Appendix A. False Negatives and False Negative Rates (FNRs): A
Review
The literature cites an astounding range of laboratory FNRs,
from less than 1% to 93%. In some studies, however, the reported
FNR was actually the percentage of negative smears found to be
positive or abnormal on review. In other studies, false-negative
cases were based on a review diagnosis of ACUS rather than SIL
when the initial diagnosis was negative; although the former is
often used for a laboratory's internal review, only the latter is
appropriately used for external evaluation of a laboratory. In
addition, although an accurate laboratory FNR is based on random
rescreening of a laboratory's cases, some published Pap smear
rescreening studies focused on specimens collected from patients
at high risk for developing cervical cancer or patients who were
subsequently clinically diagnosed with SIL or carcinoma. Any
reported laboratory FNR must be analyzed carefully to determine
whether the value was accurately determined (Table_2). Table_2 Note:
To print large tables and graphs users may have to change their printer settings to landscape and use a small font size.
TABLE 2. Study results on rescreening of Pap smears initially diagnosed as negative
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Reference Setting No. of Pap smears Description of samples* Threshold+ Smears found to be False negative
rescreened false negative rate
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Yobs et al. (16 ) 2 University- based 19,474 Consecutive smears,excluding SIL 2.0% 30%
medical centers cases with original diagnosis
of unsatisfactory or diagnoses
associated with glandular
abnormalities
Allen et al. (17 ) 2 University teaching 80 Smears from patients who had SIL ACUS 7.5% 15.0% 17.5%
hospital laboratories had all negative smears within Unsatisfactory
5 years of diagnosis of high-
grade SIL or carcinoma
Sherman & Kelly (18 ) University teaching 123 All available smears from 20 SIL ACUS 22.7% 52.7% 66.7%
hospital laboratory women with >=3 negative smears Unsatisfactory
preceding a diagnosis of high-
grade SIL or carcinoma
Nick et al. (19 ) University teaching 351 All available negative smears Unsatisfactory 70.7%
hospital laboratory from 143 women within 5 years
of diagnosis of high-grade SIL
Gatscha et al. (20 ) University teaching 3,962 From 1 year,random sample and Not stated 0.28%
hospital targeted rescreen of smears of
high-risk patients
422 All available smears in the 5 ACUS 25.8% 28.7%
years preceding histologically Unsatisfactory
confirmed high-grade SIL or
carcinoma
Tabbara & Sidawy (21 ) University teaching 2,124 Random sample; rescreening was ACUS 0.2% 1.6%
laboratory performed by a cytopathology
fellow
Slagel et al. (22 ) University laboratory 435 Consecutive smears from a high- SIL ACUS 0.7% 3.4% 9.4% 25.0%
risk patient population;
automation- assisted
rescreening
Dean (23 ) Teaching laboratory All available negative smears Unsatisfactory 18%-29%
in the 5 years preceding
diagnosis of high-grade SIL or
carcinoma
Hatem & Wilbur (24 ) 2 Teaching centers 17 Smears from patients who had SIL ACUS 64.7% 94.1%
had a negative smear in the 2
years preceding a diagnosis of
high-grade SIL or carcinoma
Wang (25 ) Community hospital ~200 Combination of random smears SIL 3.4%
laboratory and smears in the 5 years
preceding a cytologic
diagnosis of high-grade SIL or
carcinoma
19,623 Both random samples and SIL 0.48%
consecutive smears
Personal communication,SE Wang Community hospital All smears from 1 year SIL <12.5%
to ML Nielsen laboratory
Krieger & Naryshkin (10 ) Community hospital Quarterly random sampling ACUS 0%-17%
Inhorn & Shalkham (26 ) State laboratory Random sample from 1 year ACUS 0.7% 9.0%-11.7%&
All smears from 1 year from a ACUS 1.5%
high-risk patient population
All available smears in the 5 ACUS 13.6%
years preceding cytologic
diagnosis of high-grade SIL or
carcinoma
Colgan et al. (27 ) Independent laboratory 3,477 Consecutive smears SIL ACUS 0.4% 2.4% 12.7%
Krieger & Naryshkin (10 ) Independent laboratory >=1,000,000 Random sample from 15 years ACUS 0.3%-0.7%& 4%-11%
Jones (28 ) 312 Laboratories 3,762 From responding laboratories SIL ACUS 10.1% 19.9%
Unsatisfactory 20.4%
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* All smears rescreened were initially diagnosed as negative.
+ A false-negative cytology smear is identified when positive cells are found on rescreening of a smear initially reported to be negative. For external review, a minimum
diagnosis of squamous intraepithelial lesions (SIL) on rescreening serves as the threshold for identifying a false negative. For a laboratory's internal review, the
threshold is often set at atypical cells of undetermined significance (ACUS). The ACUS threshold includes SIL false negatives, and the Unsatisfactory
threshold includes ACUS and SIL thresholds.
& Approximated study data.
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