Impact of HPV vaccination on outcome of cervical cytology screening in Denmark-A register-based cohort study

4vHPV vaccination has been tested in randomized controlled trials under almost ideal conditions, and studies of real-life use have compared outcome between vaccinated and unvaccinated women from the same birth cohort and mostly before screening age. Here we present the first-to our knowledge-evaluation of the impact of the 4vHPV vaccination in real life without selection bias in the reported data. The study has been carried out by comparing the results after first cervical screening between an HPV-vaccinated and an unvaccinated birth cohort, consisting of women born in Denmark in 1993 and 1983, respectively. Cytology data covering an 8-year period, from the age of 15 (age of HPV-vaccination) to age 23 (age of invitation to first cervical screening), were retrieved from the Danish National Pathology Register. Abnormal cytology, defined as atypical squamous cell of undetermined significance and worse (ASCUS+) was detected in 9.4% of women born in 1993 as compared with 9.0% of women born in 1983; RR=1.04 (95% CI 0.96-1.12), p=.29. Detection of high-grade squamous intraepithelial lesion (HSIL) was statistically significantly lower in the 1993 than in the 1983 cohort, RR=0.6 (95% CI 0.5-0.7), p<.0001, while the opposite pattern was seen for ASCUS RR=1.4 (95% CI 1.2-1.6), p<.0001. The decrease in HSIL means that more women can be spared referral for colposcopy and biopsy. The increase of ASCUS could be explained by transition from conventional to liquid-based cytology, but this observation requires further monitoring.