The Association between Infectious Mononucleosis and Cancer: A Cohort Study of 24,190 Outpatients in Germany

SIMPLE SUMMARY: Cancer is one of the leading causes of death worldwide. Besides genetic risk factors and non-communicable diseases, chronic infections, including Epstein–Barr virus (EBV) infection, have been identified as promoters of cancer. The aim of our study was to investigate the association between infectious mononucleosis, the clinical manifestation of EBV infection, and cancer development in a real cohort of outpatients in Germany. Patients diagnosed with infectious mononucleosis were found to have an increased incidence of tumors of the hematopoietic and lymphoid tissues and a strong tendency to have a positive association with prostate cancer. Together, our results support the evidence for a role of EBV in the development of various malignancies and may stimulate further research efforts to elucidate the precise involvement of EBV in the carcinogenic process. ABSTRACT: Background: Cancer represents one of the leading causes of death worldwide. Besides genetic risk factors and non-communicable diseases, chronic infections including Epstein–Barr virus (EBV) infection have been identified as promotors of cancer. In the present manuscript, we evaluated the association between infectious mononucleosis, the clinical manifestation of EBV infection, and cancer development in a real-word cohort of outpatients in Germany. Methods: We used the Disease Analyzer database (IQVIA) and matched a total of 12,095 patients with infectious mononucleosis to a cohort of individuals without infectious mononucleosis based on age, sex, index year, and annual patient consultation frequency between 2000 and 2018. Results: Patients diagnosed with infectious mononucleosis had a cancer incidence of 5.3 cases per 1000 person years versus 4.4 cases per 1000 person years for patients without infectious mononucleosis. In multivariable regression models, infectious mononucleosis showed a trend towards a higher incidence of cancer in general in the age group > 50 years (incidence rate ratio (IRR): 1.32; 95% CI: 1.04–1.67) and among men (IRR: 1.36; 95% CI: 1.07–1.72). Infectious mononucleosis was significantly associated with an increased incidence of tumors of the hematopoietic and lymphoid tissues (IRR: 1.75; 95% CI: 1.22–2.50) and showed a strong trend towards an association with prostate cancer (IRR: 3.09; 95% CI: 1.23–7.76). Conclusion: Infectious mononucleosis is associated with an increased incidence of certain cancer types. The present data from a large real-world cohort support the evidence on a role of EBV in the development of different malignancies and could trigger research efforts to further elucidate its precise involvement in the carcinogenic process.