Randomized Open Trial Comparing 2-Dose Regimens of the Human Papillomavirus 16/18 AS04-Adjuvanted Vaccine in Girls Aged 9-14 Years Versus a 3-Dose Regimen in Women Aged 15-25 Years

Persistent infection with a high-risk human papillomavirus (HPV) type is a prerequisite for cervical cancer [1–3]; therefore, prophylactic HPV vaccination is expected to substantially reduce the burden of this disease, particularly in countries without effective cervical screening programs. The licensed vaccines HPV-16/18 AS04-adjuvanted (Cervarix; GSK Vaccines) and HPV-6/11/16/18 (Gardasil; Merck & Co) were first approved as regimen including 3 doses (3D) with administration over a 6-month period. Reduced dose schedules could make vaccination easier to implement and more affordable, creating the potential for higher vaccination coverage and improved cervical cancer protection [4]. Evaluation of schedules including 2 doses (2D) of the HPV vaccine for girls was first prompted by the observation that 3D schedules elicited HPV-16/18 antibody titers approximately 2-fold higher in girls than in young women [5, 6], the age group in which efficacy was demonstrated in clinical studies [7–13]. A preliminary immunogenicity study evaluating the HPV-16/18 AS04-adjuvanted vaccine showed that 2D given at months 0 and 6 to girls aged 9–14 years was immunologically noninferior 1 month after the last dose to 3D given at months 0, 1, and 6 (M0,1,6) to women aged 15–25 years, and that antibody titers were sustained at high levels for up to 5 years [14–16]. However, the preliminary study was not powered to formally compare immunogenicity between groups beyond 1 month after the last dose. Therefore, the current large phase III study was designed to formally evaluate noninferiority and safety of 2 alternative 2D schedules (months 0 and 6 [M0,6] and months 0 and 12 [M0,12]) in girls aged 9–14 years compared with 3D in women aged 15–25 years over a 3-year period. The study is ongoing, and here we report data up to month 12 or month 13 (depending on the group).