Population-Level Effects of Human Papillomavirus Vaccination Programs on Infections with Nonvaccine Genotypes

Abstract

We analyzed human papillomavirus (HPV) prevalences during prevaccination and postvaccination periods to consider possible changes in nonvaccine HPV genotypes after introduction of vaccines that confer protection against 2 high-risk types, HPV16 and HPV18. Our meta-analysis included 9 studies with data for 13,886 girls and women ≤19 years of age and 23,340 women 20-24 years of age. We found evidence of cross-protection for HPV31 among the younger age group after vaccine introduction but little evidence for reductions of HPV33 and HPV45. For the group this same age group, we also found slight increases in 2 nonvaccine high-risk HPV types (HPV39 and HPV52) and in 2 possible high-risk types (HPV53 and HPV73). However, results between age groups and vaccines used were inconsistent, and the increases had possible alternative explanations; consequently, these data provided no clear evidence for type replacement. Continued monitoring of these HPV genotypes is important.

Keywords: HPV; HPV vaccination; genotypes; human papillomavirus; nonvaccine types; surveillance; vaccines; viruses.

Figure 1

Flowchart for eligible studies included in systematic review and meta-analysis of changes in prevalences of nonvaccine human papillomavirus (HPV) genotypes after introduction of HPV vaccination. *100% title match, author’s surname and initial, publication year, and periodical; 85% title match, and author surname; ‡includes studies in which the vast majority of the population were unvaccinated. RCT, randomized controlled trials.

Figure 2

Prevalence ratios and 95% CIs for high-risk human papillomavirus (HPV) types (HPV31, HPV33, and HPV45) that had evidence of cross-protection for girls and women <19 years of age and women 20–24 years of age in studies included in a meta-analysis of changes in prevalences of nonvaccine HPV genotypes after introduction of HPV vaccination. A) HPV31; B) HPV33; C) HPV45. Percentages in brackets represent vaccination coverage (>1 dose) for each study and age group. The size of the gray boxes around the plot points indicates the relative weight given to each study in the calculation of the summary estimate. The study by Cameron et al. (25) is omitted from analyses for the younger age group because this study included no data for the group <19 years of age. The study by Cummings et al. (21) is omitted from analyses for women 20–24 years of age because this study included no data for this age group. Pre, prevaccination; post, postvaccination.

Figure 3

Prevalence ratios and 95% CIs for other high-risk human papillomavirus (HPV) types (HPV52 and HPV58) included in the nonavalent vaccine for girls and women <19 years of age and women 20–24 years of age in studies included in a meta-analysis of changes in prevalences of nonvaccine HPV genotypes after introduction of HPV vaccination. A) HPV52; B) HPV58. Percentages in brackets represent vaccination coverage (>1 dose) for each study and age group. The sizes of the gray boxes around the plot points indicates the relative weight given to each study in the calculation of the summary estimate. The study by Cameron et al. (25) is omitted from analyses for the younger age group because this study included no data for persons <19 years of age. The study by Cummings et al. (21) is omitted from analyses for women 20–24 years of age because the study included no data for this age group. Pre, prevaccination; post, postvaccination.