Long-Term Follow-Up Data on Sustained Immunogenicity, Safety for 9-Valent Human Papillomavirus Vaccine
The 9-Valent Human Papillomavirus Vaccine (9vHPV) demonstrated sustained immunogenicity and effectiveness through ∼10 years after the third dose of 9vHPV vaccination of boys and girls aged 9 to 15 years.1 In this Q&A, Elmar A. Joura, MD, answers questions about the long-term follow-up data and the importance of vaccination to prevent against HPV-related cancers and diseases later in life.
Consultant360: Please provide an overview of the long-term follow-up data on sustained immunogenicity and safety for the 9-valent human papillomavirus (9vHPV) vaccine.1
Elmar Joura, MD: The long-term follow-up (LTFU) data on sustained immunogenicity and safety for the 9vHPV vaccine showed no cases of human papillomavirus (HPV)-related high-grade disease, cancers, or genital warts through 10 years post-vaccination for boys and girls aged 9 to 15 years. Data showed sustained HPV antibody responses at ~10 years after the third dose in boys and girls. Most participants remained seropositive for each vaccine-targeted HPV type through the end of the study period. No 9vHPV vaccine-related serious adverse events (SAEs) were reported during the LTFU study.
C360: What are the objectives of the study? And why are they important to the study?
EJ: This LTFU study was an extension of the Phase 3 immunogenicity study for the 9vHPV vaccine in boys and girls aged 9 to 15 years. There were 1272 participants (971 girls, 301 boys) enrolled in the LTFU study. Analysis of the per-protocol population included 872 girls and 262 boys who completed the 9vHPV vaccination series within one year and had not initiated sexual activity before receiving the third dose of 9vHPV. The primary objective of the study was to evaluate anti-HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58 antibody responses through 10 years post-final dose of the 9vHPV vaccine. The secondary objective of the study was 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 and disease.
Safety assessments during the LTFU study included reporting of all vaccine-related SAEs and deaths.
C360: For whom is the 9vHPV vaccine indicated?
In the United States, the 9vHPV vaccine is indicated for use in females 9 through 45 years of age 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.
This vaccine is also indicated for use in males 9 through 45 years of age 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 its 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. The confirmatory trial is ongoing.
The 9vHPV vaccine is contraindicated in individuals with hypersensitivity, including severe allergic reactions to yeast or after a previous dose of the vaccine or HPV quadrivalent types 6, 11, 16, and 18 vaccine, recombinant).
C360: Please explain the dosage and administration guidelines for the 9vHPV vaccine.
EJ: The CDC notes that HPV vaccination may begin at 9 years of age and recommends routine HPV vaccination at 11 to 12 years of age. HPV vaccination is recommended for persons through age 26 years who have not been vaccinated before or have not completed the vaccination series.
9vHPV is a vaccine that is usually given in the arm muscle and may be given as two or three doses.
For persons 9 to 14 years of age, the 9vHPV vaccine can be given using a two-dose or three-dose schedule. For the 2-dose schedule, the second dose should be given 6 to 12 months after the first dose. If the second dose is given less than 5 months after the first dose, a third dose should be given at least 4 months after the second dose. For the three-dose schedule, the second dose should be given 2 months after the first dose, and the third dose should be given 6 months after the first dose.
For persons 15 to 45 years of age, the vaccine is given using a three-dose schedule; the second dose should be given 2 months after the first dose and the third dose should be given 6 months after the first dose.
The appropriate dosing schedule will be determined by a health care professional.
C360: Did any of the findings from the LTFU data surprise you? And how do these findings contribute to existing literature on HPV-related cancers and diseases?
EJ: The results did not surprise me because they fit well into the picture we got from HPV vaccines since their introduction in 2006. The importance of these results is that the girls and boys were vaccinated early, which gives the best prevention of infection and disease. We have now the final proof that the protection is also long-lasting when the vaccine is given at the best age for future protection. This is very reassuring for parents who have already vaccinated their children or plan to do so in the future. I am a father of four children, and I had them vaccinated at 9 to 11 years of age.
C360: What are the overall take-home messages from this study?
EJ: The study results for immunogenicity and reduced incidence of infection and disease for both boys and girls indicate the sustained positive impact the 9vHPV vaccine has on preventing certain HPV-related cancers and diseases.
They highlight the importance and feasibility of HPV vaccination of pre- and young adolescents in the prevention of certain HPV-related cancers and diseases later in life.
C360: What’s next for research on HPV-related cancers and diseases?
EJ: After we have the final proof that invasive cervical cancer is dramatically reduced in women in countries with good vaccine coverage, the future research will also focus on disease in males and especially on HPV-related head and neck cancers, which is on a significant rise in men in the United States and elsewhere. Future research will also focus on recurrent respiratory papillomatosis, which is a rare disease but a significant limitation for the quality of life of those being affected. Trials will also evaluate different intervals between the two doses of HPV vaccination, which provides more flexibility for vaccination programs in various countries worldwide.
C360: Is there anything else you would like to add?
EJ: Get your children vaccinated against HPV. With two doses, you can prevent some cancers and unpleasant diseases in their future lives.
Reference:
1. Restrepo J, Herrera T, Samakoses R, et al. Ten-year follow-up of 9-Valent Human Papillomavirus vaccine: immunogenicity, effectiveness, and safety. Pediatrics. 2023;152(4):e2022060993. doi:10.1542/peds.2022-060993