Published in the Lancet Primary Care, researchers from NDORMS at the University of Oxford and collaborators across Norway, Spain and the UK designed an observational study to estimate the long-term effectiveness of HPV (human papilloma virus) vaccination to prevent high-grade cervical pre-cancerous lesions and cervical cancer, in the broad context of Europe’s Beating Cancer Plan initiative to eliminate cancers caused by HPV by 2030.
Their results were compared to randomised controlled trials, which have previously demonstrated that HPV vaccination reduces the risk of high-grade cervical pre-cancerous lesions.
Using electronic health and national registry data from more than 330,000 women across Norway, Spain and the UK, researchers applied multiple methodological approaches to strengthen the robustness and reliability of their findings. These included the use of a ‘target trial emulation’ framework, which uses real-world data (data captured under real-world conditions, such as hospitals or primary care centres), to replicate the design of a randomised controlled trial, which is the gold standard for establishing the performance of a vaccine (and other medical products).
In this study, women vaccinated before the age of 15 were compared with matched unvaccinated peers with similar demographic and health characteristics. This design allowed the researchers to estimate vaccine effectiveness over up to 15 years of follow-up under real-world conditions. The results showed a substantial reduction in high-grade cervical pre-cancerous lesions and related surgical treatment among vaccinated women compared with those who were unvaccinated. The effectiveness against cervical cancer could not be assessed. Cervical cancer typically occurs in women aged 40 years or older, and the study participants were still too young at the time of analysis. However, the natural history of cervical cancer suggests that preventing the risk of precancerous lesions will lead to protection against cervical cancer.
Marta Alcalde Herraiz, DPhil student in Clinical Epidemiology and Medical Statistics at NDORMS and Data Scientist of the study, said: ‘Our study provides reassurance that well-designed observational studies can effectively complement clinical trials findings for the study of vaccine effectiveness after approval and use in the community.’
Daniel Prieto-Alhambra, Professor of Pharmaco- and Device Epidemiology at NDORMS and Deputy Director of the DARWIN EU Coordination Centre (Erasmus MC), said: ‘These findings have important implications for public health decision-making. They support the use of high-quality observational studies to monitor long-term vaccine impact, complement clinical trial evidence, and inform decision making. It demonstrates how European real-world data can be used to provide reliable evidence on vaccine effectiveness at population scale.’