Comparative Accuracy of Anal and Cervical Cytology in Screening for Moderate to Severe Dysplasia by Magnification Guided Punch Biopsy: A Meta-Analysis

Abstract

BackgroundThe accuracy of screening for anal cancer precursors relative to screening for cervical cancer precursors has not been systematically examined. The aim of the current meta-analysis was to compare the relative accuracy of anal cytology to cervical cytology in discriminating between histopathologic high grade and lesser grades of dysplasia when the reference standard biopsy is obtained using colposcope magnification.Methods and FindingsThe outcome metric of discrimination was the receiver operating characteristic (ROC) curve area. Random effects meta-analysis of eligible studies was performed with examination of sources of heterogeneity that included QUADAS criteria and selected covariates, in meta-regression models. Thirty three cervical and eleven anal screening studies were found to be eligible. The primary meta-analytic comparison suggested that anal cytologic screening is somewhat less discriminating than cervical cytologic screening (ROC area [95% confidence interval (C.I.)]: 0.834 [0.809–0.859] vs. 0.700 [0.664–0.735] for cervical and anal screening, respectively). This finding was robust when examined in meta-regression models of covariates differentially distributed by screening setting (anal, cervical).ConclusionsAnal cytologic screening is somewhat less discriminating than cervical cytologic screening. Heterogeneity of estimates within each screening setting suggests that other factors influence estimates of screening accuracy. Among these are sampling and interpretation errors involving both cytology and biopsy as well as operator skill and experience.

Natural History of Anal Dysplasia in an HIV-Infected Clinical Care Cohort: Estimates Using Multi-State Markov Modeling

“…Cytology is known to lack sensitivity for detection of HSIL [7], but as we have argued elsewhere, HRA-directed punch biopsy is not itself a true gold standard [8]. There is considerable heterogeneity among reports of anal cytology sensitivity and specificity with HRA-directed biopsy as the reference standard and the pooled sensitivity for HSIL on biopsy using a cytology cut-point of (HSIL or ASC-H) vs (normal, ASCUS, or LSIL) was only 30% (95% CI: 19–44%) in a recent meta-analysis [27].…”

“…It is known, however, that both cytology and HRA-directed punch biopsy are imperfect indicators of true histopathologic severity in the anal canal [7], [8]. We therefore modeled state transitions using continuous time hidden Markov models, using the R package msm [9], [10], that account for misclassification due to the limitations of both cytology and HRA-directed punch biopsy.…”

A Composite Cytology–Histology Endpoint Allows a More Accurate Estimate of Anal High-Grade Squamous Intraepithelial Lesion Prevalence

“…Some researchers have advocated that a similar cytologybased screening and treatment program should be adopted for anal HSIL (8). However, the test performance of anal cytology continues to be debated (9). In particular, to achieve similar sensitivity to cervical screening, a lower abnormality threshold for referral for the diagnostic test [high-resolution anoscopy (HRA)-guided biopsy] is recommended by some (5).…”

“…In particular, to achieve similar sensitivity to cervical screening, a lower abnormality threshold for referral for the diagnostic test [high-resolution anoscopy (HRA)-guided biopsy] is recommended by some (5). Partly because of the lower threshold for referral, anal cytology is generally less specific than cervical screening (5,9). In addition, the diagnostic test, HRA-guided biopsy, is acknowledged as technically more difficult than cervical colposcopy and is therefore more likely to miss HSIL lesions, particularly if the anoscopist is relatively inexperienced with the procedure (10).…”

Relative Accuracy of Cervical and Anal Cytology for Detection of High Grade Lesions by Colposcope Guided Biopsy: A Cut-Point Meta-Analytic Comparison

“…We recently reported, using a receiver operating characteristic (ROC) area metric, the first meta-analytic comparison of the relative accuracy of cervical and anal cytology in detecting moderate or severe (high grade squamous intraepithelial lesion -HSIL) histopathologic lesions by magnification directed punch biopsy [4]. While ROC area is a useful summary measure of test discrimination, a more clinically useful metric would be based on test sensitivity and specificity at varying cytology cut-points.…”