Cervical cancer mortality trends following HPV vaccination in England, 2001-24: an analysis of population-based mortality data.
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BACKGROUND: Human papillomavirus (HPV) vaccination is a key component of global cervical cancer elimination strategies. While substantial declines in cervical cancer incidence have been observed in several countries, evidence of its effect on mortality is scarce. England introduced a national HPV vaccination programme in 2008 for girls aged 12-13 years (achieving 80-90% coverage before the COVID-19 pandemic), with a catch-up campaign in 2008-10 for girls aged 14-18 years. We aimed to investigate trends in cervical cancer mortality and to estimate the reduction in cervical cancer deaths in young women in England following the introduction of HPV vaccination. METHODS: We analysed population-based cervical cancer mortality data from England between 2001 and 2024 among women aged 20-24, 25-29, and 30-34 years. HPV vaccination coverage by birth cohort was obtained from official reports and used to estimate, for each age group and calendar year of death, the proportion of women who had been vaccinated. We plotted observed and adjusted age-specific mortality rates against year of death and overlaid a smoothed curve. Poisson regression applied to the numbers of deaths was used to estimate the relative risk reduction in vaccinated women compared with what was expected in the absence of vaccination, assuming no herd immunity. Confidence intervals were obtained by inverting the likelihood ratio test. FINDINGS: In women aged 20-24 years between 2020 and 2024, in whom vaccination coverage was around 88-90% at age 12-13 years, no deaths occurred, compared with 23·1 expected deaths based on historical rates, corresponding to a mortality reduction of 100% (95% CI 84-100). In earlier birth cohorts, who were offered vaccination up to age 18 years with coverage of around 63-87%, mortality reductions of 80% (51-94) in women aged 20-24 years in 2015-19, and 69% (55-79) in women aged 25-29 years in 2020-24 were observed. The relative risk reduction in vaccinated women was estimated from population-level data to be 100% (95% CI 81 to 100) in women aged 20-24 years, 100% (89 to 100) in those aged 25-29 years, and 63% (-13 to 100) in those aged 30-34 years. Up until the end of 2024, HPV vaccination in England was associated with a reduction of around 199·6 cervical cancer deaths (95% CI 125·0-274·2). INTERPRETATION: Our findings provide the first robust national-level evidence, albeit observational, that high HPV vaccination coverage is associated with a substantial reduction in cervical cancer deaths. This is shown by the substantial decrease in cervical cancer deaths observed among women aged 20-29 years in England, particularly among those vaccinated at ages 12-13 years. These findings support the achievability of the WHO goal of eliminating cervical cancer as a public health problem, and efforts should be made to achieve high vaccine uptake among young adolescents globally. FUNDING: Cancer Research UK.