Impact of Human Papillomavirus Vaccination, Rwanda and Bhutan

Abstract

Rwanda and Bhutan, 2 low- and middle-income countries, implemented primarily school-based national human papillomavirus (HPV) vaccination in 2011 (Rwanda) and 2010 (Bhutan). We estimated vaccination effectiveness through urine-based HPV prevalence surveys in schools in 2013-2014 and 2017. In Rwanda, 912 participants from baseline surveys and 1,087 from repeat surveys were included, and in Bhutan, 973 participants from baseline surveys and 909 from repeat surveys were included. The overall effectiveness against vaccine-targeted HPV types (i.e., HPV-6/11/16/18) was 78% (95% CI 51%-90%) in Rwanda, and 88% (6%-99%) in Bhutan and against other α-9 types was 58% (21-78) in Rwanda and 63% (27-82) in Bhutan. No effect against other HPV types was detectable. Prevalence of vaccine-targeted HPV types decreased significantly, as well as that of other α-9 types, suggesting cross-protection. These findings provide direct evidence from low- and middle-income countries of the marked effectiveness of high-coverage school-based, national HPV vaccination programs.

Keywords: Bhutan; Rwanda; disease control; epidemiologic monitoring; human papillomavirus recombinant vaccine quadrivalent; low-income population; papillomavirus infections; papillomavirus vaccines; type 11; type 16; type 18; type 6; vaccine-preventable diseases; vaccines; viruses.

Figure 1

Timing of school-based human papillomavirus vaccination program and surveys in Rwanda (A) and Bhutan (B). Short dashed line represents routine vaccination. Long dashed line represents catch-up vaccination.

Figure 2

Analytical framework used to assess the impact of human papillomavirus (HPV) vaccination in Rwanda and Bhutan. A) Vaccinated participants in the baseline survey. B) Unvaccinated participants in the baseline survey. C) Vaccinated participants in the repeat survey. D) Unvaccinated participants in the repeat survey. Vaccine effectiveness (VE) was calculated as VE = (1 – PR)%, where PR is a prevalence ratio (PR). Each type of VE is defined according to specific criteria for selecting comparison groups on the basis of reported vaccination status. Overall effectiveness estimates, providing a measure of HPV prevalence reduction over time attributable to vaccination irrespective of the reported vaccination status of each person, were obtained by comparing the type-specific HPV prevalence in all women, unvaccinated and vaccinated, recruited in the baseline and repeat surveys. PR (C and D) / PR (A and B) = overall PR. Restricted effectiveness estimates, providing an approximate estimate of the impact of HPV vaccination versus an entirely unvaccinated population, were obtained by comparing the type-specific HPV prevalence in unvaccinated women in the baseline and all women in repeat surveys. PR (C and D) / PR (B) = restricted PR. Total effectiveness estimates, providing a vaccine efficacy estimate (similar to measures from clinical trials) from real-life settings, were obtained by comparing the type-specific HPV prevalence in unvaccinated women in the baseline and vaccinated women in repeat surveys. PR (C) / PR (B) = total PR, where PR (•) is the type-specific HPV prevalence in each participant group.

Figure 3

Overall crude human papillomavirus prevalence by general primer GP5+/6+-mediated PCR in baseline and repeat surveys in Rwanda (A) and Bhutan (B), with corresponding 95% CIs. Vaccine-targeted types (HPV-6, -11, -16, -18); other α-9 types (HPV-31, -33, -35, -52, -58); other α-7 types (HPV-39, -45, -59, -68); non–α 7/9 types (HPV-26, -51, -53, -56, -66, -70, -73, -82).