HPV Vaccine Schedule in Girls: How Many Doses Do You Need?

A 2-dose quadrivalent human papillomavirus (HPV) vaccine series in girls may be as immunogenic as a 3-dose series in young women, according to the results of a randomized clinical trial conducted in Canada.¹ However, a loss of noninferiority to some genotypes after 2 years requires additional study before a 2-dose schedule can be recommended, the study authors advised.
   
The CDC currently recommends a 3-dose schedule of HPV vaccine administered over 6 months for the prevention of cervical cancer and other cancers caused by infection with HPV genotypes 16 and 18.² The vaccine works best when administered by age 12, ideally before the commencement of any sexual activity with another person; the vaccine also produces higher antibody titers when given at a younger age. However, the cost of this vaccine seems to impede its use, especially in resource-poor countries.
   
To assess whether mean antibody levels to HPV genotypes 6, 11, 16 and 18 among girls receiving 2 doses was noninferior to young women receiving 3 doses, researcher randomized 261 girls aged 9 to 13 years to receive 3 doses of quadrivalent HPV (given at 0, 2, and 6 months) and 259 girls to receive 2 doses (given at 0 and 6 months). In addition, 310 young women aged 16 to 26 years received 3 doses of HPV vaccine at 0, 2, and 6 months. Antibody titers were then measured at 0, 7, 18, 24, and 36 months. Follow-up blood samples were collected from 675 participants (81%).
   
At 7 months, geometric mean titer (GMT) ratios were noninferior for girls receiving 2 doses to women receiving 3 doses and for girls receiving 2 doses to girls receiving 3 doses for all genotypes. The GMT ratios for girls receiving 2 doses to young women receiving 3 doses remained noninferior for all genotypes up to 36 months, the study authors reported. For girls, however, the antibody response in the 2-dose group was inferior to that in the 3-dose group for HPV-18 by 24 months and for HPV-6 by 36 months.
   
Because of the loss of noninferiority over time for some genotypes when just 2 doses of HPV vaccine was given, a reduced-dose schedule cannot be recommended until more information is known about how the number of doses effects the duration of protection.

Pertinent Points:
- Seven months after the first dose of HPV vaccine, antibody levels were comparable between girls and young women regardless of the number of doses they received.
- Compared with girls who received 3 doses of HPV vaccine, girls who received 2 doses had lower antibody titers to HPV-18 by month 24 and HPV-6 by month 36.
- A reduced-dose schedule for HPV vaccine cannot be recommended at this time.
 

References:

1. Dobson SR, McNeil S, Dionne M, et al. Immunogenicity of 2 doses of HPV vaccine in younger adolescents vs 3 doses in young women: a randomized clinical trial. JAMA. 2013;309:1793-1802.
2. Centers for Disease Control and Prevention. HPV vaccine: questions & answers. Available at: http://www.cdc.gov/vaccines/vpd-vac/hpv/vac-faqs.htm. Accessed June 7, 2013.