HPV-Related Cancers in Solid Organ Transplant Recipients: A Nationwide Danish Cohort Study

Human papillomavirus (HPV) is a major cause of several epithelial cancers. Solid organ transplant recipients (SOTRs) are chronically immunosuppressed, but population-based estimates of HPV-related cancer risk across transplanted organs and by sex remain limited. We conducted a nationwide, population-based cohort study including all SOTRs in Denmark from January 1, 2000, to December 31, 2023. Information on transplantation and cancer diagnoses was obtained from the Danish National Patient Registry. Each SOTR was matched with five population controls by age, sex, and birth cohort. Incidence rates and hazard ratios (HRs) for HPV-related cancers were estimated using Cox proportional hazards models, and cumulative incidence was calculated using the Aalen-Johansen method. The cohort comprised 6509 SOTRs and 32,545 matched controls, followed for a median of 7.8 years (IQR 3.8-13.1). The 10-year incidence rate of HPV-related cancers was higher among SOTRs than controls (0.10 [95% CI 0.08-0.14] vs. 0.04 [95% CI 0.03-0.05] per 100 person-years). The overall HR for any HPV-related cancer was 2.49 (95% CI 1.74-3.56) and was highest for anogenital cancers (HR 3.29; 95% CI 1.88-5.76). Relative risks were higher among women than men (HR 3.11 [95% CI 1.77-5.46] vs. 2.15 [95% CI 1.35-3.43]), with cumulative incidence indicating earlier onset among women. Solid organ transplant recipients experience a sustained two-to-three-fold increased risk of HPV-related cancers, with pronounced sex-specific differences. These findings provide robust population-level evidence of elevated long-term cancer risk in immunosuppressed individuals.