Updated systematic review and meta-analysis of data from 60 million individuals and up to 8 years of post-vaccination follow-up show compelling evidence of the substantial impact of human papillomavirus (HPV) vaccination programmes on HPV infections and cervical intraepithelial neoplasia grade 2+ (CIN2+) among girls and women, and on anogenital warts diagnoses among girls, women, boys, and men. In addition, programmes with multi-cohort vaccination and high vaccination coverage had a greater direct impact and herd effects. The results are published on 26 June 2019 in The Lancet.
The HPV Vaccination Impact Study Group wrote in the background that more than 10 years have passed since HPV vaccination was implemented. They performed a systematic review and meta-analysis of the population-level impact of vaccinating girls and women against HPV on HPV infections, anogenital wart diagnoses, and CIN2+ to summarise the most recent evidence about the effectiveness of HPV vaccines in real-world settings and to quantify the impact of multiple age-cohort vaccination.
The authors searched MEDLINE and Embase for studies published between 1 February 2014 and 11 October 2018. Studies were eligible if they compared the frequency, either prevalence or incidence of at least one HPV-related endpoint defined as genital HPV infections, anogenital wart diagnoses, or histologically confirmed CIN2+ between pre-vaccination and post-vaccination periods among the general population and if they used the same population sources and recruitment methods before and after vaccination.
Primary assessment was the relative risk (RR) comparing the frequency of HPV-related endpoints between the pre-vaccination and post-vaccination periods.
The study team stratified all analyses by sex, age, and years since introduction of HPV vaccination. They used random-effects models to estimate pooled RRs.
In total, 1702 potentially eligible articles have been identified but at the end, the authors included 65 articles from 14 high-income countries: 23 for HPV infection, 29 for anogenital warts, and 13 for CIN2+.
After 5–8 years of vaccination, the prevalence of HPV 16 and 18 decreased significantly by 83% (RR 0.17) among girls aged 13–19 years, and decreased significantly by 66% (RR 0.34) among women aged 20–24 years. The prevalence of HPV 31, 33, and 45 decreased significantly by 54% (RR 0.46) among girls aged 13–19 years. Anogenital wart diagnoses decreased significantly by 67% (RR 0.33) among girls aged 15–19 years, decreased significantly by 54% (RR 0.46) among women aged 20–24 years, and decreased significantly by 31% (RR 0.69) among women aged 25–29 years.
Among boys aged 15–19 years anogenital wart diagnoses decreased significantly by 48% (RR 0.52) and among men aged 20–24 years they decreased significantly by 32% (RR 0.68).
After 5–9 years of vaccination, CIN2+ decreased significantly by 51% (RR 0.49) among screened girls aged 15–19 years and decreased significantly by 31% (RR 0.69) among women aged 20–24 years.
This updated systematic review and meta-analysis show compelling evidence of the substantial impact of HPV vaccination programmes among girls, women, boys, and men.
The study was funded byWorld Health Organization (WHO), Canadian Institutes of Health Research, Fonds de recherche du Québec – Santé.
A modelling study for global elimination of cervical cancer
Cervical screening and HPV vaccination have been implemented in most high-income countries. However, coverage is low in low- and middle-income countries (LMICs). In 2018, the Director-General of WHO announced a call to action for the elimination of cervical cancer as a public health problem.
In a paper published earlier this year in The Lancet Oncology, the researchers reported findings from a statistical analysis of existing trends in cervical cancer worldwide by using high-quality cancer registry data included in the Cancer Incidence in Five Continents series published by the International Agency for Research on Cancer. They then used a comprehensive and extensively validated simulation platform, Policy1-Cervix in order to predict the future incidence rates and burden of cervical cancer. They presented data globally, by Human Development Index (HDI) category, and at the individual country level.
Overall, the study shows that more than 44 million women will be diagnosed with cervical cancer in the next 50 years if primary and secondary prevention programmes are not implemented in LMICs.
If high coverage of HPV vaccination can be implemented quickly, a substantial effect on the burden of disease will be seen after three to four decades, but nearer-term impact will require delivery of cervical screening to older cohorts who will not benefit from HPV vaccination.
Widespread coverage of both HPV vaccination and cervical screening from 2020 onwards has the potential to avert up to 12.5–13.4 million cervical cancer cases by 2069, and could achieve average cervical cancer incidence of around four per 100 000 women per year or less, for all country HDI categories, by the end of the century.
The study was funded by the National Health and Medical Research Council (NHMRC) Australia, part-funded via the NHMRC Centre of Excellence for Cervical Cancer Control.
References
Drolet M, Bénard É, Pérez N, et al. Population-level impact and herd effects following the introduction of human papillomavirus vaccination programmes: updated systematic review and meta-analysis. Lancet 2019;pii: S0140-6736(19)30298-3. doi: 10.1016/S0140-6736(19)30298-3.
Simms KT, Steinberg J, Caruana M, et al. Impact of scaled up human papillomavirus vaccination and cervical screening and the potential for global elimination of cervical cancer in 181 countries, 2020–99: a modelling study. Lancet Oncol 2019; 20(3):394-407. doi: 10.1016/S1470-2045(18)30836-2.