Dual staining for p16/Ki‐67 to detect high‐grade cervical lesions: Results from the Screening Triage Ascertaining Intraepithelial Neoplasia by Immunostain Testing study. Issue 2 (24th August 2020)

• Record Type: Journal Article
• Authors: El‐Zein, Mariam; Gotlieb, Walter; Gilbert, Lucy; Hemmings, Robert; Behr, Marcel A.; Franco, Eduardo L.
• Is Part Of: International journal of cancer. Volume 148:Issue 2(2021)
• Page Start: 492
• Page End: 501
• Publication Date: 2020-08-24
• Subjects: cervical cancer screening -- cervical intraepithelial neoplasia -- dual‐stained cytology -- human papillomavirus -- p16/Ki‐67; Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.33250
• Languages: English
• ISSNs: 0020-7136

Abstract

Abstract: We compared clinical performance of p16/Ki‐67 dual‐stained cytology and human papillomavirus (HPV) genotyping, via different algorithms—alone, or in combination with cytology—to identify cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and grade 3 or worse (CIN3+) in women referred to as colposcopy. We included 492 cervical specimens (134 normal, 130 CIN1, 99 CIN2, 121 CIN3, 8 cancers) randomly selected from 1158 specimens with valid conventional cytology, HPV (cobas 4800 HPV test) and biopsy results. Dual‐stained cytology was retrospectively performed (CINtec PLUS assay) on PreservCyt material; slides were read by a cytologist and confirmed by two pathologists, blinded to cytology, biopsy and genotyping results. Sensitivity and specificity (95% confidence intervals in parentheses) of dual‐stained cytology to detect CIN2+ and CIN3+ were compared to other screening tests available for the same women. Positivity rate for dual‐stained cytology increased with histological severity: 30.6% in normal, 41.5% in CIN1, 72.7% in CIN2, 86.8% in CIN3 and 87.5% in cancer. Dual‐stained cytology alone had lower sensitivity than HPV testing for CIN2+ [80.7% (75.0‐85.6) vs 89.9% (85.3‐93.5)] and CIN3+ [86.8% (79.7‐92.1) vs 92.3% (86.2‐96.2)]. However, corresponding specificity values were higher [64.0% (57.9‐69.8) vs 56.1% (49.8‐62.1) for CIN2+; 54.0% (48.7‐59.2) vs 44.4% (39.2‐49.6) for CIN3+]. Combining dual‐stained cytology with an ASC‐US abnormality threshold decreased specificity to 31.4% (25.9‐37.4) for CIN2+ and 24.2% (19.9‐29.0) for CIN3+. The corresponding values considering low squamous intraepithelial lesion threshold values were 42.8% (36.8‐49.0) and 35.0% (30.1‐40.1). Dual‐stained cytology and HPV testing exhibited similar performance, although the former improved the specificity by 7.9% and 9.6% for CIN2+ and CIN3+, respectively. Abstract : What's new? Primary cervical cancer screening with DNA testing for human papillomavirus (HPV) is limited by its lower specificity relative to conventional cytology, thus requiring more efficient triage strategies to avoid excess colposcopy and overtreatment of cervical lesions. This study compared the clinical performance of dual‐stained cytology and HPV genotyping among women referred to colposcopy for abnormal cervical cancer screening results. The data provide further evidence that the combined biomarker p16/Ki‐67, indicative of transforming HPV infections, has a higher specificity for high‐grade cervical lesions than cytology and HPV genotyping. Dual‐stained cytology could support the triaging management of patients with positive high‐risk HPV.