Summary
Background
Human papillomavirus (HPV) vaccination programmes were first implemented in several countries worldwide in 2007. We did a systematic review and meta-analysis to assess the population-level consequences and herd effects after female HPV vaccination programmes, to verify whether or not the high efficacy reported in randomised controlled clinical trials are materialising in real-world situations.
Methods
We searched the Medline and Embase databases (between Jan 1, 2007 and Feb 28, 2014) and conference abstracts for time-trend studies that analysed changes, between the pre-vaccination and post-vaccination periods, in the incidence or prevalence of at least one HPV-related endpoint: HPV infection, anogenital warts, and high-grade cervical lesions. We used random-effects models to derive pooled relative risk (RR) estimates. We stratified all analyses by age and sex. We did subgroup analyses by comparing studies according to vaccine type, vaccination coverage, and years since implementation of the vaccination programme. We assessed heterogeneity across studies using I2 and χ2 statistics and we did trends analysis to examine the dose–response association between HPV vaccination coverage and each study effect measure.
Findings
We identified 20 eligible studies, which were all undertaken in nine high-income countries and represent more than 140 million person-years of follow-up. In countries with female vaccination coverage of at least 50%, HPV type 16 and 18 infections decreased significantly between the pre-vaccination and post-vaccination periods by 68% (RR 0·32, 95% CI 0·19–0·52) and anogenital warts decreased significantly by 61% (0·39, 0·22–0·71) in girls 13–19 years of age. Significant reductions were also recorded in HPV types 31, 33, and 45 in this age group of girls (RR 0·72, 95% CI 0·54–0·96), which suggests cross-protection. Additionally, significant reductions in anogenital warts were also reported in boys younger than 20 years of age (0·66 [95% CI 0·47–0·91]) and in women 20–39 years of age (0·68 [95% CI 0·51–0·89]), which suggests herd effects. In countries with female vaccination coverage lower than 50%, significant reductions in HPV types 16 and 18 infection (RR 0·50, 95% CI 0·34–0·74]) and in anogenital warts (0·86 [95% CI 0·79–0·94]) occurred in girls younger than 20 years of age, with no indication of cross-protection or herd effects.
Interpretation
Our results are promising for the long-term population-level effects of HPV vaccination programmes. However, continued monitoring is essential to identify any signals of potential waning efficacy or type-replacement.
Funding
The Canadian Institutes of Health Research.
We confirmed that tubal ligation reduces the risk of epithelial ovarian cancer and particularly endometrioid cancer. To our knowledge, this is the first observational publication to report on salpingectomy and ovarian cancer risk and our promising findings warrant further investigation.
Background
The primary goal of human papillomavirus (HPV) vaccination is to reduce morbidity and mortality from HPV-associated disease, especially cervical cancer. We determined the real-world effectiveness of HPV vaccination against cervical cancer.
Methods
The study included women 17–30 years living in Denmark October 2006–December 2019. From nationwide registries, information on HPV vaccination and cervical cancer diagnoses were retrieved. Incidence rate ratios (IRRs) with 95% confidence intervals (CI) for cervical cancer according to vaccination status were estimated using Poisson regression with HPV vaccination treated as a time-varying variable and stratified by age at vaccination. We adjusted for attained age, education, and ethnicity. To address the effect of prevalent disease, different buffer periods were used, with one-year buffer period as primary analysis.
Results
The cohort comprised 867,689 women. At baseline, 36.3% were vaccinated at ≤ 16 years, and during follow-up, 19.3% and 2.3% were vaccinated at 17–19 and 20–30 years, respectively. For women vaccinated at ≤ 16 or 17–19 years, the IRRs of cervical cancer were 0.14 (95% CI:0. 04–0.53) and 0.32 (95% CI: 0.08–1.28), respectively, compared to unvaccinated women. In women 20–30 years at vaccination, the IR was higher than among unvaccinated women (IRR=1.19, 95% CI: 0.80–1.79), but slightly decreased with increasing buffer period (IRR=0.85 (95% CI: 0.55–1.32) with four-year buffer period).
Conclusion
HPV vaccine effectiveness against cervical cancer at the population-level is high among girls vaccinated before age 20 years. The lack of immediate effect in women vaccinated at age 20–30 years points to the importance of early age at vaccination.
The incidence of GWs decreased substantially among women with high HPV vaccine coverage, pointing to the effect of the national HPV vaccination program.
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