A candidate vaccine against human papillomavirus (HPV) produced by GlaxoSmithKline, AS04 (Cervarix), provides extended protection against HPV 16 and 18 not only for young women but also for women up to the age of 55
ASCOA candidate vaccine against human papillomavirus (HPV) produced by GlaxoSmithKline, AS04 (Cervarix), provides extended protection against HPV 16 and 18 not only for young women but also for women up to the age of 55, according to findings of a phase III study reported at the 43rd Annual Meeting of the American Society of Clinical Oncology (abstract 3007).
Principal investigator Tino F. Schwarz, MD, of Stiftung Juliusspital, Wuerzburg, Germany, commented that protecting older women is very important. "There is risk for HPV infection [and cervical cancer] at all ages," he said. "The ability to clear HPV is less in older than in younger women, and the risk of persistent infection increases with age."
The primary trial included 668 women aged 15 to 55 from Germany and Poland who were DNA negative and seronegative for HPV. Patients received one dose of the GSK cervical candidate vaccine at three time points: baseline, 1 month, and 6 months. Evaluation at 12 months showed the vaccine was highly immunogenic and well tolerated. The study was extended up to 48 months with 517 women participating, stratified by age (15-25, 26-35, 36-45, and 46-55).
At 18 months after the first dose, 100% of women in the study had antibodies against the two HPV strains most associated with cervical cancer, HPV 16 and 18, Dr. Schwarz reported.
For women in the three oldest age groups, the antibody levels for HPV 16 and HPV 18 were virtually identical to those of the youngest group. Safety outcomes were also comparable in all age groups, he said.
Further, these antibody levels corresponded to those seen at the same time point in women aged 15 to 25 in a separate efficacy study of the vaccine. In that study, these antibody levels provided 100% sustained protection against HPV 16 and 18 infection for up to 5.5 years (Harper et al: Lancet 367:1247-1255, 2006).
Peaks and Plateaus
For the women in the efficacy study, antibody concentrations of HPV 16 peaked at 7 months and began to plateau at 18 months at approximately 1,000 EU/mL, Dr. Schwarz reported. "The curves for the older subjects follow the same pattern. There is no reason they will not follow the same line and plateau out to 5 years," he said. Similar curves were seen for HPV 18.
The HPV 16 antibody concentrations for all age groups were about 10-fold higher (9-fold for HPV 18) at 18 months than antibody concentrations that result from natural exposure. "Natural infection does not translate into immunity," Dr. Schwarz noted.
The study also assessed for the presence of cervical mucosal antibodies against HPV 16 and 18 elicited by the vaccine, and found a very strong correlation between antibody levels in the serum and those in vaginal secretions. "Cervical mucosal antibodies should be an important aspect of protection," Dr. Schwarz said. "This indicates that the higher the antibody concentration in the serum, the more likely the antibodies will arrive at the genital mucosa, where they are needed."
Vaccinate Before Exposure
At entry, 19% of subjects already had antibodies to HPV 16, especially those in the older age groups. About 10% had antibodies to both HPV 16 and 18.
In a discussion of the paper, Mary L. Disis, MD, associate professor of medicine, University of Washington, Seattle, noted that when a woman is both DNA negative and seronegative for HPV, the vaccine is 100% effective. If a woman is DNA positive and seronegative, the vaccine is about 33% protective.
But if a woman is both DNA positive and seropositive, the vaccine will not be protective. Therefore, Dr. Disis emphasized, vaccination before HPV exposure is important.