Inter‐ and intra‐observer variation in the histopathological reporting of cervical squamous in traepithelial lesion susing a modified Bethesda grading system

Abstract

Objective 1. To assess inter-and intra-observer variation in the histopathological reporting of cervical colposcopic biopsies using a histologic modification of the cytological Bethesda grading system; 2. to determine the histologic profile of those cases which resulted in diagnostic disagreement.Methods Consecutive cervical colposcopic biopsies (n = 125) were assessed independently by six experienced histopathologists. Cases were classified as normal, low grade squamous intraepithelial lesion or high grade squamous intraepithelial lesion. Six months later the process was repeated. The degree of inter and intra-observer variation was assessed by kappa statistics. All cases in which there was less than perfect inter and intra-observer agreement were reviewed by the coordinator of the study. ResultsIn the first round of the study inter-observer agreement was generally poor, with unweighted and weighted kappa values ranging from 0.15 to 0.58 (average 0.30) and from 0.21 to 0.61 (average 0.36) respectively. In the second round inter-observer agreement was better, with unweighted and weighted kappa values ranging from 0.08 to 0.55 (average 0-33) and from 0.22 to 0.59 (average 0.42). Ten of the 15 pairs of observers achieved fair inter-observer agreement using weighted kappa analysis. The degree of intra-observer agreement was better, unweighted and weighted kappa values ranging from 0.26 to 0.61 (average 0.47) and from 0.34 to 0.62 (average 0-51) respectively. Two of the six participants achieved fair intra-observer agreement and two achieved good intra-observer agreement using weighted kappa analysis. There were marked difficulties in the separation of normal squamous epithelium from low grade squamous intraepithelial lesion and in the separation of low grade from high grade squamous intraepithelial lesions. Histopathological review revealed that many of the difficulties in the separation of normal and low grade squamous intraepithelial lesion were in the distinction between superficial vacuolated cells and true koilocytes. Difficulties also resulted in the separation of basal cell hyperplasia, inflammatory associated changes and immature squamous metaplasia from low grade squamous intraepithelial lesion. Conditions which resulted in difficulty in the separation of low grade and high grade squamous intraepithelial lesions included florid koilocytotic change and immature metaplastic squamous epithelium with atypia. In some cases, there was a full spectrum of diagnoses from normal to high grade squamous intraepithelial lesion. These were largely cases of immature metaplastic squamous epithelium with atypia and of thin or atrophic squamous epithelium with atypia.Conclusions Most pairs of observers can achieve fair inter-observer agreement in the reporting of cervical colposcopic biopsies using a modified Bethesda system. Intra-observer agreement is also generally fair to good using this system. It may be that a two tier grading system is more appropriate for the histopathological reporting of these biopsies than the tr...

Impact of utilizing p16INK4A immunohistochemistry on estimated performance of three cervical cancer screening tests

“…16,20 Numbers do not add up to totals due to missing data and are as shown. Cases of invasive cervical cancer are not included.-2 v 2 test for trend except for median RLU value that is by Kruskall-Wallace test.-3 P0 is ''warrants colposcopy'' diagnosis.- 4 If high-risk HPV DNA positive by hc2, RLU is relative light units that is an indicator of HPV DNA content or viral load. In our study, we observed good correlation between p16 INK4A immunohistochemical staining and a consensus pathological diagnosis of CIN 2,31, consistent with what has been shown previously in the literature.…”

“…3 This results in marked difficulties in separating normal biopsies from CIN 1 and in distinguishing between CIN 1 and CIN 2,3 based on histopathology alone. 4 Recognition of this variability has led to concerted efforts to identify novel biomarkers capable of more reproducibly distinguishing between normal and CIN lesions and in reducing the variability in grading of CIN lesions. A number of potentially diagnostically useful biomarkers have been identified using conventional immunohistochemical approaches and tissue microarrays.…”

“…This is documented by numerous studies investigating intraobserver and interobserver variability among groups of pathologists evaluating cervical biopsies. [1][2][3][4] In general, agreement between pathologists is excellent for invasive lesions, moderately good for CIN 3 and poor for CIN 1 and CIN 2. 3 This results in marked difficulties in separating normal biopsies from CIN 1 and in distinguishing between CIN 1 and CIN 2,3 based on histopathology alone.…”

The Lower Anogenital Squamous Terminology Standardization Project for HPV-Associated Lesions: Background and Consensus Recommendations from the College of American Pathologists and the American Society for Colposcopy and Cervical Pathology

“…As expected, classification agreement with lower variability between observers can be improved in a 2-tiered versus a 3-tiered system [10,28,[78][79][80][81][82][83][84][85][86][87]. Improved agreement among pathologists leads to a more consistent and reproducible diagnosis, which may lead to more valid clinical outcome data.…”

Overexpression of p16INK4A as a specific marker for dysplastic and neoplastic epithelial cells of the cervix uteri

“…15,16 In women with abnormal smears, histological analysis of biopsy samples is used to establish the definitive diagnosis of the underlying lesion. However, as for cytology, histology is also affected by a substantial rate of interobserver discrepancies even among a panel of expert pathologists, 17 suggesting that objective and clearly decisive biomarkers would also improve standardization and vigorous quality control of the histological diagnosis.…”