Although the false-negative rate (FNR) is the most important quality control measure for Papanicolaou smear screening, accurate, precise, and feasible methods for determining this value are lacking.
The author undertook an analysis and review of the literature.
The best estimates of the FNR using atypical squamous cells of undetermined significance (ASCUS) as a threshold range from 17% to 61%. Sources of error in the accuracy of this measure that must be accounted for include the FNR of the review method, differences in diagnostic thresholds between the original diagnostic method and the review method, and differences in diagnostic accuracy between the original diagnostic method and the review method. Statistically precise (valid to within 10%) measurement of this value in laboratories with an ASCUS+ rate of 7% can be made from interlaboratory rescreening of approximately 1200-1500 randomly selected normal and abnormal slides along with both laboratories rediagnosing without rescreening 300-400 benign cellular change and ASCUS slides to determine the difference in diagnostic threshold. Consensus for each slide is not required with this method. Changing the threshold to low grade squamous intraepithelial lesion (best estimate FNR, 14-58%) requires review of significantly more slides to achieve the same statistical level of precision.
Detailed analysis of the sources of error in determining the FNR allow creation of methods that are relatively unbiased, feasible, and testable and whose accuracy and precision can be determined.