Human papillomavirus-associated cancers, precancers, and genital warts in Denmark, 2000-2022 - Current burden of disease and population impact of multi-cohort HPV vaccination

Objectives: We present incidence trends of cancer and precancer at human papillomavirus(HPV)-associated sites, and genital warts, including the current burden of HPV-associated disease in Denmark, a country with multi-cohort HPV vaccination.

Method: Cases were identified from high-quality nationwide registries (2000-2022). The age-specific incidence rate, age-standardized incidence rate (ASR) and estimated annual percentage change (EAPC) were calculated according to sex and calendar year. The current burden (2020-2022) of HPV-associated disease was estimated as the average annual number of each lesion multiplied by the disease-specific HPV-attributable fraction.

Results: ASRs of cervical precancer and genital warts declined markedly in the post-HPV vaccination period - for genital warts corresponding to an EAPC of -13.7 % (-15.0;-12.4)(women) and -8.8 % (-9.4;-8.2)(men), respectively. ASRs of HPV-associated cancer sites increased continuously in men (EAPC: 2.8 % (2.2;3.5)), and the same was observed for non-cervical HPV-associated cancer sites in women (EAPC: 2.5 % (2.0;3.0)). Cervical cancer, however, decreased in the post-HPV vaccination period (EAPC: -2.7 % (-3.8;-1.5)). Age-specific incidence rates of HPV-associated cancer sites decreased slightly in younger women and were stable in younger men, while incidence rates in older men approached or even surpassed that of older women. Data on the current burden showed that cervical precancer and genital warts are still the major contributors to HPV-associated disease, and oropharyngeal cancer now accounts for more annual cases on a population level than cervical cancer.

Conclusion: Danish data show decreased incidence of cervical lesions and genital warts in the post-vaccine era. Despite population impact of HPV vaccination, HPV-associated disease remains a public health issue and increasingly among men.