Measuring the effects of the HPV vaccination program

Abstract

Human papillomavirus (HPV) is the most common sexually transmitted infection worldwide. Although most infections clear spontaneously, persistent infection can lead to HPV-related cancers and other HPV-related diseases. HPV vaccination provides primary prevention, while cervical cancer screening provides secondary prevention. This thesis evaluated the impact of HPV vaccination on immunogenicity, high-risk HPV infections, indirect effects, CIN3+ lesions, and cervical cancer. Antibody levels following two doses of the bivalent HPV vaccine declined over time in girls, although HPV16/18 antibody levels remained relatively high for up to 7.5 years. Boys vaccinated at a younger age showed higher HPV16 antibody levels than girls, while no significant sex differences were observed for other HPV types. Vaccine effectiveness was assessed in the HAVANA and HAVANA-2 cohorts. Both two- and three-dose vaccination schedules showed high effectiveness against HPV16/18 infections and significant cross-protection against HPV31 and HPV45. Vaccination also provided indirect protection, with herd immunity effects of approximately 70% for HPV16 and 50% for HPV18. Furthermore, three-dose vaccination was associated with lower viral loads in HPV16/18 infections, suggesting improved clearance. For the first time in the Netherlands, the effectiveness of HPV vaccination on clinical endpoints was evaluated. We observed notable differences in the screening participation rate between vaccine groups. HPV vaccination reduced the risk of invasive cervical cancer by approximately 90% and CIN3+ lesions by approximately 80% among fully vaccinated women, after accounting for differences in screening participation. In 2017, British Columbia switched to the nonavalent HPV vaccine and introduced gender-neutral vaccination. The QUEST-ADVANCE study will evaluate the long-term immunogenicity and effectiveness of one, two, and three doses in girls and boys. Future research should focus on vaccine effectiveness against cervical cancer, changes in HPV type distribution, cross-protection, indirect effects, single-dose vaccination, and improving vaccination and screening participation to reduce health disparities.