Long-Term Follow-Up (LTFU) of Nordic Women Participating in Early Studies of Cervical Cancer Vaccines
In 2002, approximately 5500 young women in the Nordic countries participated in a trial study with the Gardasil vaccine (FUTUREII/V501), making them among the first in the world to receive an HPV vaccine. Similarly, the Gardasil 9 study (V503) started in 2007 with around 4500 participating women in Sweden, Denmark, and Norway. Both vaccines protect against HPV viruses that cause cervical cancer and other HPV-related diseases.
Based on very positive results in these initial studies, the U.S. Food and Drug Administration (FDA) approved the vaccines for commercial use in 2006 (Gardasil) and 2014 (Gardasil-9). Over 100 countries now offer HPV vaccines in their national vaccination programs.
Overview of countries that have introduced HPV vaccine into the national vaccination program. Illustration: www.who.int
Both Gardasil and Gardasil-9 were approved by the FDA on the condition that their safety, effectiveness, and duration would be continuously monitored. Due to the Nordic countries' unique and comprehensive national health registries and cervical cancer screening programs, the FDA identified the Nordic countries as the most suitable place to conduct such follow-up studies. The vaccine manufacturer MSD was mandated to carry out the studies in the Nordic region.
The Cancer Registry is the Nordic Coordinating Unit (NCC) for the studies, conducted in collaboration with the Karolinska Institute (Sweden), the Danish Cancer Society (Kræftens Bekæmpelse), and the Icelandic Cancer Registry (Krabbameinsfélgið).
In both studies, women are passively followed through health registries and cervical cancer screening programs, ensuring that any cases of HPV-related diseases and cellular changes are detected and recorded. All biopsies are reviewed by a Nordic Pathology Panel, consisting of four 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. Additionally, immune responses to the vaccines are examined in blood samples to assess the need for booster shots.
So far, no severe cases of HPV-related cancer have been detected for the HPV types covered by the vaccines. No serious side effects have been observed either. The vaccines maintain a strong and lasting immune response.
Get to know the research group
Get to know the project team working on the evaluation of the effectiveness of the HPV vaccine Gardasil in the "Long Term Follow-Up" (LTFU) projects.
Project leader:
Thea E. Hetland Falkenthal
Project team:
Tina Sture, Tom Erik Nilsen, Elen Johanne Lahlum og Marie Gulla
Funding: Both studies are funded by the vaccine manufacturer MSD Norway.
Project Periods:
LTFU V501: 2009 - 2020 (completed)
LTFU V501 extension: 2021 - 2026
LTFU V503: 2013 - 2025
Privacy:
The projects are conducted in accordance with applicable Norwegian and international privacy regulations and with permission from the Regional Committee for Medical Research Ethics.
Learn more about privacy at the Cancer Registry here
Former project leaders:
Mari Nygård
Bo Terning Hansen
Espen Enerly
Financing
The LTFU studies are commissioned research initiated by Merck & Co, Inc, in response to requirements from the U.S. Food and Drug Administration (FDA).
The LTFU studies are financed by the pharmaceutical manufacturer Merck Sharp & Dohme (MSD) Norway.
Collaborations
The LTFU studies are commissioned research initiated by Merck & Co, Inc, in response to requirements from the U.S. Food and Drug Administration (FDA).
The Cancer Registry is the Nordic Coordinating Unit (NCC) for the studies conducted in collaboration with Kræftens bekempelse (Danish Cancer Society), Karolinska Institutet (Sweden), and Krabbameinsfélgið (Icelandic Cancer Registry)
Publications
2021: Kjaer SK, Nygård M, Sundström K, Munk C, Berger S, Dzabic M, Fridrich KE, Waldstrøm M, Sørbye SW, Bautista O, Group T, Luxembourg A. Long-term effectiveness of the nine-valent human papillomavirus vaccine in Scandinavian women: interim analysis after 8 years of follow-up. Hum Vaccin Immunother. 2021 Apr 3;17(4):943-949. doi: 10.1080/21645515.2020.1839292. Epub 2020 Dec 16. PMID: 33326342; PMCID: PMC8018381.
