Safety and Immunogenicity of Human Papillomavirus-16/18 AS04-Adjuvanted Vaccine: A Randomized Trial in 10–25-Year-Old HIV-Seronegative African Girls and Young Women

Background. Cervical cancer is a major public health problem for women in sub-Saharan Africa. Availability of a human papillomavirus (HPV) vaccine could have an important public health impact. Methods. In this phase IIIb, double-blind, randomized, placebo-controlled, multicenter trial (NCT00481767), healthy African girls and young women seronegative for human immunodeficiency virus (HIV) were stratified by age (10–14 or 15–25 years) and randomized (2:1) to receive either HPV-16/18 AS04-adjuvanted vaccine (n = 450) or placebo (n = 226) at 0, 1, and 6 months. The primary objective was to evaluate HPV-16/18 antibody responses at month 7. Seropositivity rates and corresponding geometric mean titers (GMTs) were measured by enzyme-linked immunosorbent assay. Results. In the according-to-protocol analysis at month 7, 100% of initially seronegative participants in the vaccine group were seropositive for both anti–HPV-16 and anti–HPV-18 antibodies (n = 130 and n = 128 for 10–14-year-olds, respectively; n = 190 and n = 212 for 15–25-year-olds). GMTs for HPV-16 and HPV-18 were higher in 10–14-year-olds (18 423 [95% confidence interval, 16 185–20 970] and 6487 [5590–7529] enzyme-linked immunosorbent assay units (EU)/mL, respectively) than in 15–25-year-olds (10 683 [9567–11 930] and 3743 [3400–4120] EU/mL, respectively). Seropositivity was maintained at month 12. No participant withdrew owing to adverse events. No vaccine-related serious adverse events were reported. Conclusions. The HPV-16/18 AS04-adjuvanted vaccine was highly immunogenic and had a clinically acceptable safety profile when administered to healthy HIV-seronegative African girls and young women.