Why are Polish women diagnosed with invasive cervical cancer after negative cytology in the organized screening programme – a pilot reevaluation of negative Pap smears preceding diagnoses of interval cancers

Abstract

We have aimed to study reasons for reporting false-negative cytology results preceding diagnosis of interval cervical cancers (CC) in Poland. Data on all Pap smears collected in the organised screening in 2010-2015 were retrieved from the electronic database and linked with Polish National Cancer Registry (PNCR) data. False-negative results were defined as those sampled and assessed normal up to 3.5 years before diagnosis of invasive CC. False-negative slides were then seeded among twice as many randomly selected slides from the same lab and reviewed independently by three expert cytomorphologists. New diagnosis was established when experts agreed on a result. Of 48 selected false-negative slides, 1 case was diagnosed as a low-grade abnormality, 22 cases as a high-grade abnormalities, 3 cases as unsatisfactory for evaluation and 5 as no intraepithelial lesion of malignancy (NILM) by all three experts. There was no agreement in 17 cases. Percentages of agreement between experts was 64.6. Interobserver agreement rate was moderate with Fleiss' κ values. Our pilot study indicates evaluation errors as the main reason of false-negative cytology preceding interval CC in the organized screening programme in Poland. True lack of abnormal cells on the slide is the next reason.

False Negative Results in Cervical Cancer Screening—Risks, Reasons and Implications for Clinical Practice and Public Health

“…Interpretation of a slide as normal, despite the presence of abnormal cells, was pointed out as a reason for FN diagnoses in over 50% of slides in many studies. In a pooled analysis by DeMay, 655 no intraepithelial lesions or malignancy (NILM) slides were evaluated, and 340 of them were reclassified as abnormal (51.9%) [ 42 ], which was in line with results obtained by Kenter et al (53.3%) [ 43 ], Bulk et al (61.1%) [ 44 ], and, more recently, Komerska et al (54.2%) [ 45 ]. Other researchers, however, reported the rate of misinterpretation as low as 4.6% to 15% [ 46 , 47 , 48 ].…”

“…According to Sherman et al, among 18 patients with an overall 123 multiple normal slides preceding CIN3+ diagnosis, 7 had at least 2 slides reclassified as unsatisfactory for evaluation (38.9%) [ 51 ]. In an audit of FN in Poland, only 3 amongst 48 re-evaluated normal slides preceding CC diagnosis were reclassified by all three experts as unsatisfactory for evaluation (6.3%) [ 45 ].…”

Reasons for truly negative cytology reports preceding the diagnoses of invasive cervical cancer—Results of a false‐negative cytology audit in Polish Cervical Cancer Screening Programme

“…Laboratories refused or were unable to provide a part of slides and overall 431 FNs and 960 blinding slides were handed over and reassessed by all three expert pathologists. Due to unconfirmed cancer invasion status, nine cases were excluded from analysis as well as subsequent 48 FN and 94 blinding slides acquired in 2018 and reassessed by different experts as these results were published elsewhere 12 . Overall, 374 potential FNs and 866 blinding slides were left (61.0% and 70.6%, respectively).…”

“…The pilot results suggested the need for more in-depth investigation of assessment quality and corrective actions. 12 The aim of this study was to analyse the results of FN audit which took place in 2019-2021 in Poland and to seek for reasons of FNs occurrence as well as for potential risk factors of obtaining truly negative cytology results preceding diagnosis of ICs, defined as FNs confirmed as no intraepithelial lesions or malignancy (NILM) by experts' evaluation. Auditors' concordance will also be discussed.…”

“…In only 10% cases, the screening result was confirmed as NILM and 6% slides were considered unsatisfactory for evaluation. The pilot results suggested the need for more in‐depth investigation of assessment quality and corrective actions 12 …”