Impact of HIV on Women Internationally1

particles (VLPs). Species-specific VLP vaccines provide protection against infection and disease. Protection was associated with the development of neutralizing antibodies. Serum from vaccinated animals conferred protection to unvaccinated animals. The HPV-6, HPV-11, HPV-16, and HPV-18 L1 VLP vaccine is manufactured in Saccharomyces cerevisiae (yeast), and yeast-derived vaccines have been given to millions of children and adults. The vaccine includes amorphous aluminum hydroxyphosphate sulfate adjuvant and is given in a 0-, 2-, 6-month dosing scheme. Phase I trials (300 participants) were performed to establish immunogenicity and tolerability of a range of doses of monovalent HPV L1 vaccines. Phase II trials (3,500 participants) were performed to establish the immunogenicity and tolerability of a range of HPV L1 VLP vaccine dose formulations and provide preliminary proof of concept. Phase III trials (20,000 participants) will determine the efficacy of the HPV L1 VLP vaccine by using prevention of type-related CIN I, genital warts, and CIN II/III as the endpoints. The results of the phase II trial of the HPV-16 VLP vaccine have been recently published (1). The primary endpoint of this trial in 2,392 young women was persistent HPV-16 infection (detection in consecutive visits) and HPV-16-related CIN. In 16to 23-year-old women who were HPV-16-naïve at baseline, the vaccine was 100% effective; HPV-16 and CIN were detected in 41 unvaccinated (placebo) women and in no vaccinated women. The vaccine was generally well tolerated, and no serious vaccine-related adverse events were seen. The phase III efficacy trial addressing women 16–-23 years is underway. Approximately 25,000 women in 33 countries and 100 sites have been enrolled. The evaluation includes Pap testing and HPV polymerase chain reaction at defined intervals. An adolescent program (for girls 9-15 years of age) is ongoing to demonstrate vaccine immunogenicity and tolerability in boys and girls. In addition, a study with Nordic Cancer Registries is planned for longterm (>10 years) follow-up postlicensure to determine duration of efficacy, long-term safety, and replacement of vaccine types with other HPVs. Phase III programs will definitively evaluate clinical and public health impact of the HPV vaccine in adolescents and adult women.