False negative rate of cervical cytologic smear screening as determined by rapid rescreening.

OBJECTIVE: To determine the reliability of the false negative rate (FNR) of cervical cytologic smear screening by rapid rescreening. STUDY DESIGN: A test set of 401 cases (311 originally diagnosed as negative, 74 as atypical squamous cells of undetermined significance [ASCUS], 14 as low grade squamous intraepithelial lesion [LSIL] and 2 as high grade squamous intraepithelial lesion [HSIL]) were rapidly (30 seconds each) rescreened by five cytotechnologists with no prior experience in rapid rescreening, and the FNRs of rapid rescreening and primary screening were determined. These results were compared with each other and with the FNR of primary screening as determined by routine rescreening of all cases with no time limit. RESULTS: All five observers detected a different group of abnormal cases; only 9% of all cases originally diagnosed as ASCUS or worse and 43% of all cases diagnosed as LSIL or worse were detected by all five observers. Nevertheless, using ASCUS as the threshold for an abnormal result, the FNR of rapid rescreening fell into a relatively narrow range, 61-74% (mean, 68.2 +/- 5.0); using LSIL as the threshold resulted in FNRs of rapid rescreening between 25% and 38% (30.0 +/- 4.7). Each observer, using rapid rescreening, detected between one and three false negative cases; routine rescreening of all cases without a time limit detected five cases. The FNR of cervical cytologic smear screening, as determined by rapid rescreening, was 18.4 +/- 6.1% as compared with 14.8% by routine rescreening without a time limit. CONCLUSION: The FNR of rapid rescreening is relatively reproducible even though the individual cases identified varied between reviewers. The FNR of rapid rescreening is similar to that of routine rescreening. Rapid prescreening may be the most logistically simple method to determine the true FNR of a laboratory.

Cytologic characteristics of abnormal cells in prior "normal" cervical/vaginal Papanicolaou smears from women with a high grade squamous intraepithelial lesion.

BACKGROUND: Some cervical/vaginal Papanicolaou (Pap) smears previously diagnosed as normal in women with a high grade squamous intraepithelial lesion (HSIL) are found to contain abnormal cells on retrospective review. This study characterized and quantitated such cells in 100 Pap smears. METHODS: One hundred prior negative Pap smears from 49 women with a newly diagnosed HSIL were rescreened, as were 107 negative Pap smears from 100 women with normal subsequent smears. Cases were assorted randomly so that the rescreener was unaware of the subsequent follow-up. RESULTS: All 12 Pap smears found to contain atypical mature and immature metaplastic cells belonged to the group with a subsequent HSIL (P = 0.001). In addition, 18 of the 100 previously negative Pap smears (18%) had immature metaplastic cells without nuclear atypia compared with 4 of 107 Pap smears (4%) in the control group (P = 0.0007). CONCLUSIONS: This study supports the observations of other authors that atypical metaplastic cells, especially those of the immature type, are associated with HSIL. These cells most likely are HSIL lesional cells, which are not easily recognizable as such. Immature metaplastic cells without atypia also were shown to be associated significantly with HSIL in this study. These cells may be unrecognizable lesional cells or a marker of increased risk for HSIL and deserve further study.

A more accurate measure of the false-negative rate of Papanicolaou smear screening is obtained by determining the false-negative rate of the rescreening process.

BACKGROUND: The false-negative rate (FNR), or fraction, of Papanicolaou (Pap) smear screening has been proposed as a useful quality assessment measure. The FNR should account for the FNR of the rescreening process itself. The authors measured the FNR of the rescreening process by rescreening a set of abnormal smears. METHODS: A randomly selected group of negative (150) and abnormal (91) smears were rescreened in a blinded fashion. A diagnosis of atypical squamous cells of undetermined significance (ASCUS) or worse was used as a positive (abnormal) result. All discrepancies were confirmed by consensus review. The true FNR of screening Pap smears was calculated as: true FNR = calculated FNR/(1-FNR of rescreening). RESULTS: When rescreened, 17 originally negative cases were interpreted as ASCUS and 5 as unsatisfactory. Twenty-three originally abnormal cases (22 ASCUS and 1 low grade squamous intraepithelial lesion) were interpreted as negative. After consensus review, only 1 of the originally negative cases was believed to be ASCUS and 1 unsatisfactory; 18 of the 23 originally abnormal cases were believed to be rescreening errors and 5 of the 23 originally abnormal cases were believed to be false-positives. The FNR of Pap smear screening as traditionally calculated was 6.1%, which was slightly less than the laboratory's usual FNR. The FNR of review screening was 20.9%. The true FNR of Pap smear screening was 7.8% and the false-positive rate was 0.6%. CONCLUSIONS: The FNR of rescreening is not insubstantial. It can and should be measured by rescreening abnormal smears, and when taken into account yields a more accurate measure of the FNR of Pap smear screening.