p16 and Ki-67 immunohistochemical staining reduces inter- and intra-observer variability in the grading of cervical squamous intraepithelial lesions of South African women

Abstract

Background: Cervical carcinoma was the second leading malignancy in South African women (following breast carcinoma) in 2010. This study aimed to correlate histopathological criteria and immunohistochemical stains in terms of the grading of cervical intraepithelial precursor lesions and evaluate intra- and inter-observer variability with only histology and with additional immunohistochemical stains. Methods: Archival tissue from large-loop excision of the transformation zone (LLETZ) was graded on two separate occasions by an independent observer in terms of lesional severity. The section with the highest grade precursor lesion was selected and submitted for immunohistochemical stains that included p16 and Ki-67. These stains were also evaluated on two separate occasions by an independent observer. Results: This study showed kappa values of 0.47 and 0.46 respectively for the separate histological evaluations of the observer and the original pathology report. The kappa value for the two evaluations of the observer was 0.57. Thus inter- and intra-observer variability is fair with the use of routinely stained histological slides. The two Ki-67 assessments had a kappa value of 0.85 and the p16 had a value of 0.80. Intra-observer agreement was markedly higher when using immunohistochemistry. Conclusion: Although in most cases of precursor lesions of the cervix the grading can be made on routinely stained sections, intra- and inter-observer variability remains high. Immunohistochemical markers reduce this variability and aid in deciding in which group to place ambiguous lesions.