False negative colposcopy is associated with thinner cervical intraepithelial neoplasia 2 and 3

ObjectiveTo assess whether thinner lesion epithelium or lower nuclear density contribute to false negative colposcopy for dysplasia, we determined epithelial thickness and nuclear density and correlated this with the accuracy of colposcopic impression for cervical quadrants with biopsies of normal, CIN 1, CIN 2 and CIN 3.MethodsThe thickness and nuclear density of squamous epithelium of 261 selected cervical biopsies (CIN 2/CIN 3, N = 144; Normal/CIN 1, N = 117) from the Shanxi Province Cervical Cancer Screening Study (where a colposcopic impression and biopsy were obtained in each cervical quadrant) were measured. Average epithelial thickness was defined as the thinnest area plus the thickest area divided by two. Average nuclear density was defined as the number of nuclei in a 2,500 µm2 grid at the junction of the superficial and intermediate zones plus that at the junction of the intermediate and parabasal zones divided by two. Differences in means were measured by Wilcoxon Rank-Sum Test. Trends among means were measured by a generalized linear mixed model.ResultsMean average epithelial thickness for 33 biopsies of CIN 2/CIN 3 from cervical quadrants with colposcopic impression of normal (184 µm) was less than that of 111 biopsies of CIN 2/CIN 3 from quadrants with colposcopic impressions of low, high, or cancer (321 µm, p < .001). CIN 2/CIN 3 had higher mean average nuclear density (p < .001) and was thinner than normal/CIN 1 (p < .001).ConclusionThe inability of expert colposcopists to visualize some CIN 2/CIN 3 is associated with thinner epithelium.