Giving the quadrivalent HPV vaccine on two of three alternative dosing schedules that are better suited to resource-poor regions than is the standard schedule was found to be "noninferior" among young adolescent girls in an underserved region in Vietnam, according to a report in the April 13 issue of JAMA.
In this clinical trial involving 903 girls aged 11-13 years, the quadrivalent HPV vaccine proved to be noninferior when given at 0, 3, and 9 months and at 0, 6, and 12 months, compared with the standard 0-, 2-, and 6-month dosing schedule. When given on the third alternative dosing schedule at 0, 12, and 24 months, the vaccine did not meet the strict study criteria for noninferiority but was still found to be "highly immunogenic," said Dr. Kathleen M. Neuzil of PATH, an international nonprofit organization that addresses global health problems and is headquartered in Seattle.
"The similarity of the immunogenicity and reactogenicity profiles of the HPV vaccine reported from this predominantly ethnic minority population in a low-resource area of Vietnam ... is reassuring, and supports more widespread introduction of the vaccine," Dr. Neuzil and her colleagues reported. "The option of delivering HPV vaccine on flexible schedules will allow countries to minimize costs and maximize feasibility according to local vaccination practices" (JAMA 2011;305:1424-31).
Dr. Neuzil and her colleagues performed the open-label, randomized trial at 21 schools in predominantly rural northwestern Vietnam in 2007-2010.
The first alternative dosing schedule they assessed – at 0, 3, and 9 months – would be less restrictive than would the standard schedule because it would fit into the region’s existing schedule for medical outreach services to isolated areas. The second alternative schedule – at 0, 6, and 12 months – would be more useful because it could coincide with the semiannual "health days" often held in resource-poor nations. The third alternative schedule – at 0, 12, and 24 months – could be incorporated into other countries’ annual health programs, particularly those given at schools, the researchers noted.
The primary end point was immunogenicity to HPV-16 and HPV-18 at 1 month after receipt of the final dose. According to the strict study definitions, the first two alternative dosing schedules met noninferiority criteria for HPV-16 and HPV-18, but the third (annual) schedule met the criteria only for HPV-18.
A secondary outcome was immunogenicity to the other two virus types, HPV-6 and HPV-11, which are covered by the quadrivalent vaccine. Again the first two alternative dosing schedules met the strict noninferiority criteria for HPV-6 and HPV-11, but the annual schedule met the criteria only for HPV-11.
Although the antibody concentrations against HPV-16 and HPV-6 were lower with the annual schedule than with the other dosing schedules assessed in this study, they still were higher than those that have been reported among women aged 16-26 years. "It is difficult to know if these lower anti-HPV [titers] will translate to significantly different efficacies against important clinical outcomes, such as high-grade precancerous lesions," Dr. Neuzil and her associates noted.
Extended follow-up is underway to answer this question and to determine whether longer-term antibody responses are affected by dosing schedule, they added.
The vaccine was well tolerated, and the proportion of subjects with adverse events was comparable across all the study groups. No serious adverse events were reported.
This study was funded by the Bill and Melinda Gates Foundation. Merck & Co. provided the vaccine and the immunogenicity testing at no charge. The researchers reported no relevant financial disclosures.