BACKGROUND: Head and neck cancers (HNCs) encompass a heterogeneous group of cancers between the mouth and larynx. Familial clustering in HNCs has been described, but how it influences individual sites and to which extent known risk factors, such as human papilloma virus (HPV) infection, may contribute is not well established. PATIENTS/METHODS: We employed standardized incidence ratios (SIRs) to estimate familial risks for HNC with same (concordant) and different (discordant) cancers among first-degree relatives using data from the Swedish Cancer Registry from 1958 to 2018. RESULTS: Incidence for male and female oropharyngeal cancer increased close to four-fold in the past 39 years. Familial HNC was found in 3.4% of the study population, with an overall familial SIR of 1.78. Patients with concordant nasopharyngeal cancer showed a high risk of 23.97, followed by hypopharyngeal cancer (5.43). The husbands of wives with cervical cancer had an increased risk of oropharyngeal cancer. DISCUSSION/CONCLUSION: Nasopharyngeal cancers lacked associations with lifestyle or HPV associated cancers, suggesting a role for germline genetics, which was also true for the high-risk families of three HNC patients. In the Swedish population with low smoking levels, HPV is becoming a dominant risk factor, emphasizing the need for sexual hygiene and HPV vaccination.

Cancer Gene Therapy Group Translational Immunology Research Program University of Helsinki 00029 Helsinki Finland

Center for Community based Healthcare Research and Education Department of Functional Pathology School of Medicine Shimane University Izumo Shimane 693 8501 Japan

Center for Primary Health Care Research Lund University 20502 Malmö Sweden

Department of Family Medicine and Community Health Department of Population Health Science and Policy Icahn School of Medicine at Mount Sinai New York NY 10029 USA

Department of Otorhinolaryngology Head and Neck Surgery Helsinki University Hospital and University of Helsinki 00029 Helsinki Finland

Department of Urology Helsinki University Hospital and University of Helsinki 00029 Helsinki Finland

Division of Cancer Epidemiology German Cancer Research Centre 69120 Heidelberg Germany

Division of Pediatric Neurooncology German Cancer Research Center 69120 Heidelberg Germany

Faculty of Medicine and Biomedical Center in Pilsen Charles University Prague 30605 Pilsen Czech Republic

Hopp Children's Cancer Center 69120 Heidelberg Germany

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