Evaluation of Durability of a Single Dose of the Bivalent HPV Vaccine: The CVT Trial

Abstract

Background: The authors investigated the durability of vaccine efficacy (VE) against human papillomavirus (HPV)16 or 18 infections and antibody response among nonrandomly assigned women who received a single dose of the bivalent HPV vaccine compared with women who received multiple doses and unvaccinated women.

Methods: HPV infections were compared between HPV16 or 18-vaccinated women aged 18 to 25 years who received one (N = 112), two (N = 62), or three (N = 1365) doses, and age- and geography-matched unvaccinated women (N = 1783) in the long-term follow-up of the Costa Rica HPV Vaccine Trial. Cervical HPV infections were measured at two study visits, approximately 9 and 11 years after initial HPV vaccination, using National Cancer Institute next-generation sequencing TypeSeq1 assay. VE and 95% confidence intervals (CIs) were estimated. HPV16 or 18 antibody levels were measured in all one- and two-dose women, and a subset of three-dose women, using a virus-like particle-based enzyme-linked immunosorbent assay (n = 448).

Results: Median follow-up for the HPV-vaccinated group was 11.3 years (interquartile range = 10.9-11.7 years) and did not vary by dose group. VE against prevalent HPV16 or 18 infection was 80.2% (95% CI = 70.7% to 87.0%) among three-dose, 83.8% (95% CI = 19.5% to 99.2%) among two-dose, and 82.1% (95% CI = 40.2% to 97.0%) among single-dose women. HPV16 or 18 antibody levels did not qualitatively decline between years four and 11 regardless of the number of doses given, although one-dose titers continue to be statistically significantly lower compared with two- and three-dose titers.

Conclusion: More than a decade after HPV vaccination, single-dose VE against HPV16 or 18 infection remained high and HPV16 or 18 antibodies remained stable. A single dose of bivalent HPV vaccine may induce sufficiently durable protection that obviates the need for more doses.

Figure 1.

Consolidated standards of reporting trials (CONSORT diagram of women in the nonrandomly assigned extension of the Costa Rica HPV vaccine trial (CVT). This CONSORT diagram shows the women’s progress through the randomly assigned phase of the CVT. The CONSORT then details the nonrandomly assigned extension of CVT, the long-term follow-up study (LTFU), where a new unvaccinated control group (UCG) was recruited to replace the control arm, with similar characteristics to trial participants.

Figure 2.

Human papillomavirus (HPV)16 (graph A) and HPV18 (graph B) antibody levels over time by number of doses received. A linear mixed model using all titer results including replicate testing was used to calculate the Geometric mean titers (GMTs) and 95% confidence intervals (CIs) for single-dose women using continuous time, adjusted by testing batch and using random effects to account for the correlation within a patient and within replicate testing of a visit. For HPV16, the average per-year change in the log titer level for the 221 women with one dose is −0.002 (95% CI = −0.015 to 0.011, P = .72). For HPV18, the average per-year change in the log titer level for the 221 women with one dose is 0.017 (95% CI = 0.005 to 0.029, P = .005).