Research in context
Evidence before this study
Since 2007, 99 countries and territories have introduced human papillomavirus (HPV) vaccination programmes. In 2015, we did a systematic review and meta-analysis to examine the real-world population-level impact of HPV vaccination. The meta-analysis showed substantial decreases in HPV 16 and HPV 18 infections and anogenital wart diagnoses among women targeted for vaccination, and evidence of herd effects among boys and older women, 4 years after the introduction of HPV vaccination. However, at the time of the meta-analysis, the number of years post-vaccination was insufficient to examine the impact of HPV vaccination on cervical intraepithelial neoplasia grade 2+ (CIN2+). Moreover, in 2016, the WHO Strategic Advisory Group of Experts on Immunization revised its position to recommend HPV vaccination of multiple age cohorts of girls, rather than vaccination of a single cohort.
We updated our previous systematic review and meta-analysis to: (1) update and summarise the most recent evidence about the population-level impact of girls-only HPV vaccination on HPV infections and anogenital wart diagnoses among girls, boys, women, and men; (2) summarise new evidence about the population-level impact of girls-only HPV vaccination on CIN2+ occurrence among screened girls and women; and (3) compare the population-level impact of HPV vaccination on anogenital wart diagnoses and CIN2+ occurrence between countries that have implemented either a single or a multiple age-cohort vaccination strategy. We searched MEDLINE and Embase for studies published between Feb 1, 2014, and Oct 11, 2018, with the same combination of MeSH terms, title, or abstract words: (“papillomavirus vaccine”, “papillomavirus vaccination”, “HPV vaccine”, or “HPV vaccination”) and (“program evaluation”, “population surveillance”, “sentinel surveillance”, “incidence”, or “prevalence”), and (“papillomavirus infection”, “condylomata acuminata”, “anogenital warts”, “cervical intraepithelial neoplasia”, “cervical dysplasia”, “uterine cervical neoplasm”, or “HPV related diseases”). We identified 1702 potentially eligible articles for this systematic review and meta-analysis, and included 65 articles in 14 high-income countries: 23 for HPV infection, 29 for anogenital warts, and 13 for CIN2+. We contacted all corresponding authors of eligible studies to request a re-analysis of their data using the same data stratification to allow comparison between studies and pooling.
Added value of this study
The current updated systematic review and meta-analysis, which includes data from 60 million individuals and up to 8 years of post-vaccination follow-up, shows compelling evidence of the substantial impact of HPV vaccination programmes on HPV infections, anogenital wart diagnoses, and CIN2+ among women, and herd effects among boys and older women. Our study also shows greater and faster direct impact and herd effects in countries with multiple age-cohort vaccination and high vaccination coverage, compared with countries with single age-cohort vaccination or low routine vaccination coverage. To our knowledge, our study is the first to present pooled estimates of the population-level impact of HPV vaccination on CIN2+ (the most proximal outcome to cervical cancer), and the first to show the real-world additional benefit of vaccinating multiple age cohorts of girls with high vaccination coverage.
Implications of all the available evidence
Our results provide strong evidence of HPV vaccination working to prevent cervical cancer in real-world settings, as both the cause (high-risk HPV infection) and proximal disease endpoint (CIN2+) are significantly declining. In terms of global policy implications, these results reinforce the recently revised position of WHO recommending HPV vaccination of multiple age cohorts of girls, and provide promising early signs that the WHO call for action on cervical cancer elimination might be possible if sufficient population-level vaccination coverage can be reached.