The human false-negative rate of rescreening Pap tests. Measured in a two-arm prospective clinical trial

Routine quality control rescreening often is used to calculate the false-negative rate (FNR) of gynecologic cytology. Theoretic analysis suggests that this is not appropriate, due to the high FNR of rescreening and the inability to actually measure it. The authors sought to determine the FNR of manual rescreening in a large, prospective, two-arm clinical trial using an analytic instrument in the evaluation.

The results of the Autopap System Clinical Trial, encompassing 25,124 analyzed slides, were reviewed. The false-negative and false-positive rates at various thresholds were determined for routine primary screening, routine rescreening, Autopap primary screening, and Autopap rescreening by using a simple, standard methodology.

The FNR of routine manual rescreening at the level of atypical squamous cells of undetermined significance (ASCUS) was 73%, more than 3 times the FNR of primary screening; 11 cases were detected. The FNR of Autopap rescreening was 34%; 80 cases were detected. Routine manual rescreening decreased the laboratory FNR by less than 1%; Autopap rescreening reduced the overall laboratory FNR by 5.7%. At the same time, the false-positive rate for Autopap screening was significantly less than that of routine manual screening at the ASCUS level (4.7% vs. 5.6%; P < 0.0001). Rescreening with the Autopap system remained more sensitive than manual rescreening at the low grade squamous intraepithelial lesions threshold (FNR of 58.8% vs. 100%, respectively), although the number of cases rescreened was low.

Routine manual rescreening cannot be used to calculate the FNR of primary screening. Routine rescreening is an extremely ineffective method to detect error and thereby decrease a laboratory's FNR. The Autopap system is a much more effective way of detecting errors within a laboratory and reduces the laboratory's FNR by greater than 25%.