New 10-year follow-up data were published by Restrepo et al in Pediatrics on girls and boys who received a three-dose regimen of the 9-valent human papillomavirus (HPV) vaccine between the ages of 9 and 15. The long-term follow-up study was conducted from 2009 through 2021 across 13 countries and 5 continents.
More About the Study
The phase III immunogenicity study for the 9-valent HPV vaccine in boys and girls aged 9 to 15 years was extended to a long-term follow-up study to assess immunogenicity through 10 years after the last 9-valent HPV vaccine dose. The long-term follow-up study was conducted at 40 sites across 13 countries: Belgium, Brazil, Colombia, Costa Rica, Peru, Poland, South Africa, South Korea, Spain, Sweden, Taiwan, Thailand, and the United States. There were 1,272 participants—971 girls and 301 boys). Analysis of the per-protocol population included 872 girls and 262 boys who completed the 9-valent HPV vaccination series within 1 year, were seronegative to the relevant HPV type at initiation of the vaccination series, and had not initiated sexual activity prior to receiving the third dose of the vaccine.
The primary objective of the long-term follow-up study was to evaluate anti-HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58 antibody responses through 10 years post the third dose of the 9-valent HPV vaccine. Secondary objectives were to estimate the long-term incidence of the composite endpoint of HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58-related persistent infection (≥ 6 months duration ±1 month visit window) and disease. Safety assessments during the long-term follow-up study included reporting of all deaths and vaccine-related serious adverse events.
Immunogenicity and Incidence of Persistent Infection and Disease
As part of the primary objective of immunogenicity, data showed sustained HPV-antibody responses at 10 years after the third dose in boys and girls. Across 9-valent HPV vaccine–targeted HPV types, antibody assessments evaluated through geometric mean titers peaked at month 7 and decreased thereafter through 126 months. The majority of study participants remained seropositive at the end of the study period; 99.6% to 100% of study participants were seropositive for the targeted HPV types at month 7 based on HPV-9 competitive Luminex immunoassay, and 81.3% to 97.7% remained seropositive at month 126 depending on the HPV type. Based on the HPV-9 immunoglobulin G Luminex immunoassay, 94.9% to 100% of participants were seropositive at month 126.
In accordance with the study’s secondary objective, incidence of persistent infection and disease related to vaccine-targeted HPV types was assessed in the per-protocol population in both female and male participants. Female participants were followed up to 11 years after the third dose (median = 10 years), and male participants were followed up to 10.6 years after the third dose (median = 9.9 years).
Among girls, there were no cases of vaccine-targeted HPV type high-grade disease (cervical intraepithelial neoplasia [CIN] 2/3, adenocarcinoma in situ, vulval intraepithelial neoplasia, or vaginal intraepithelial neoplasia) certain cancers (cervical, vulvar, and vaginal), or external genital warts observed. One case of CIN1 that tested positive for HPV 16, 39, and 59 was observed at month 84. Cervical cytology results were negative at subsequent visits.
In boys, there were no cases of vaccine-targeted HPV type disease (penile intraepithelial neoplasia, certain studied cancers (penile, perineal, and perianal) or external genital warts observed.
No 9-valent HPV vaccine–related serious adverse events or deaths were reported throughout the long-term follow-up study. The most common reasons for discontinuations from the study were due to participant withdrawal or loss to follow-up.
Current 9-Valent HPV Vaccine Indications
In the United States, the 9-valent HPV vaccine is indicated for use in females aged 9 to 45 years for the prevention of cervical, vulvar, vaginal, anal, oropharyngeal, and other head and neck cancers caused by HPV types 16, 18, 31, 33, 45, 52, and 58; cervical, vulvar, vaginal, and anal precancerous or dysplastic lesions caused by HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58; and genital warts caused by HPV types 6 and 11. The 9-valent HPV vaccine is also indicated for use in males aged 9 to 45 years for the prevention of anal, oropharyngeal, and other head and neck cancers caused by HPV types 16, 18, 31, 33, 45, 52, and 58; anal precancerous or dysplastic lesions caused by HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58; and genital warts caused by HPV types 6 and 11. The oropharyngeal and head and neck cancer indication is approved under accelerated approval based on effectiveness in preventing HPV-related anogenital disease; continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial, which is ongoing.
Disclosure: For full disclosures of the study authors, visit publications.aap.org/pediatrics.
