Background: Second primary cancer is prevalent in patients with head and neck cancer (HNC), for which esophagus and lung are the most usual sites, associated with an extremely poor prognosis. However, information regarding the actual risk of second primary esophageal or lung cancer in South-east Asia, the betel-quid chewing area, has been restricted to data from single-institutions. We have therefore conducted a population-based study to evaluate the incidence, risk, and developmental time of second esophageal or lung cancer in HNC patients. Methods: Standardized incidence ratios (SIRs) and cumulative incidences were calculated for second primary esophageal or lung cancer using a database from the Taiwan Cancer Registry that included 63,720 cases having an initial diagnosis of HNC. Results: The risk of second esophageal cancer was increased in patients with oral/pharyngeal (SIR = 8.71, 95% CI 7.55-10.01) and laryngeal (SIR = 4.65, 95% CI 3.37-6.27) cancers, whereas second lung risk was increased in patients with laryngeal (SIR = 2.05, 95% CI 1.69-2.45) and oral/pharyngeal (SIR = 1.56, 95% CI 1.34-1.80) cancers. The risk excess was prominent for patients with a follow-up interval <5 years and a first primary cancer diagnosed at age <50. Nevertheless, patients with nasopharyngeal carcinoma were not associated with an excess risk in second esophageal or lung cancer. Conclusions: The present dataset provides definite evidence that there is a substantial excess risk of second primary esophageal or lung cancer for the index tumors of oral cavity, pharynx and larynx. The absence of risk excess found in nasopharyngeal carcinoma is also compatible with the existing knowledge that it might have an entirely distinctive etiology.
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