Simple SummaryUsually: statins are prescribed to lower cholesterol levels. Besides, various studies showed that statins have beneficial effects on cancer prevention and treatment. We investigated the effect of statin medication in patients with head and neck cancer in a real-world cohort from a federated network of more than 80 healthcare organizations. We created two cohorts diagnosed with head and neck cancer, with similar age, sex, and risk factors like alcohol and nicotine. Cohort I received statins and cohort II did not. Both cohorts contained about 50,000 patients. We performed a survival analysis and found five-year survival was to be significantly higher for cohort I and a lower risk of death, respectively. As our analysis was conducted retrospectively, the results need further clinical research to be confirmed.AbstractIntroduction: The overall survival among head and neck cancer patients is still low, even in a time of new therapy regimes. Regarding cancer patients’ survival, statin use has already proven to be associated with favorable survival outcomes. Our objective was to investigate the influence of statin medication on the overall survival of head and neck cancer patients. Methods: Retrospective clinical data of patients diagnosed with head and neck cancer (International Classification of Diseases codes: C00–C14) were retrieved from a real-world evidence database. The initial cohort was divided into patients with statin medication, who were assigned to building cohort I, and subjects without statin medication, who were assigned to cohort II, both matched by age, gender, and risk factors (nicotine and alcohol abuse/dependence). Subsequently, Kaplan–Meier and risk analyses were performed, and odds and hazard ratios were calculated. Results: After matching, each cohort contained 48,626 patients (cohort I = females: 15,409; (31.7%), males 33,212 (68.3%); mean age ± standard deviation (SD) at diagnosis 66.3 ± 11.4 years; cohort II = females: 15,432; (31.7%), males 33,187 (68.2%); mean age ± standard deviation (SD) at diagnosis 66.4 ± 11.5 years). Five-year survival was found to be significantly higher for cohort I, with 75.19%, respectively 70.48% for cohort II. These findings were correlated significantly with a risk of death of 15.9% (cohort I) and 17.2% (cohort II); the odds ratio was 0.91 (95% CI: 0.881–0.942) and the hazard ratio 0.80 (0.777–0.827). Conclusions: The results indicate that the five-year survival of head and neck cancer patients is significantly improved by statin medication. As this study was conducted retrospectively, our data must be interpreted with caution, especially since other potential influencing factors and the initial tumor stage were not available.