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 = 0.29. 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 <0.0001, while the opposite pattern was seen for ASCUS RR = 1.4 (95% CI 1.2-1.6), p <0.0001. 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. This article is protected by copyright. All rights reserved.