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Background: Our previous research showed that a high rate of secondary carcinogenesis is observed during follow-up after transoral surgery in patients with early-stage laryngeal, oropharyngeal, and hypopharyngeal cancers. We speculate that the contributing factors are alcohol drinking, smoking, and aging; however, we could not provide clear evidence. In this study, we aimed to identify the risk factors for secondary carcinogenesis in patients with these cancers, particularly factors associated with drinking and/or smoking. Methods: The medical records of all-stage laryngeal, oropharyngeal, and hypopharyngeal cancer patients who had undergone definitive treatment were retrospectively analyzed. Assessments included visual and endoscopic observations of the primary site, enhanced cervical CT or US of the primary site and regional lymph nodes, PET-CT, and enhanced whole-body CT. Clinical characteristics were compared in patients with and without secondary carcinogenesis and in patients with hypopharyngeal cancer and patients with other cancers. Results: Hypopharyngeal cancer was an independent risk factor for secondary cancer. The 5-year incidence rate of secondary cancer was 25.5%, 28.6%, and 41.2% in laryngeal, oropharyngeal, and hypopharyngeal cancers, respectively. Radiotherapy was defined as an independent risk factor in hypopharyngeal cancer patients with secondary cancers. No direct correlation was found between secondary carcinogenesis and alcohol consumption, smoking, or aging. Conclusions: Patients with hypopharyngeal cancer require close follow-up as they are at high risk of developing secondary cancer, possibly because out-of-field radiation exposure may induce systemic secondary carcinogenesis in hypopharyngeal cancer patients with genetic abnormality induced by alcohol consumption. [ABSTRACT FROM AUTHOR]