Association between HPV vaccination and cervical screening policy changes and cervical cancer incidence and grade-3 cervical intraepithelial neoplasia incidence in England, 2006-2020: a population-based trends analysis.

Background: Monitoring trends in diseases after the implementation of new public health interventions or policy changes is crucial for public health planning and surveillance. In this study we look at variations in rates of cervical cancer and grade-3 cervical intraepithelial neoplasia (CIN3) incidence between 2006 and 2020 in England and relate them to predictions based on the changes in HPV vaccination and cervical screening policy. Methods: Using population-based registry data, we estimated incidence rates and their 95% confidence intervals for cervical cancer and CIN3 by age group and by either year of diagnosis or 1-year birth cohort. Trends were compared over time and across birth cohorts by calculating relative changes with respect to reference time points. We also tested if trends in women offered HPV vaccination were significantly different across outcomes (cervical cancer and CIN3) and age groups. To do this, we used Poisson regression with adjustments for interval censoring, overdispersion and correlation between observations. Findings: There were 5558 cancers and 164,682 cases of CIN3 from 53.4 million women-years of observation in the age group 20-29.99 years. We found no evidence of increased cervical cancer rates over the age of 26 in cohorts not offered cervical screening until age 24.5 or 25 years. Substantial and increasing reductions in CIN3s and cervical cancers were observed in the cohorts offered HPV vaccination and were consistent with an 80% (95% CI: 72.9%-87.1%) decrease in cervical neoplasia in the routine vaccination group. Interpretation: Plots against different time scales (e.g., calendar year and date of birth) may provide important insights that could otherwise be missed. Our findings are consistent with a sustained high effectiveness of the HPV immunization programme as the catch-up vaccination cohorts age. Funding: Cancer Research UK.