title: Overcoming barriers to HPV vaccination: non-inferiority of antibody response to human papillomavirus 16/18 vaccine in adolescents vaccinated with a two-dose vs. a three-dose schedule at 21 months.
abstract: For middle and low-income countries, the cost of HPV vaccines remains challenging. We conducted an open-label nonrandomized clinical trial evaluating immune response to the HPV-16/18 AS04-adjuvanted vaccine administered on a standard (months (M) 0-1-6) versus extended schedule (M 0-6-60) at 7, 21, 60, 72 and 120 months post-vaccination. Participants were females recruited in Morelos, Mexico: 474 girls aged 9-10 years and 500 women aged 18-24 years receiving a standard schedule, and 1026 girls aged 9-10 years receiving an extended schedule (currently the girls in the extended schedule had received only the first 2 doses). This report presents the interim analysis results for non-inferiority between the regimes conducted with the current available data at 21 months after the first dose, with serum antibodies assessed by ELISA. A pre-stated margin of non-inferiority was defined by post-vaccination geometric mean titer (GMT) ratio (upper 95% confidence interval [CI]≤2.0) between the standard and the two-dose schedule in girls at month 21. Immune response to the vaccine was strongest in adolescent girls and in the 3-dose group. Statistical non-inferiority of the two-dose versus three-dose groups was demonstrated. At 21 months, comparing the adolescent 2-dose versus 3-dose groups, the GMT ratio and 95% CI were 1.66 (1.55-1.81) and 1.67 (1.51-1.86) for HPV16 and 18, respectively. The two-dose regimen was non-inferior when compared to the three-dose response in same-age girls and with women aged 18-24 years after 21 months of follow-up. The reduction in the number of doses from the current three-dose schedule may lower overall costs associated with the vaccination and increase accessibility and compliance with the recommended dosing of the HPV vaccine.
authors.affiliation: Centro de Investigación en Salud Poblacional, Instituto Nacional de Salud Pública, Cuernavaca, Morelos, Mexico.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Lazcano-Ponce
authors.affiliation: University of Cambridge, Cambridge, United Kingdom.
authors.forename: Margaret
authors.initials: M
authors.lastname: Stanley
authors.affiliation: National Cancer Institute of Colombia, Bogotá, Colombia.
authors.forename: Nubia
authors.initials: N
authors.lastname: Muñoz
authors.affiliation: Centro de Investigación en Salud Poblacional, Instituto Nacional de Salud Pública, Cuernavaca, Morelos, Mexico.
authors.forename: Leticia
authors.initials: L
authors.lastname: Torres
authors.affiliation: Centro de Investigación en Salud Poblacional, Instituto Nacional de Salud Pública, Cuernavaca, Morelos, Mexico.
authors.forename: Aurelio
authors.initials: A
authors.lastname: Cruz-Valdez
authors.affiliation: Centro de Investigación en Salud Poblacional, Instituto Nacional de Salud Pública, Cuernavaca, Morelos, Mexico; Unidad de Investigación Epidemiológica y en Servicios de Salud, Instituto Mexicano del Seguro Social, Cuernavaca, Morelos, Mexico. Electronic address: jsalme@prodigy.net.mx.
authors.forename: Jorge
authors.initials: J
authors.lastname: Salmerón
authors.affiliation: Centro de Investigación en Salud Poblacional, Instituto Nacional de Salud Pública, Cuernavaca, Morelos, Mexico.
authors.forename: Rosalba
authors.initials: R
authors.lastname: Rojas
authors.affiliation: International Agency for Research on Cancer, Lyon, France.
authors.forename: Rolando
authors.initials: R
authors.lastname: Herrero
authors.affiliation: Centro de Investigación en Salud Poblacional, Instituto Nacional de Salud Pública, Cuernavaca, Morelos, Mexico.
authors.forename: Mauricio
authors.initials: M
authors.lastname: Hernández-Ávila
mesh_terms: D000293:Adolescent; D000914:Antibodies, Viral / Q000097:blood; D002648:Child; D005260:Female; D006297:Health Services Accessibility / Q000191:economics; D006801:Humans; D007115:Immunization Schedule; D008800:Mexico; D030361:Papillomavirus Infections / Q000517:prevention & control*; D053918:Papillomavirus Vaccines / Q000008:administration & dosage* / Q000191:economics; D002583:Uterine Cervical Neoplasms / Q000517:prevention & control / Q000821:virology; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral; D053918:Papillomavirus Vaccines
keywords: HPV-16/18 vaccine; Immunization schedule; Immunogenicity; Non-inferiority trial