Population-Based Age-Period-Cohort Analysis of Declining Human Papillomavirus Prevalence

Abstract

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

Methods: All 813 882 primary HPV-based cervical screening tests from women aged 23-64 years between 2014 and 2023 in the capital region of Sweden were identified in the Swedish National Cervical Screening Registry. The odds ratio (OR) of HPV-16/18 infection was estimated comparing birth cohorts to the unvaccinated 1984-born using an age-period-cohort model. The impact of changing HPV prevalences on the number needed to screen (NNS) to detect and prevent 1 cervical cancer case was calculated.

Results: HPV vaccination coverage was 82%-83% among women born in 1999-2000. Before 2019, the HPV-16/18 prevalence was highest among the youngest women. During 2020-2023 the prevalence consistently decreased among the birth cohorts offered organized school-based vaccination. There was a 98% decline in HPV-16 prevalence (OR, 0.02 [95% confidence interval {CI}, .01-.04]) and a 99% decline in HPV-18 prevalence (OR, 0.01 [95% CI, .00-.04]) among the 2000-born compared to the 1984-born. The declining HPV-16/18 prevalences resulted in major increases in the NNS to detect and to prevent 1 case of cervical cancer.

Conclusions: The declines of HPV-16/18 were considerably larger than the vaccination coverage, suggesting herd immunity. The changing epidemiology of HPV types impacts screening needs, necessitating updated screening programs.

Keywords: HPV; HPV elimination; HPV prevalence; HPV vaccination; cervical screening; herd protection.

Figure 1.

Flowchart of the repeated cross-sectional study of women attending human papillomavirus–based cervical screening from 2014 through 2023. Abbreviations: HPV, human papillomavirus; NKCx, Swedish National Cervical Screening Registry.

Figure 2.

Lexis diagrams of the human papillomavirus (HPV) vaccination coverage among females residing in Sweden from 2005 to 2023 (A), and HPV-16 prevalence (B) and HPV-18 prevalence (C) among women attending cervical screening in the Stockholm region.

Figure 3.

Estimated odds ratios (95% confidence intervals [CIs]) comparing the odds of human papillomavirus (HPV) type 16 and 18 positivity among birth cohorts relative to the 1984 birth cohort (the reference cohort where HPV vaccination coverage was negligible), as estimated via the age-period-cohort model plotted against the HPV-unvaccinated percentage (1 minus the HPV vaccination coverage) of women in Sweden. The shaded area around the line represents the 95% CIs.