Journal Article

p16INK4a immunostaining as an alternative to histology review for reliable grading of cervical intraepithelial lesions

Rozendaal, Lawrence, Dijkstra, Maaike G, Heideman, Daniëlle A M, Berkhof, Johannes, van Groningen, Krijn, Snijders, Peter J F, de Roy, Sabine C, Meijer, Chris J L M, van Krimpen, Kees, van Kemenade, Folkert J

2010

Overview

BackgroundHistomorphological grading of cervical intraepithelial neoplasia (CIN) is crucial for clinical management. CIN grading is however subjective and affected by substantial rates of discordance among pathologists, which may lead to overtreatment. To minimise this problem, a histology review of CIN lesions by a consensus panel of pathologists is often used. Diffuse strong p16INK4a immunostaining has been proposed to aid the identification of true high-grade cervical lesions (ie, CIN2/3).AimTo assess the value of additional interpretation of p16INK4a immunostains for making a more reproducible diagnosis of CIN2/3 lesions.MethodsThe authors used a series of 406 biopsies of cervical lesions, with known HPV status, stained for both H&E- and p16INK4a. First, in a randomly selected set of 49 biopsies, we examined the effect of additional interpretation of p16INK4a immunostained slides, on the agreement of CIN diagnosis among three pathologists. Second, the full series of samples was used to assess the accuracy of p16INK4a-supported lesion grading by a single pathologist, by evaluating the degree of diagnostic agreement with the consensus diagnosis of expert pathologists based on H&E-stained sections only.ResultsThe study shows that the interobserver agreement between three pathologists for the routine H&E-based diagnosis ranged from fair (weighted kappa 0.44 (95% CI 0.19 to 0.64)) to moderate (weighted kappa 0.66 (95% CI 0.47 to 0.79)). The concordance increased substantially for p16INK4a-supported grading (mean weighted kappa 0.80 (95% CI 0.66 to 0.89)). Furthermore, an almost perfect agreement was found between the p16INK4a-supported diagnosis of a single pathologist and the consensus diagnosis of an expert pathology panel (kappa 0.88 (95% CI 0.85 to 0.89)).ConclusionsThese data demonstrate that additive use of p16INK4a immunohistochemistry significantly improves the accuracy of grading CIN lesions by a single pathologist, equalling an expert consensus diagnosis. Hence, the authors advocate the combined use of p16INK4a-stained slides and conventional H&E sections in routine histopathology to improve accuracy of diagnosis.

• Publisher: BMJ Publishing Group Ltd and Association of Clinical Pathologists,BMJ Publishing Group,BMJ Publishing Group LTD
• Subject: Accuracy / Agreements / Biological and medical sciences / Cervical cancer / cervical intraepithelial neoplasia / CIN / grading / Histology / histomorphological diagnosis / Histopathology / HPV / HPV DNA testing / Human papillomavirus / immunohistochemistry / Investigative techniques, diagnostic techniques (general aspects) / Medical sciences / p16INK4a immunohistochemistry / Pathology / Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques / Studies