The human papillomavirus 16/18 vaccine showed efficacy, sustained immunogenicity, and continued safety for up to 6.4 years in a combination of initial and follow-up placebo-controlled studies involving more than 1,000 women aged 15-26 years.
The human papillomavirus (HPV) vaccine, Cervarix, is now licensed in the United States, Europe, and elsewhere around the world. It contains the HPV types 16 and 18 adjuvanted with ASO4, comprising aluminum salt and an immunostimulatory molecule that has been shown to produce higher antibody titers that are sustained over a longer period of time, compared with the same antigens adjuvanted with aluminum salts alone, according to the GSK Vaccine HPV-007 Study Group, led by Dr. Barbara Romanowski (Lancet 2009 Dec. 3 [doi:10.1016/S0140-6736(09)61567-1]).
Of 1,113 women included in the initial three-country, 27-site study, a total of 700 completed the follow-up study. The total vaccinated cohort included 560 women in the vaccine group and 553 in the placebo group, while the according-to-protocol (ATP) efficacy cohort included 465 in the vaccine group and 454 in the placebo group. At baseline, all had normal cervical cytology and were negative for both HPV-16 and −18.
The mean follow-up period from the start of the initial study was 5.9 years, with a maximum duration of 6.4 years. The study population was racially diverse, with a mean age of 20 years (range 15-26 years) at entry to the initial study and 23 years at the beginning of the follow-up study.
At 6.4 years, vaccine efficacy against incident HPV-16 or HPV-18 infection in the ATP analysis was 95.3%, and long-term efficacy against persistent infection was 100% at both 6 and 12 months. In the total vaccinated cohort analysis, protection against cervical intraepithelial neoplasia grade 1 or higher associated with either vaccine HPV type was 100%. For the nonvaccine types HPV-31 and −45, vaccine efficacy against incident infection was 59.8% and 77.7%, while overall efficacy against any cervical intraepithelial neoplasia grade 2 or higher independent of HPV type was 71.9%, said Dr. Romanowski of the University of Alberta, Edmonton, and her associates.
Almost all vaccine recipients (99%) remained seropositive for anti–HPV-16 and anti–HPV-18 total IgG antibodies. After a peak response at 7 months, geometric mean titers for both antibodies reached a plateau between 18 and 24 months post vaccination, and remained stable thereafter. During months 63-76, antibody concentrations against HPV-16 and HPV-18 were at least 13-fold and 12-fold higher than were concentrations recorded following clearance of a natural infection in a previous study (Lancet 2007;369:2161-70).
Safety profiles of the HPV-16/18 vaccine and placebo were similar, with approximately one-third of each group reporting any adverse event, 10% or fewer reporting a serious adverse event, and less than 10% reporting new-onset chronic diseases. None of the serious adverse events was judged to be related to the vaccine, and there were no deaths.
In an accompanying editorial, Dr. Gary M. Clifford wrote that the data showing no evidence of further decline from 3 to 6 years are “perhaps the most interesting” because they suggest that mean antibody concentrations should remain well above those associated with natural infection long into the future.
The target age of vaccination is a balance between “being early enough to catch girls before sexual debut, but late enough to provide an as yet unknown duration of immunity that protects during as many subsequent years of sexual activity as possible,” wrote Dr. Clifford of the International Agency for Research on Cancer, Lyon, France (Lancet 2009 Dec. 3 [doi:10.1016/S0140-6736(09)61789-X]).
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Major Finding: At 6.4 years, vaccine efficacy against incident HPV infection was 95% in the according-to-protocol cohort.
Source of Data: A three-country, 27-site study of 1,113 women aged 15-26 years.
Disclosures: The study, led by Dr. Romanowski, was funded by GlaxoSmithKline (GSK) Biologicals, manufacturer of Cervarix. Dr. Clifford declared that he had no conflicts of interest.