Long-term human papillomavirus vaccination effectiveness and immunity in Rwandan women living with and without HIV: A study protocol

Introduction Prophylactic human papillomavirus (HPV) vaccines have been shown to be highly effective in protecting women against cervical infections, high-grade abnormalities and cancer caused by the targeted HPV types. However, the evidence for their effectiveness in women living with HIV (WLWH) is less clear. Methods WLWH and HIV-negative women who likely did (birth cohorts 1996 and later) and WLWH and HIV(-) negative who likely did not (birth cohorts before 1996) receive HPV vaccination (n=3028; 757 participants for each of the four groups). Between groups, we will compare cervicovaginal, anal and oral prevalent and 6-12 month persistent HPV6/11/16/18 infections as measured using a modified AmpFire HPV genotyping assay that tests for 15 high-risk or intermediate-risk HPV genotypes, HPV6 and HPV11. We will also compare the HPV immune response in HPV-vaccinated WLWH to HPV-vaccinated HIV-negative women using an anti-HPV16 and anti-HPV18 ELISA. Vaccination status will be confirmed through national vaccination records. Analysis We will calculate point prevalence and prevalence of 6-12 month persisting infections by individual HPV-type specific infections and groups of infections for each anatomic site and for each group of women. Results will be stratified by age at vaccination, age at enrolment and the number of doses (3 vs 2) as well as other factors possibly associated with HPV prevalence. Differences in endpoints between groups, overall and between subgroups, will be tested for statistical significance (p<0.05) using Fisher's exact or Pearson χ 2 test. Differences in geometric mean titres and seropositivity will be tested for statistical significance using the Mann-Whitney and Fisher's exact tests, respectively. Ethics and dissemination The study was approved by the Albert Einstein College of Medicine Institutional Review Board and the Rwanda National Ethics Committee. Results will be disseminated through publication in peer-reviewed journals.