Risk of high-grade cervical lesions in the second round of primary human papillomavirus testing in CervicalScreen Norway: A population-based cohort study

As many countries are transitioning from cytology to human papillomavirus (HPV) testing as the primary cervical cancer screening test, we evaluated the impact of cumulative HPV screening during the implementation of HPV screening in the Norwegian cervical cancer screening programme (CervicalScreen Norway). Data from the second HPV screening round was compared with data from the first round. The second-round analyses included only women who returned to routine screening 4-6 years following a negative HPV test in the first round. Associations between screening rounds and HPV positivity, cytology results, and follow-up recommendations were estimated by multinomial logistic regression, and relative risks of cervical intraepithelial neoplasia, grade 3 or worse (CIN3+) by Cox regression. There was a 42% lower risk of being HPV positive in the second screening round compared to the first (age-adjusted relative risk ratio (aRRR) 0.58, 95% confidence interval (CI) 0.53 to 0.65), and a 70% lower risk of having high-grade cytology among HPV16 positive women (0.30, 0.12 to 0.78). There was also a 51% reduction in referrals for immediate colposcopy (0.49, 0.39 to 0.62). The overall risk of CIN3+ was 71% lower in the second round compared to the first (age-adjusted hazard ratio [aHR] 0.29, 95%CI 0.21-0.40), and lower among HPV16 and other high-risk HPV positive women, but not among HPV18 positives. No cervical cancers were diagnosed in the second round (mean follow-up 2.4 years). Our findings indicate that HPV test results from previous screening rounds should be considered when designing optimal screening algorithms.