LAUSR

Triage strategies are needed for primary human papillomavirus (HPV)-based cervical cancer screening to identify women requiring colposcopy/biopsy. We assessed the performance of p16/Ki-67 dual-stained immunocytochemistry (DS) to triage HPV-positive women and compared it to cytology, with or without HPV16/18 genotyping. A prospective observational screening study enrolled 35,263 women aged 25-65 years at 32 U.S. sites. Cervical samples had HPV and cytology testing, with colposcopy/biopsy for women with positive tests. Women without cervical intraepithelial neoplasia grade 2 or worse (≥CIN2) at baseline (n=3,876) were retested after 1 year. 4,927 HPV-positive women with valid DS results were included in this analysis. DS sensitivity for ≥CIN2 and ≥CIN3 at baseline was 91.2% (95% CI: 86.8%-94.2%) and 91.9% (95% CI: 86.1%-95.4%), respectively, in HPV16/18-positive women, and 83.0% (95% CI: 78.4%-86.8%) and 86.0% (95% CI: 77.5%-91.6%) in women with 12 "other" genotypes. Using DS alone to triage HPV-positive women showed significantly higher sensitivity and specificity than HPV16/18 genotyping with cytology triage of 12 "other" genotypes, and substantially higher sensitivity but lower specificity than using cytology alone. The risk of ≥CIN2 was significantly lower in HPV-positive, DS-negative women (3.6%; 95% CI: 2.9%-4.4%), compared to triage-negative women using HPV16/18 genotyping with cytology for 12 "other" genotypes (7.4%; 95% CI: 6.4%-8.5%; p<0.0001), or cytology alone (7.5%; 95% CI: 6.7%-8.4%; p<0.0001). DS showed better risk stratification than cytology-based strategies and provided high reassurance against precancers both at baseline and at 1-year follow-up, irrespective of the HPV genotype. DS allows for the safe triage of primary screening HPV-positive women. This article is protected by copyright. All rights reserved.