Study compares effectiveness of two vs. Three doses of HPV vaccine for girls and young women

Simon R. M. Dobson, M.D., of the University of British Columbia, Vancouver, presented the findings of the study at a JAMA media briefing.

"Globally, cervical cancer is the second most common cause of cancer morbidity and mortality in women. Human papillomavirus infection has been identified as a necessary cause for the development of cervical cancer, with HPV genotypes 16 and 18 accounting for approximately 70 percent of cervical cancer cases," according to background information in the article. "Global use of HPV vaccines to prevent cervical cancer is impeded by cost. A 2-dose schedule for girls may be possible."

Dr. Dobson and colleagues conducted a study to determine whether average antibody levels to HPV-16 and HPV-18 among girls receiving 2 doses were noninferior to women receiving 3 doses. The authors also looked at antibody levels to HPV-6 and HPV-11, and compared girls given 2 or 3 doses. The randomized, phase 3, multicenter study included 830 Canadian females from August 2007 through February 2011. Follow-up blood samples were provided by 675 participants (81 percent). Girls (9-13 years of age) were randomized 1:1 to receive 3 doses of quadrivalent HPV vaccine at 0, 2, and 6 months (n=261) or 2 doses at 0 and 6 months (n=259). Young women (16-26 years of age) received 3 doses at 0, 2, and 6 months (n=310). Antibody levels were measured at 0, 7, 18, 24, and 36 months.

The researchers found that the geometric mean titer (GMT) antibody levels in girls receiving 2 doses were noninferior to the respective GMTs in women receiving 3 doses for all 4 genotypes, with GMT ratios of 2.07 for HPV-16 and 1.76 for HPV-18. "Girls given 2 doses vs. 3 doses had a noninferior antibody response for all 4 vaccine genotypes," with GMT ratios of 0.95 for HPV-16 and 0.68 for HPV-18.

"The GMT ratios for girls (2 doses) to women (3 doses) remained noninferior for all genotypes to 36 months. Antibody responses in girls were noninferior after 2 doses vs. 3 doses for all 4 vaccine genotypes at month 7, but not for HPV-18 by month 24 or HPV-6 by month 36."

The authors write that these are the first data, to their knowledge, "on the duration of the immune response of young adolescent girls to a reduced-dose schedule of quadrivalent HPV vaccine out to 3 years." However, "The clinically meaningful difference between the 2- and 3-dose schedules cannot yet be determined."

"Reducing the number of doses affects vaccine and administration costs as well as potentially improving uptake rates. Evidence-based decision making in public health has led to reduced-dose schedules for hepatitis B, pneumococcal, and meningococcal serogroup C vaccine programs. There is a balance to be found between the incremental value of an additional dose on population effectiveness and the opportunity costs of using the resources required for the extra dose in other public health programs. This is especially the case for HPV vaccines at their present cost."