Population-level impact, herd immunity, and elimination after human papillomavirus vaccination: a systematic review and meta-analysis of predictions from transmission-dynamic models

Abstract

Background: Modelling studies have been widely used to inform human papillomavirus (HPV) vaccination policy decisions; however, many models exist and it is not known whether they produce consistent predictions of population-level effectiveness and herd effects. We did a systematic review and meta-analysis of model predictions of the long-term population-level effectiveness of vaccination against HPV 16, 18, 6, and 11 infection in women and men, to examine the variability in predicted herd effects, incremental benefit of vaccinating boys, and potential for HPV-vaccine-type elimination.

Methods: We searched MEDLINE and Embase for transmission-dynamic modelling studies published between Jan 1, 2009, and April 28, 2015, that predicted the population-level impact of vaccination on HPV 6, 11, 16, and 18 infections in high-income countries. We contacted authors to determine whether they were willing to produce new predictions for standardised scenarios. Strategies investigated were girls-only vaccination and girls and boys vaccination at age 12 years. Base-case vaccine characteristics were 100% efficacy and lifetime protection. We did sensitivity analyses by varying vaccination coverage, vaccine efficacy, and duration of protection. For all scenarios we pooled model predictions of relative reductions in HPV prevalence (RR_prev) over time after vaccination and summarised results using the median and 10th and 90th percentiles (80% uncertainty intervals [UI]).

Findings: 16 of 19 eligible models from ten high-income countries provided predictions. Under base-case assumptions, 40% vaccination coverage and girls-only vaccination, the RR_prev of HPV 16 among women and men was 0·53 (80% UI 0·46-0·68) and 0·36 (0·28-0·61), respectively, after 70 years. With 80% girls-only vaccination coverage, the RR_prev of HPV 16 among women and men was 0·93 (0·90-1·00) and 0·83 (0·75-1·00), respectively. Vaccinating boys in addition to girls increased the RR_prev of HPV 16 among women and men by 0·18 (0·13-0·32) and 0·35 (0·27-0·39) for 40% coverage, and 0·07 (0·00-0·10) and 0·16 (0·01-0·25) for 80% coverage, respectively. The RR_prev were greater for HPV 6, 11, and 18 than for HPV 16 for all scenarios investigated. Finally at 80% coverage, most models predicted that girls and boys vaccination would eliminate HPV 6, 11, 16, and 18, with a median RR_prev of 1·00 for women and men for all four HPV types. Variability in pooled findings was low, but increased with lower vaccination coverage and shorter vaccine protection (from lifetime to 20 years).

Interpretation: Although HPV models differ in structure, data used for calibration, and settings, our population-level predictions were generally concordant and suggest that strong herd effects are expected from vaccinating girls only, even with coverage as low as 20%. Elimination of HPV 16, 18, 6, and 11 is possible if 80% coverage in girls and boys is reached and if high vaccine efficacy is maintained over time.

Funding: Canadian Institutes of Health Research.

Figure 1:. Model selection

HPV=human papillomavirus. HIC=high-income country. EUROGIN=Eurogin International Multidisciplinary Congress. IPV=International Papillomavirus Conference.

Figure 2:. Population-level impact of HPV vaccination of girls only (A, B) and boys and girls (C, D)

Predicted relative reduction in the prevalence (RR_prev) of HPV 16 among women and men after 70 years of girls-only vaccination, assuming 40% (A) and 80% (B) vaccination coverage; and predicted incremental relative reduction in the prevalence of HPV 16 among women and men after 70 years by vaccinating boys in addition to girls only, assuming 40% (C) and 80% (D) vaccination coverage. The pooled estimates are medians and 80% uncertainty intervals (10% and 90% percentile) of predictions. Models with error bars provided uncertainty intervals (10th and 90th percentile) around their median model predictions. When a model’s results includes a median estimate and uncertainty range, the pooled results used the median value. HPV=human papillomavirus. NA=not available.

Figure 3:. Pooled predictions of the vaccine-type-specific population-level impact of HPV vaccination

Relative reduction of HPV prevalence among women and men after70 years of girls-only vaccination (A), and incremental relative reduction in HPV prevalence among women and men after 70 years by vaccinating boys in addition to girls only (B). Shown here are median (line) and 25th and 75th percentiles (box) and 10th and 90th percentiles (whiskers) of the predictions of the models. HPV 11 results have a different presentation due to the few models that include this outcome. See appendix pp 6–9 for forest plots of model predictions for types HPV 16, 18, 6, and 11; and appendix pp 10–13 for values of pooled estimates and uncertainty intervals. HPV=human papillomavirus.

Figure 4:. Pooled predictions according to vaccination coverage and vaccine type

Relative reduction of HPV prevalence among women and men after girls-only vaccination (A) and after vaccination of boys in addition to girls (B). Shown here are median (line) and 25th and 75th percentiles (box) and 10th and 90th percentiles (whiskers) of the predictions of the models. HPV 11 results have a different presentation due to the limited number of models that include this outcome. See appendix pp 6–9 for forest plots of model predictions for types HPV 16, 18, 6, and 11; and appendix pp 10–13 for values of pooled estimates and uncertainty intervals. HPV=human papillomavirus.