Three-tiered score for Ki-67 and p16 improves accuracy and reproducibility of grading CIN lesions.

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 p16.

METHODS

115 cervical tissue specimens were reviewed by three expert gynaecopathologists and graded according to three strategies: (1) CIN grade based on H&E staining only; (2) immunoscore based on the cumulative score of Ki-67 and p16 only (0-6); and (3) CIN grade based on H&E supported by non-objectified IHC 2 weeks after scoring 1 and 2. The majority consensus diagnosis of the CIN grade based on H&E supported by IHC was used as the . The proportion of test positives () and the absolute agreements across pathologists () of the three grading strategies within each category were calculated.

RESULTS

We found that immunoscoring with positivity definition 6 yielded the highest proportion of test positives for (95.5%), in combination with the lowest proportion of test positives in samples with (1.8%). The proportion of test positives for was significantly lower for sole H&E staining (81.8%) or combined H&E and IHC grading (84.8%) with positivity definition ≥CIN3. Immunoscore 6 also yielded high absolute agreements for and , but the absolute agreement was low for .

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.