Clinical validation of p16/Ki‐67 dual‐stained cytology triage of HPV‐positive women: Results from the IMPACT trial. Issue 3 (25th September 2021) - Wright, Thomas C.
Abstract: 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 (DS) immunocytochemistry 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 to 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 = 3876) were retested after 1 year. In all, 4927 HPV‐positive women with valid DS results were included in this analysis. DS sensitivity for ≥CIN2 and ≥CIN3 at baseline was 91.2% (95% confidence interval [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 < .0001) or cytology alone (7.5%; 95% CI: 6.7%‐8.4%; P < .0001). DS showed better risk stratification than cytology‐based strategies and provided high reassurance against pre‐cancers 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. Abstract : What's new? Primary screening for human papillomavirus (HPV) requires efficient triage of HPV‐positive women to colposcopy and biopsy. In this prospective observational trial in the United States, with 1‐year longitudinal follow‐up, the authors investigated the performance of p16/Ki‐67 dual‐stain cytology for the triage of women identified as HPV‐positive during primary screening. Compared to HPV16/18 genotyping combined with cytological triage of other HPV genotypes, dual‐stain cytology was significantly more sensitive for predicting risk of cervical intraepithelial neoplasia grade 2/3 or worse. The findings indicate that dual‐stain cytology is effective for triage of HPV‐positive women, either alone or when combined with partial HPV genotyping.