HPV Vaccination Too Soon for 2 Doses? HPV Vaccination: Too Soon for 2 Doses?

Kahn JA, Bernstein DI. — Wed, 01 May 2013 00:00:00 GMT

Cervical cancer is the second most common cancer among women globally, according to age-standardized incidence rates. Approximately 530 000 women are diagnosed with cervical cancer and 275 000 die of the disease every year; 88% of deaths occur in developing regions of the world. Human papillomavirus (HPV) infection is a well-established cause of cervical cancer as well as other anogenital and oropharyngeal cancers; therefore, prophylactic HPV vaccines have the potential to substantially reduce the incidence of cervical cancer and other HPV-associated diseases. Three-dose schedules of the bivalent vaccine (HPV-16 and -18) and the quadrivalent vaccine (HPV-6, -11, -16, and -18) have been shown to be highly efficacious in preventing persistent infection with HPV-16 and -18, which cause approximately 70% of cervical cancers, as well as precancerous lesions associated with these types. The quadrivalent vaccine has also been shown to prevent anogenital warts associated with HPV-6 and -11.

Immunogenicity of 2 Doses of HPV Vaccine in Younger Adolescents vs 3 Doses in Young Women A Randomized Clinical Trial Immunogenicity of HPV Vaccine in Girls vs Women

Dobson SM, McNeil S, Dionne M, et al. — Wed, 01 May 2013 00:00:00 GMT

Importance

Global use of human papillomavirus (HPV) vaccines to prevent cervical cancer is impeded by cost. A 2-dose schedule for girls may be possible.

Objective

To determine whether mean antibody levels to HPV-16 and HPV-18 among girls receiving 2 doses was noninferior to women receiving 3 doses.

Design, Setting, and Patients

Randomized, phase 3, postlicensure, multicenter, age-stratified, noninferiority immunogenicity study of 830 Canadian females from August 2007 through February 2011. Follow-up blood samples were provided by 675 participants (81%).

Intervention

Girls (9-13 years) 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) received 3 doses at 0, 2, and 6 months (n = 310). Antibody levels were measured at 0, 7, 18, 24, and 36 months.

Main Outcomes and Measures

Primary outcome was noninferiority (95% CI, lower bound >0.5) 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 last dose. Secondary outcomes were noninferiority of GMT ratios of girls receiving 2 vs 3 doses of vaccine; and durability of noninferiority to 36 months.

Results

The GMT ratios were noninferior for girls (2 doses) to women (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 (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 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.

Conclusions and Relevance

Among girls who received 2 doses of HPV vaccine 6 months apart, responses to HPV-16 and HPV-18 one month after the 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 vs 3 doses, more data on the duration of protection are needed before reduced-dose schedules can be recommended.

Trial Registration

clinicaltrials.gov Identifier: NCT00501137

AMA Publishing Group: Cervical Cancer Topic Collection

HPV Vaccination Too Soon for 2 Doses? HPV Vaccination: Too Soon for 2 Doses?

Immunogenicity of 2 Doses of HPV Vaccine in Younger Adolescents vs 3 Doses in Young Women A Randomized Clinical Trial Immunogenicity of HPV Vaccine in Girls vs Women