Two Doses of HPV Vaccine in Girls versus 3 Doses in Young Women

Worldwide, cervical cancer is the second most common cause of cancer morbidity and mortality in women. Human papillomavirus (HPV) is a necessary cause for the development of cervical cancer; HPV genotypes 16 and 18 account for approximately 70% of cervical cancer cases.

HPV vaccines need to be administered before persons become sexually active. Canada introduced school-based HPV vaccine programs in 2007, using the quadrivalent HPV vaccine. According to researchers, the global use of HPV vaccines to prevent cervical cancer is impeded by cost and a 2-dose schedule for girls may be possible.

The researchers recently conducted a study to determine whether 2 doses of quadrivalent HPV vaccine given 6 months apart to girls 9 through 13 years of age produced an immune response noninferior to 3 doses in young women 16 through 26 years of age in whom efficacy against disease has been demonstrated. They reported results in JAMA [2013;309(17):1793-1802].

The randomized, phase 3, postlicensure, multicenter, age-stratified, noninferiority immunogenicity study was conducted from August 2007 through February 2011. The study cohort included 830 Canadian females. Follow-up blood samples were provided by 81% of the participants (n=675).

Girls 9 to 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). The third study cohort included young women 16 to 26 years of age who received 3 doses at 0, 2, and 6 months (n=310). Antibody levels were measured at 0, 7, 18, 24, and 36 months.

The primary outcome measure was noninferiority (95% confidence interval [CI], lower bound >.05) of geometric mean titer (GMT) ratios for HPV-16 and HPV-18 for girls (2 doses) compared with young women (3 doses) 1 month after the last dose. Secondary outcomes were noninferiority of GMT ratios of girls receiving 2 versus 3 doses of vaccine and durability of noninferiority to 36 months.

For the primary outcome at 7 months, all but 2 participants (>99%) seroconverted; 1 from the girls cohort receiving 2 doses and 1 from the young women cohort receiving 3 doses did not seroconvert to HPV-16. GMT levels in girls receiving 2 doses were noninferior to young women receiving 3 doses: 2.07 (95% CI, 1.62-2.65) for HPV-16 and 1.76 (95% CI, 1.41-2.19) for HPV-18.

Girls receiving 3 doses had GMT responses 1 month after last vaccination for HPV-16 of 7736 milli-Merck units per mL (mMU/mL) (95% CI, 6651-8999) and HPV-18 of
1730 mMU/mL (95% CI, 1512-1980).

The GMT ratios were noninferior for girls (2 doses) to girls (3 doses): 0.95 (95% CI, 0.73-1.23) for HPV-16 and 0.68 (95% CI, 0.54-0.85) for HPV-18. The GMT ratios for girls (2 doses) to young women (3 doses) remained noninferior after 2 doses versus 3 doses for all 4 vaccine genotypes at month 7, but not for HPV-18 by month 24 or HPV-16 by month 36.

In conclusion, the researchers commented, “Among girls who received 2 doses of HPV vaccine 6 months apart, responses to HPV-16 and HPV-18 one month after last dose were noninferior to those among young women who received 3 doses of the vaccine within 6 months. Because of the loss of noninferiority to some genotypes at 24 to 36 months in girls given 2 doses versus 3 doses, more data on the duration of protection are needed before reduced-dose schedules can be recommended.”