Population-based age-period-cohort analysis of declining Human Papillomavirus prevalence.

Background: Most countries in the world have launched human papillomavirus (HPV) vaccination programmes and declining prevalences of HPV are reported. We aimed to disentangle the influences of calendar time, birth cohort and age by analysing HPV prevalences in the population-based cervical screening programme using age-period-cohort modelling.

Methods: All 836,314 primary HPV-based cervical screening tests from women aged 23-64 between 2014-2023 in the capital region of Sweden were identified in the Swedish National Cervical Screening Registry. The odds ratio of HPV16/18 infection was estimated comparing each birth cohort to the unvaccinated 1984-born using an age-period-cohort model. The impact of changing HPV prevalences on the numbers needed to screen (NNS) to detect and prevent 1 cervical cancer case were calculated.

Results: HPV vaccination coverage was 82-83% among women born in 1999-2000. Before 2019 the HPV16/18 prevalence was highest among the youngest women in the screening program. During 2020-2023 the prevalence consistently decreased among the birth cohorts offered organised school-based vaccination. There was a 98% decline in HPV16 prevalence (odds ratio=0.02 [95% CI 0.01-0.04]) and a 99% decline in HPV18 prevalence (odds ratio=0.01 [0.00-0.04]) among the 2000-born compared to the HPV unvaccinated 1984-born. The declining HPV16/18 prevalences resulted in major increases in the NNS to detect and to prevent 1 case of cervical cancer.

Conclusions: The declines of HPV16/18 were considerably larger than the vaccination coverage, suggesting herd immunity effects. The changing epidemiology of HPV types impacts screening needs, necessitating updated screening programs.