2020: Kjaer SK, Nygård M, Sundström K, Dillner J, Tryggvadottir L, Munk C, Berger S, Enerly E, Hortlund M, Ágústsson ÁI, Bjelkenkrantz K, Fridrich K, Guðmundsdóttir I, Sørbye SW, Bautista O, Group T, Luxembourg A, Marshall JB, Radley D, Yang YS, Badshah C, Saah A. Final analysis of a 14-year long-term follow-up study of the effectiveness and immunogenicity of the quadrivalent human papillomavirus vaccine in women from four nordic countries. EClinicalMedicine. 2020 Jun 20;23:100401. doi: 10.1016/j.eclinm.2020.100401. PMID: 32637895; PMCID: PMC7329692.
Enerly E, Berger S, Kjær SK, Sundström K, Campbell S, Tryggvadóttir L, Munk C, Hortlund M; Thomas Group. Electronic address: thomas_group@merck.com; Joshi A, Saah AJ, Nygård M. Use of real-world data for HPV vaccine trial follow-up in the Nordic region. Contemp Clin Trials. 2020 May;92:105996. doi: 10.1016/j.cct.2020.105996. Epub 2020 Apr 1. PMID: 32247041.
2018: Kjaer SK, Nygård M, Dillner J, Brooke Marshall J, Radley D, Li M, Munk C, Hansen BT, Sigurdardottir LG, Hortlund M, Tryggvadottir L, Joshi A, Das R, Saah AJ. A 12-Year Follow-up on the Long-Term Effectiveness of the Quadrivalent Human Papillomavirus Vaccine in 4 Nordic Countries. Clin Infect Dis. 2018 Jan 18;66(3):339-345. doi: 10.1093/cid/cix797. PMID: 29029053.
2017: Luxembourg A, Kjaer SK, Nygard M, Ellison MC, Group T, Marshall JB, Radley D, Saah A. Design of a long-term follow-up effectiveness, immunogenicity and safety study of women who received the 9-valent human papillomavirus vaccine. Contemp Clin Trials. 2017 Jan;52:54-61. doi: 10.1016/j.cct.2016.10.006. Epub 2016 Oct 21. PMID: 27777126.
Huh WK, Joura EA, Giuliano AR, Iversen OE, de Andrade RP, Ault KA, Bartholomew D, Cestero RM, Fedrizzi EN, Hirschberg AL, Mayrand MH, Ruiz-Sternberg AM, Stapleton JT, Wiley DJ, Ferenczy A, Kurman R, Ronnett BM, Stoler MH, Cuzick J, Garland SM, Kjaer SK, Bautista OM, Haupt R, Moeller E, Ritter M, Roberts CC, Shields C, Luxembourg A. Final efficacy, immunogenicity, and safety analyses of a nine-valent human papillomavirus vaccine in women aged 16-26 years: a randomised, double-blind trial. Lancet. 2017 Nov 11;390(10108):2143-2159. doi: 10.1016/S0140-6736(17)31821-4. Epub 2017 Sep 5. PMID: 28886907.
2015: Nygård M, Saah A, Munk C, Tryggvadottir L, Enerly E, Hortlund M, Sigurdardottir LG, Vuocolo S, Kjaer SK, Dillner J. Evaluation of the Long-Term Anti-Human Papillomavirus 6 (HPV6), 11, 16, and 18 Immune Responses Generated by the Quadrivalent HPV Vaccine. Clin Vaccine Immunol. 2015 Aug;22(8):943-8. doi: 10.1128/CVI.00133-15. Epub 2015 Jun 17. PMID: 26084514; PMCID: PMC4519713.
2007: FUTURE II Study Group. Quadrivalent vaccine against human papillomavirus to prevent high-grade cervical lesions. N Engl J Med. 2007 May 10;356(19):1915-27. doi: 10.1056/NEJMoa061741. PMID: 17494925.
