The effect of bivalent HPV vaccination against invasive cervical cancer and CIN3+ in the Netherlands: a national linkage study

BackgroundThe protective effect of HPV vaccination against cervical cancer has been demonstrated in registry linkage studies. The start age of screening in those studies was lower than 25 years. We estimated the vaccine effectiveness of bivalent HPV16/18 vaccination against invasive cervical cancer and cervical intraepithelial neoplasia grade 3 (CIN3+) in the Netherlands where routine screening starts at age 30 years. MethodsWe linked the vaccination status of women born in year 1993 who were eligible for HPV vaccination at age 16 years with histopathological results recorded in the nationwide pathology databank (Palga). Cumulative risks of invasive cervical cancer and CIN3+ were estimated for fully vaccinated (3 doses or 2 doses [≥]150 days apart), partially vaccinated, and unvaccinated women. Vaccine effectiveness estimates were adjusted for differences in screening participation between the vaccine groups. FindingsA total of 103,059 women were included, of whom 47,130 were fully vaccinated, 5,098 were partially vaccinated, and 50,831 were unvaccinated. Five (0{middle dot}011%) cancers were observed in fully vaccinated, two (0{middle dot}039%) in partially vaccinated, and 42 (0{middle dot}083%) in unvaccinated women. The vaccine effectiveness in fully vaccinated women was 91{middle dot}5% (95% CI 78{middle dot}9, 96{middle dot}6) against cancer and 81{middle dot}2% (95% CI 78{middle dot}4, 83{middle dot}7) against CIN3+. The vaccine effectiveness in partially vaccinated women was 48{middle dot}1% (95% CI -56{middle dot}8, 82{middle dot}8) against cancer and 58{middle dot}4% (95% CI 45{middle dot}3, 68{middle dot}3) against CIN3+. InterpretationThe high effectiveness of bivalent HPV vaccination against cervical cancer and CIN3+ and the low cancer incidence supports a screening start age of 30 years in vaccinated women. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSWe searched Pubmed and Google Scholar with the search terms ("Cervical Cancer") AND ("HPV" OR "human papillomavirus") AND ("vaccination"). Articles published in English were searched until January 2, 2025. Studies from Sweden, Denmark, and Scotland were identified linking individual vaccination, screening and cancer registry data. The start age of screening in these studies was 23-25 years. They showed a strong effectiveness in preventing cervical cancer following the introduction of bivalent and quadrivalent HPV vaccination. Added value of this studyWe observed a very low absolute incidence of cervical cancer in vaccinated women and a much lower incidence of cervical cancer and CIN3+ in women vaccinated at age 16 compared with unvaccinated women, in a setting where routine screening starts at age 30. By linking the vaccination registry to the nationwide pathology databank, we were able to adjust for screening non-attendance in the incidence of cancer and CIN3+ over a 15 year period. Implications of all the available evidenceOur study supports a start age of screening of at least 30 years in women vaccinated at a young age. Avoiding screening before age 30 in these women is expected to substantially reduce the harms associated with screening and treatment.