Immunogenicity of the 9-Valent HPV Vaccine Using 2-Dose Regimens in Girls and Boys vs a 3-Dose Regimen in Women

Abstract

IMPORTANCE Human papillomavirus (HPV) infections cause anogenital cancers and warts. The 9-valent HPV vaccine provides protection against 7 high-risk types of HPV responsible for 90% of cervical cancers and 2 other HPV types accounting for 90% of genital warts.OBJECTIVE To determine whether HPV type-specific antibody responses would be noninferior among girls and boys aged 9 to 14 years after receiving 2 doses of the 9-valent HPV vaccine compared with adolescent girls and young women aged 16 to 26 years receiving 3 doses. DESIGN, SETTING, AND PARTICIPANTS Open-label, noninferiority, immunogenicity trial conducted at 52 ambulatory care sites in 15 countries. The study was initiated on December 16, 2013, with the last participant visit for this report on June 19, 2015. Five cohorts were enrolled: (1) girls aged 9 to 14 years to receive 2 doses 6 months apart (n = 301); (2) boys aged 9 to 14 years to receive 2 doses 6 months apart (n = 301); (3) girls and boys aged 9 to 14 years to receive 2 doses 12 months apart (n = 301); (4) girls aged 9 to 14 years to receive 3 doses over 6 months (n = 301); and (5) a control group of adolescent girls and young women aged 16 to 26 years to receive 3 doses over 6 months (n = 314).INTERVENTIONS Two doses of the 9-valent HPV vaccine administered 6 or 12 months apart or 3 doses administered over 6 months. MAIN OUTCOMES AND MEASURESThe primary end point was prespecified as the antibody response against each HPV type assessed 1 month after the last dose using a competitive immunoassay. Each of the three 2-dose regimens was compared with the standard 3-dose schedule in adolescent girls and young women using a noninferiority margin of 0.67 for the ratio of the antibody geometric mean titers. RESULTSOf the 1518 participants (753 girls [mean age, 11.4 years]; 451 boys [mean age, 11.5 years]; and 314 adolescent girls and young women [mean age, 21.0 years]), 1474 completed the study and data from 1377 were analyzed. At 4 weeks after the last dose, HPV antibody responses in girls and boys given 2 doses were noninferior to HPV antibody responses in adolescent girls and young women given 3 doses (P < .001 for each HPV type). Compared with adolescent girls and young women who received 3 doses over 6 months, the 1-sided 97.5% CIs for the ratio of HPV antibody geometric mean titers at 1 month after the last dose across the 9 HPV subtypes ranged from 1.36 to ϱ to 2.50 to ϱ for girls who received 2 doses 6 months apart; from 1.37 to ϱ to 2.55 to ϱ for boys who received 2 doses 6 months apart; and from 1.61 to ϱ to 5.36 to ϱ for girls and boys who received 2 doses 12 months apart.CONCLUSIONS AND RELEVANCE Among girls and boys aged 9 to 14 years receiving 2-dose regimens of a 9-valent HPV vaccine separated by 6 or 12 months, immunogenicity 4 weeks after the last dose was noninferior to a 3-dose regimen in a cohort of adolescent girls and young women. Further research is needed to assess persistence of antibody responses and effects on clinical outcomes.

Use of a 2-Dose Schedule for Human Papillomavirus Vaccination — Updated Recommendations of the Advisory Committee on Immunization Practices

“…The review focused on this age group given available 2-dose trial data for 9vHPV (4). Immunogenicity outcomes of interest were seroconversion, geometric mean titers (GMTs), or antibody avidity.…”

Seroprevalence of HPV serotypes 6, 11, 16 and 18 in unvaccinated children from Mexico City

“…This first set of values was sent to us by the laboratory once sample processing had been accomplished; at that time, we noticed that these values were higher than the cut-off points cited in other studies published previously (see Appendix 1) [10–19]. Subsequently, and after the laboratory checked the statistical outputs and seropositivity estimates, we were provided with a second set of cut-off points with even higher values that changed the overall picture (the second set of values are: 50, 29, 41 and 59 mMU/ml for HPV6, HPV 11, HPV16 and HPV18, respectively).…”

Human papillomavirus vaccination update: Nonavalent vaccine and the two-dose schedule

“…The nonavalent HPV vaccine has been evaluated in a trial comparing antibody responses in adolescents aged 9-14 years receiving two doses six or 12 months apart with responses seen in women aged 16-26 years receiving three doses. 21 Antibody titres to all nine types were non-inferior (and were, in fact, higher at younger ages).…”