Risk for Cervical Intraepithelial Neoplasia Grade 3 or Higher in Follow-Up of Women With a Negative Cervical Biopsy

Abstract

The Norwegian Cervical Cancer Screening Programme recommends follow-up of histologically confirmed normal/cervical intraepithelial neoplasia (CIN) 1 with combined cytology and human papillomavirus testing within 6 to 12 months. This study examines adherence to guidelines and subsequent risk for CIN 3+ within this subset of women. Women aged 25 to 69 years attending the Norwegian Cervical Cancer Screening Programme in Norway's 2 northernmost counties were included. An exposed cohort with histologically confirmed normal/CIN 1 after an atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesion or atypical squamous cells - cannot exclude high-grade squamous intraepithelial lesion/high-grade squamous intraepithelial lesion enrolment cytology (n = 374) was compared with a nonexposed cohort with a normal enrolment cytology attending primary screening (N = 25,948). Risk calculations were stratified by outcomes of the first follow-up cytology. The study end point was CIN 3+ or censored at 78 months of follow-up. In the exposed cohort, the 42-month cumulative incidence of CIN 3+ was 9.4% (95% CI = 4.1-14.7) for women with an abnormal first follow-up cytology and 1.6% (95% CI = 0.0-3.4) for women with a normal first follow-up cytology versus 0.21% (95% CI = 0.15-0.27) in the nonexposed cohort (p < .01). The CIN 3+ risk was higher in the exposed cohort when the first follow-up cytology was abnormal (hazard ratio = 20.4, 95% CI = 11.2-37.1) compared with normal (hazard ratio = 4.7, 95% CI = 1.9-11.6) with the nonexposed cohort as reference. After a negative cervical biopsy, a normal first follow-up cytology provided a CIN 3+ risk considered acceptable to recommend return to routine screening in 3 years. Cytology and human papillomavirus co-testing in post-colposcopy follow-up of negative biopsies may improve risk stratification.