Long-Term Follow-Up (LTFU) of Nordic Women Participating in Early Studies of Cervical Cancer Vaccines

The Long-Term Follow-Up (LTFU) studies investigate the safety, effectiveness, and duration of the HPV vaccines Gardasil and Gardasil-9.

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.