Radiotherapy for oral cancer as a risk factor for second primary cancers

Radiation exposure, known to cause DNA damage, may be a potential source of field cancerization of the upper aerodigestive tract. Radiotherapy for head and neck cancers has been examined as a possible risk factor for second primary cancers, but the results have been equivocal. We evaluated the impact of therapeutic radiation for oral cancer on the risk of second primary cancers with data from the Surveillance, Epidemiology, and End Results (SEER) program for 1973-1999. Among 30,221 first primary oral squamous cell carcinoma patients, 6163 (20.4%) patients developed a second primary cancer, 5042 of which were metachronous. Patients treated with radiation only (RR=1.64, 95%CI=1.18-2.29) or radiation with surgery (RR=1.49, 95%CI=1.07, 2.06) had elevated risks of developing a second primary tumor, whereas patients treated with surgery only did not appear to be at increased risk (RR=1.28, 95%CI=0.93, 1.76). Consistent with an expected latent period between radiation exposure and tumor occurrence, radiation became a risk factor after 10 years of follow-up for solid cancers of the oral cavity (RR=2.8, 95%CI=1.5, 5.2), pharynx (RR=5.9, 95%CI=1.7, 20.7), esophagus (RR=3.9, 95%CI=1.1, 13.4) and lung (RR=1.5, 95%CI=1.0, 2.4), and after 1-5 years of follow-up for second primary leukemia (RR=2.5, 95%CI=1.0, 6.7). Radiotherapy for oral cancer appears to be a risk factor for second primary tumors. Further studies that account for chemotherapy and examine frequency and duration of radiotherapy would be of interest in confirming the observed association.