High risk human papillomavirus versus cytological screening over two rounds in Finnish screening programme for cervical cancer: population based cohort study.

Objective: To compare routine high risk human papillomavirus (hrHPV) screening with cytological screening in two screening rounds in a well established, routine screening programme for cervical cancer. Design: Population based cohort study. Setting: Finland's Mass Screening Registry, 2012-22, with diagnostic follow-up examinations until October 2024. Participants: 1 180 491 women participating at least once in cytological test (PAP smear) or hrHPV based cervical cancer screening between 2012 and 2022. Main outcome measures: Numbers and proportions of attendees, positive routine test results, follow-up screening referrals, colposcopy referrals, and incidence of cervical intraepithelial neoplasia ≥grade 2 (CIN2+) in the first and second hrHPV and cytological screening rounds. Results adjusted for age, year, region, and education. Results: Data for 1 574 688 full screening rounds were analysed. The overall referral rate for colposcopy was 3.37% (n=12 273) in the hrHPV group and 0.98% (n=11 895) in the cytology group, with an adjusted risk ratio of 2.97 (95% confidence interval (CI) 2.87 to 3.07). The overall rate for detection of CIN2+ was 0.92% in the hrHPV group and 0.35% in the cytology group, with an adjusted risk ratio of 2.17 (2.04 to 2.31). For the second hrHPV screening round compared with the first screening round, the adjusted risk ratio was 0.77 (0.71 to 0.84) for referral for colposcopy and 0.57 (0.46 to 0.72) for detection of CIN2+. Actual rates for referral for colposcopy were 3.54% (n=11 709) in the first hrHPV screening round and 2.42% (n=564) in the second screening round. The rate for detection of CIN2+ for hrHPV screening was 0.98% (n=3 248) in the first hrHPV screening round and 0.38% (n=88) in the second screening round. In cytological screening, no observed reduction was seen in either the referral rate or CIN2+ findings. After a negative hrHPV test in the first screening round, CIN2+ was detected in only 0.2% of women (n=44/314 286) in the second screening round. Conclusions: Within a well established, population based national screening programme, the results of the study indicated that hrHPV screening with a five year interval was effective and safe. hrHPV screening identified precancerous lesions earlier than cytological screening. The incidence of CIN2+ was low in the second screening round in women with a negative hrHPV test result in the initial round and in those aged ≥50 years, and hence a longer screening interval for specific subgroups should be considered.