Research in context
Evidence before this study
Two systematic reviews and meta-analyses have collated population-based data demonstrating early evidence of the effectiveness of the human papillomavirus (HPV) vaccination programme in high-income countries. These studies showed a significant reduction in HPV type 16 and 18 associated with the vaccine. Although reduction in HPV types 31 was suggested, there was no evidence of a reduction in HPV types 31, 33 and 45 as a group. Studies included in these reviews covered both the bivalent and quadrivalent vaccines, had differing levels of vaccine uptake, were often ecological studies comparing prevalence in different timeframes, and were focused on those vaccinated at older ages as part of catch-up cohorts.
On March 8, 2016, we did a PubMed search using the terms (“papillomavirus vaccine”, “papillomavirus vaccination”, “HPV vaccine”, or “HPV vaccination”) and (“program evaluation”, “population surveillance”, “sentinel surveillance”, “incidence”, or “prevalence”), with 151 articles published in the intervening period since the 2015 review paper (from Feb 1, 2014, to March 8, 2016), and found a further six studies, including our own work, reporting population-based HPV prevalence in vaccinated populations from England, Scotland, Sweden, Australia, and the USA (two studies) with all except the UK studies evaluating the impact of the quadrivalent vaccine. The populations studied were generally vaccinated during catch-up campaigns and were attending cervical screening at age 25 years or older, or were vaccinated at an earlier age and observed as part of screening high-risk populations or through national surveys using self-collected samples. For most studies, individual vaccination status was not known; rather, changes in the prevalence of HPV before and after vaccination were examined. No studies have presented population-based evidence for those vaccinated at age 12 or 13 years where vaccine status is known. With the exception of our own work, no statistically significant evidence of vaccine effectiveness for the grouping of the cross-protective types was found in the aforementioned studies.
Added value of this study
This study is the first to present population-based evidence of the effectiveness of the bivalent HPV vaccine in girls vaccinated routinely at age 12 or 13 years and attending for cervical screening at age 20 years. We have shown that the vaccine-specific types (HPV types 16 and 18) and the cross-protective types (HPV types 31, 33, and 45) have almost disappeared in this population, 7 years following the receipt of vaccine, and present evidence of herd protection for all these types. We also demonstrate significant vaccine effect for the cross-protective types individually.
Implications of all the available evidence
These reductions in the most carcinogenic types of HPV, which are implicated in 90% of cervical cancers in Scotland, will reduce the predictive value of cytology and HPV-based screening strategies, which could affect their cost-effectiveness. Defining optimal screening intervals, age range, test, and triage strategies for vaccinated women should be investigated. Our findings should inform the evaluation of screening programmes in vaccinated populations with high levels of uptake. Additionally, the effectiveness of the vaccine observed, particularly for cross-protective types, might affect the comparative cost-effectiveness of the bivalent, quadrivalent, and nonavalent HPV vaccines and our findings should be incorporated in the baseline assumptions of such evaluative models. If the cross-protection of the bivalent vaccine improves cost-effectiveness then the bivalent vaccine remains a strong candidate for consideration in HPV immunisation programmes.