that otherwise would be regarded as at very low risk. Normal DNA content indicates low risk.