The effect of HPV vaccination on precancerous lesions and invasive cervical cancer in a low-vaccination-coverage setting in Germany: a retrospective cohort analysis

Background HPV vaccination coverage among 18-year-old women in Germany was 61% in 2024, despite the recommendation for girls since 2007. We assessed the association between HPV vaccination and risk of precancerous lesions and invasive cervical cancer in Bavaria, Germany's largest state. Methods We conducted a retrospective cohort analysis of females born 1990–2005, covering 17 years of follow-up (2008–2024), using health claims and prescription data from the Bavarian Association of Statutory Health Insurance Physicians (KVB). Cumulative incidence of precancerous cervical lesions and invasive cervical cancer was estimated using the Kaplan–Meier method, and risks were estimated using Cox regression models. Analyses accounted for factors such as HPV vaccination status, age at vaccination, pre-vaccination contraceptive prescription, cervical cancer screening participation, and place of residence. Findings Among 669,053 females, 33.76% (225,899/669,053) were fully vaccinated, 13.34% (89,268/669,053) partially vaccinated, and 52.89% (353,886/669,053) unvaccinated. 8965 precancerous lesions and 669 invasive cervical cancers were diagnosed in females aged 19–34 years. By age 34 years, cumulative incidence of precancerous lesions and invasive cervical cancer was 0.025 (95% CI: 0.020, 0.029) and 0.001 (95% CI: 0.001, 0.002) in fully vaccinated cohorts, and 0.041 (95% CI: 0.040, 0.043) and 0.004 (95% CI: 0.003, 0.004) in unvaccinated cohorts, respectively. Adjusted hazard ratios among fully vaccinated females were 0.48 (95% CI: 0.45, 0.52) for precancerous lesions and 0.35 (95% CI: 0.26, 0.47) for invasive cervical cancer. Interpretation HPV vaccination is associated with a lower incidence of precancerous lesions and invasive cervical cancer. This is the first direct evidence of the effectiveness of the HPV vaccine in Germany. Funding No external funding.