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Patients with head and neck squamous cell carcinoma (HNSCC) are at risk for local and regional relapse, as well as for occurrence of synchronous or metachronous secondary carcinoma. The aim of this retrospective study was to evaluate the frequency of secondary malignancies amongst HNSCC patients and their association with age, sex and TNM classification, as well as smoking and alcohol abuse. Data from 394 patients with HNSCC who were treated at the Department of Otorhinolaryngology-Head and Neck Surgery of the University Hospital Mannheim between 2011 and 2015 were retrieved and analyzed using t-tests and P≤0.05 was considered statistically significant. Of the 394 patients, 50 (12.7%) developed a secondary carcinoma. In this cohort, >70% of secondary malignancies were diagnosed using clinical inspection or microlaryngoscopy. The majority of secondary malignancies were identified in the oropharynx, with men being more often affected overall. Continued abuse of carcinogenic substances appeared to increase the incidence of secondary carcinoma, whereas the localization of the primary tumor, age, sex or TNM classification were not identified as significant indicators of the occurrence of a secondary carcinoma. The purpose of the present study was to emphasize the importance of intensive follow-up to ensure early detection of secondary malignancies. The aim was to help predict numbers and occurrence within smaller cohorts, and to evaluate the quality of data collected during the establishment of a certified tumor center. To fully evaluate the role of continued exposure to noxious substances and other possible contributing factors, and in order to improve the rate of early diagnosis and establish preventive strategies, multicentered studies with larger cohorts are required. [ABSTRACT FROM AUTHOR]