Randomized Implementation of a Primary Human Papillomavirus Testing-based Cervical Cancer Screening Protocol for Women 34 to 69 Years in Norway

Background: Cervical cancer screening programs are facing a programmatic shift where screening protocol based on human papillomavirus testing (HPV-Screening protocol) is replacing the liquid-based cytology (LBC-Screening protocol). For safe technol-ogy transfer within the nationwide screening programme in Nor-way, HPV-Screening protocol was implemented randomized to compare the real-world effectiveness of HPV-Screening protocol and LBC-Screening protocol at the first screening round. Methods: Among 302,295 women ages 34 to 69 years scheduled to attend screening from February 2015 to June 2017, 157,447 attended. A total of 77,207 were randomly allocated to the HPV-Screening protocol and 80,240 were allocated to the LBC-Screening protocol. All women were followed up for 18 months. Results: The HPV-Screening protocol resulted in a relative increase of 60% in the detection of cervical intraepithelial neoplasia (CIN) grade 2 or worse [risk ratio (RR) = 1.6, 95% confidence interval (CI) = 1.5-1.7], 40% in CIN grade 3 or worse (RR = 1.4, 95% CI = 1.3-1.6), 40% in cancer (RR = 1.4, 95% CI = 1.0-2.1), and 60% in colposcopy referrals (RR = 1.6, 95% CI = 1.5-1.6) compared with LBC-Screening. The perfor-mance of both protocols was age dependent, being more effective in women ages under 50 years. Conclusions: The HPV-Screening protocol was well accepted by women in Norway and detected more CIN2, CIN3, and cancers compared with the LBC-Screening protocol.Impact: A randomized implementation of the HPV-Screening protocol with real-world assessment enabled a gradual, quality assured, and safe technology transition. HPV-based screening protocol may further be improved by using HPV genotyping and age-specific referral algorithms.

Automated summary

This study compared the effectiveness of HPV-based screening protocol and liquid-based cytology (LBC) screening protocol in detecting cervical intraepithelial neoplasia (CIN) and cancer. The results showed that the HPV-based screening protocol was more effective in detecting CIN2, CIN3, and cancer than the LBC screening protocol. The effectiveness of both protocols varied with age, with better outcomes observed in women under 50 years old.