LTFU V501: Extended Long-Term Follow-Up of Women Participating in the Cervical Cancer Vaccine Study (FUTURE II)
This project is an extension of a study that investigated whether the qHPV vaccine can prevent precursors to cervical cancer caused by the virus types included in qHPV. In this extension, we aim to follow the participants for an additional 8 years. The goal of the study is to assess the effectiveness and immunogenicity of the qHPV vaccine over an even longer period. The results of the extension will, among other things, contribute to the assessment of the need for vaccine boosters.
About the project
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Project period: 18.05.2021 - 31.12.2026 (Active)
- Coordinating Institution: Norwegian Institute of Public Health
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Project Manager:
- Thea Eline Hetland Falkenthal, Folkehelseinstituttet
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Project Participants:
- Torbjørn Kjærnli, Medi 3 AS
- Deidre Nsubuga, Gynekologiklinikken
- Kari Anne Trosterud, Kvinnelegen Hedemark
- Ståle Nygård, Kreftregisteret, Folkehelseinstituttet
- Ditte Staldgaard, Kreftregisteret, Folkehelseinstituttet
- Suzanne Campbell, Kreftregisteret, Folkehelseinstituttet
- Kristina Stormo Gjøtterud, Kreftregisteret, Folkehelseinstituttet
- Elen Johanne Lahlum, Kreftregisteret, Folkehelseinstituttet
- Inger Sophie Berger, Kreftregisteret, Folkehelseinstituttet
- Eva Wessel Stratford, Kreftregisteret, Folkehelseinstituttet
Summary
The project is an extension of Protocol V501-015-21, which is a Long-Term Follow-Up (LTFU) study of women who participated in the clinical trial of the quadrivalent HPV vaccine Gardasil (qHPV), which protects against HPV types 6, 11, 16, and 18. Participants first took part in the clinical trial V501-015 (FUTURE II), which investigated whether the vaccine could prevent precancerous lesions of the cervix caused by the HPV types included in qHPV. Participants received either the active vaccine or placebo during a 4-year study period. At the end of the study, participants who had received placebo were offered full vaccination.
The subsequent follow-up study V501-015-21 aimed to assess the effectiveness, immunogenicity, and safety of the qHPV vaccine for at least 10 years after the conclusion of FUTURE II. Participants were followed for approximately 14 years after their first vaccination. In the proposed extension (Protocol V501-015-22), we aim to follow participants for an additional 8 years. The goal of the study is to evaluate the effectiveness and immunogenicity of the qHPV vaccine over an even longer time frame. The results of this extension will contribute to the assessment of whether a booster dose of the vaccine is needed.
Results so far show that Gardasil is a safe vaccine that provides nearly 100% protection against cervical cell changes caused by the HPV types the vaccine is meant to protect against, for up to 14 years.
The current study is an extension of the previous long-term study. Collection of the first round of blood samples, tissue samples, and registry data from participants is underway, and we will provide results from the next analyses for up to 20 and 22 years of follow-up, respectively.
Background
Gardasil is an HPV vaccine targeting HPV types 6, 11, 16, and 18. HPV 6 and 11 cause genital warts, while HPV 16 and 18 can lead to cancer.
As early as 2002, approximately 5500 young women in the Nordic countries participated in the clinical study "FUTURE II," a clinical trial involving the HPV vaccine. In Norway, 1698 women participated. About half of the women received the vaccine, while the other half were given a placebo, a dummy vaccine without active ingredients. The women who received the placebo were offered Gardasil after the study was completed (4 years later).
The study laid the groundwork for the U.S. Food and Drug Administration (FDA) approval of the vaccine for commercial use in 2006. A requirement for the approval was ongoing monitoring of the vaccine's safety, effectiveness, and duration. The Nordic countries were chosen to conduct such a long-term study.
In the initial follow-up study, the women were tracked until 2018 through national health registries and regular blood samples. The results showed that the vaccine has no serious side effects, provides nearly 100% protection against cervical cell changes caused by the HPV types the vaccine targets, and maintains a lasting immune response for up to 14 years.
Current Status
The study has now been extended to ensure follow-up for up to 22 years after the original vaccination and is an extension of the previous long-term follow-up study. The delay was due to the introduction of the General Data Protection Regulation (GDPR) in 2018, which led to changes in the personal data protection law. As a result, new informed consent was obtained for all participants, in addition to measures to ensure compliance with privacy regulations in the transfer of biological material and data between the Nordic countries and the USA.
Only participants who received the vaccine (not the placebo) at the start of the FUTURE II study are included in this round. About 640 women in Norway are currently participating.
In 2022-23 and 2025, blood samples will be collected to measure immune responses and assess the need for a follow-up dose. Simultaneously, registry data from the Cervical Cancer Screening Program, Cancer Registry, Norwegian Patient Registry, and Cause of Death Registry, along with archived tissue samples from study participants who have undergone a histological test since the last analysis, will be collected. In each round, meetings are held with a Nordic Pathology Panel, consisting of 4 expert pathologists who examine the collected tissue samples. The samples are also tested for HPV. The analyses aim to investigate the vaccine's continued protection against HPV-related diseases.
Participant Information
Are you a participant in this study? See Participant information V501
About the project
Funding: The study is funded by the vaccine manufacturer MSD Norway.
Project Period: LTFU V501: 2009 - 2020 (completed), LTFU V501 Extension: 2021 - 2026
REK: The studies have been approved by the Regional Committee for Medical and Health Research Ethics (ref. 2009/1027, ref. 2013/1447)
Scientific Project Titles:
LTFU V501: Long-Term Follow-Up of Women Participating in the Cervical Cancer Vaccine Study (The FUTURE II study/V501 Protocol 015-00) (completed)
LTFU V501 Extension: Extension of Long-Term Follow-Up of Women Participating in the Cervical Cancer Vaccine Study (The FUTURE II study/V501 Protocol 015-00)