TY - JOUR T1 - Three-tiered score for Ki-67 and p16<sup>ink4a</sup> improves accuracy and reproducibility of grading CIN lesions JF - Journal of Clinical Pathology JO - J Clin Pathol SP - 981 LP - 988 DO - 10.1136/jclinpath-2018-205271 VL - 71 IS - 11 AU - Marjolein van Zummeren AU - Annemiek Leeman AU - Wieke W Kremer AU - Maaike C G Bleeker AU - David Jenkins AU - Miekel van de Sandt AU - Daniëlle A M Heideman AU - Renske Steenbergen AU - Peter J F Snijders AU - Wim G V Quint AU - Johannes Berkhof AU - Chris J L M Meijer Y1 - 2018/11/01 UR - http://jcp.bmj.com/content/71/11/981.abstract N2 - Aims To investigate the accuracy and reproducibility of a scoring system for cervical intraepithelial neoplasia (CIN1–3) based on immunohistochemical (IHC) biomarkers Ki-67 and p16ink4a.Methods 115 cervical tissue specimens were reviewed by three expert gynaecopathologists and graded according to three strategies: (1) CIN grade based on H&amp;E staining only; (2) immunoscore based on the cumulative score of Ki-67 and p16ink4a only (0–6); and (3) CIN grade based on H&amp;E supported by non-objectified IHC 2 weeks after scoring 1 and 2. The majority consensus diagnosis of the CIN grade based on H&amp;E supported by IHC was used as the Reference Standard. The proportion of test positives (accuracy) and the absolute agreements across pathologists (reproducibility) of the three grading strategies within each Reference Standard category were calculated.Results We found that immunoscoring with positivity definition 6 yielded the highest proportion of test positives for Reference Standard CIN3 (95.5%), in combination with the lowest proportion of test positives in samples with CIN1 (1.8%). The proportion of test positives for CIN3 was significantly lower for sole H&amp;E staining (81.8%) or combined H&amp;E and IHC grading (84.8%) with positivity definition ≥CIN3. Immunoscore 6 also yielded high absolute agreements for CIN3 and CIN1, but the absolute agreement was low for CIN2.Conclusions The higher accuracy and reproducibility of the immunoscore opens the possibility of a more standardised and reproducible definition of CIN grade than conventional pathology practice, allowing a more accurate comparison of CIN-based management strategies and evaluation of new biomarkers to improve the understanding of progression of precancer from human papillomavirus infection to cancer. ER -