How should we grade CIN?

Abstract

How should we grade CIN? The grading of cervical intraepithelial neoplasia (CIN) is problematic. CIN represents a morphological continuum, but biopsies displaying this lesion are classified into two (e.g. Bethesda) or three grade categories, sometimes with poor reproducibility. There are also difficulties in reliably distinguishing low-grade CIN from its reactive simulants. Because of problems with inter- and intra-observer disagreement in the grading of CIN and the diagnosis of low-grade lesions, three expert contributions were commissioned to address the question 'how should we grade CIN?'.

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

“…In the new millennium, there has been renewed debate about adopting a 2-tiered low-grade and high-grade terminology for all LAT HPV-associated intraepithelial lesions [34][35][36]. The primary concern regarding adopting a 2-tiered system for the cervical histology is that guidelines for management of CIN 2, 3 in adolescents and young women promoted expectant management of CIN 2 with the option to follow lesions reported as CIN 2, 3 but not CIN 3 [33,37,38].…”

Uterine cervical carcinoma: Role of matrix metalloproteinases (Review)

“…Another serious disadvantage is due to the three distinct grades used in CIN (or two in SIL) that can easily give a faulty static impression of a solidified sculpture as if CIN or SIL were a static event, whereas in reality a CIN lesion is a dynamic process that can progress and persist but also regress. Compounding the above are the well-known issues of intraobserver and interobserver reproducibility, which, for grading of CIN, is far from perfect (5,6). It is also difficult to distinguish CIN reliably from non-neoplastic lesions, resulting in either over-treatment or undertreatment (7,8).…”

Variability of Pathologists' Utilization of p16 and Ki-67 Immunostaining in the Diagnosis of Cervical Biopsies in Routine Pathology Practice and Its Impact on the Frequencies of Cervical Intraepithelial Neoplasia Diagnoses and Cytohistologic Correlations

“…Internal controls (bglobin) were run on each sample, and positive and negative controls, including low-quantity controls, were included with each run. Human papillomavirus results were reported as positive for hr-HPV if HPV type(s) 16,18,31,33,35,39,45,51,52,56,58,59, or 68 were identified, and negative for hr-HPV when no HPV or any other HPV type(s) were identified. The presence of low-risk HPV types was included in a comment.…”

“…30 Despite the apparent simplicity of the criteria used for the diagnosis and grading of CIN, even experts may disagree on their practical application. 31,32 The large interobserver variability found by multiple studies makes it clear that pathologists encounter significant challenges in the diagnosis and grading of CIN. This may be due to technical factors (small biopsy sample; poor processing, staining, or sectioning; poor orientation; incomplete representation; significant epithelial denudation; thermal, crush, and other artifacts), patient-related factors (pregnancy, postpartum status, menopause, exogenous hormone administration, coexistent infections, prior radiation), or to pathologistrelated factors.…”