Impact of a Human Papillomavirus Vaccination Program within Organized Cervical Cancer Screening: Cohort Study

Background: We assessed the effectiveness of an HPV (human papillomavirus) vaccination program in lowering cervical abnormality risk, and conferring herd protection. Methods: Retrospective cohort study using linked screening and vaccination administrative health data of the general population of Ancona Province, Italy. We included all female residents born in 1990-1993, eligible for catch-up HPV vaccination up to age 25 years, and adhering to organized screening in 2015-2020 (n = 4,665). Cervical abnormality rates were compared between vaccinated and unvaccinated women, and cohorts with high and low vaccination uptake. Analyses were adjusted for age, country of birth, number of screening tests, laboratory, and municipality average income. Main outcomes were ASC-US+ or LSIL+ Pap smears, and CIN1+ or CIN2+ histology. Results: Mean screening age was 26.6 +/- 1.5 years, and 1,118 screened women (24.0%) were vaccinated (mean vaccination age 19.2 +/- 1.5 years). The diagnosed cervical abnormalities were: 107 LSIL+ (2.3%), 70 CIN1+ (1.5%), and 35 CIN2, - (0.8%). The adjusted odds ratios of LSIL+, CIN1+, and CIN2+ among vaccinated versus unvaccinated women were, respectively, 0.55 [95% confidence interval (CI), 0.33-0.91], 0.43 (95% CI, 0.220.86), and 0.31 (95% CI, 0.11-0.91). Among the unvaccinated, those in the highest-uptake (45.3%) 1993 cohort, versus the last pre-vaccination 1990 cohort, showed AORs of LSIL+ and CIN1+ of 0.23 (95% CI, 0.10-0.50) and 0.22 (95% CI, 0.070.69), respectively. Conclusions: In the first evaluation from central Italy, catch-up HPV vaccination considerably reduced the risk of all cervical abnormalities diagnosed within organized screening, and conferred an elevated degree of herd protection among unvaccinated women. Impact: The high protection conferred by HPV vaccination suggests the need to update cervical screening.