Smear misclassification in a cervical cancer screening programme

Abstract

Summary A nested case-control study was undertaken in the Maribo County cohort of 27,811 women with negative Pap smears. Sixty women who later developed invasive cervical cancer constituted the cases, and five matched controls were selected from the cohort for each case. A total of 633 previous, negative smears for the cases and controls were reviewed independently by two pathologists. The review showed misclassification to be frequent in these smears collected in the period 1966-82. Thirty-five smears were considered positive at the review. The misclassification was differential in respect to the women's later disease status. The odds ratio for patients compared with controls for having at least one positive smear was 22.12 Materials and methods CohortIn the cohort study all smears taken in the Maribo County in the years 1966-1982 among women born 1918-1952 were registered. Both smears taken within the organised screening programme and all other smears taken as part of the clinical work by general practitioners, private gynaecologists, and hospital wards were included.All women with at least one smear were followed up for death and emigration in the Central Population Register, for cases of invasive cervical cancer in the computerised files of the local department of pathology and in the Danish Cancer Register, and for operations causing surgical removal of the cervix uteri in the Danish Hospital Discharge Register and in questionnaire data collected at the screening rounds. A cohort was thus identified of 27,811 women, who originally had negative smears. CasesA total of 60 cases of invasive cervical cancer was registered in this cohort when the follow-up was extended to include 1984. These 60 women constitute the cases. ControlsFor each case, five women were selected as controls from the cohort. Those five women were selected, who came closest to the case in date of birth, had the first negative smear in the same year as the case, had the same number of negative smears, had not developed a precancerous lesion of the cervix uteri, and had been followed up with the cervix uteri intact for at least the same time interval since the last negative smear as the case.Histology review Slides from the paraffin blocks based on which the original diagnoses were made were reviewed by two pathologists (EA and PP). Only those cases for which invasive growth was confirmed at the review remained as cases in the further analysis.Cytology review All previous negative smears for cases and controls were reviewed blindly by two pathologists (EA and PP). Slides with dots from the cytotechnicians' original evaluation were registered, and the dots were removed with ethanol before the review. Smears were classified as being satisfactory or unsatisfactory for evaluation of CIN. A satisfactory smearCorrespondence: E. Lynge.

Estimating the sensitivity of cervical cytology: errors of interpretation and test limitations

“…Under formal criteria of adequacy seven false-negative smears were not significantly different from as many true-negative and true-positive ones. Although based on sparse data this result is consistent with previous studies [21][22][23] suggesting that strict criteria for adequacy will strongly increase the rate of repeat smears without seriously affecting sensitivity. Moreover, it suggests that a relevant proportion of non-misinterpreted false-negative smears are not the result of inadequate smear-taking.…”

Screening history of women with cervical cancer: a 6-year study in Aarhus, Denmark

“…A similar false-negative rate has been reported recently (Spence et al, 2007) and in an earlier Danish study (Ingeholm and Glenthoj, 1996). We found a significant difference in favour of PAP smears with inflammation in group 3, an obscuring factor that may lead to misinterpretation and underlines the importance of high smear quality (Skehan et al, 1990;Sherman and Kelly, 1992;Lynge et al, 1993;Lyall and Duncan, 1995).…”

False-negative results in screening programmes: systematic review of impact and implications.

“…The impact of this is highlighted in a Danish case-control study, which reviewed the history of negative smears for women with invasive cervical cancer and a set of matched controls. 50 It concluded that the proportion of preventable cases of invasive cervical cancer could be increased from 62-72% to 83-86% if misclassification of smears could be avoided.…”