Papanicolaou test in the detection of high-grade cervical lesions: a re-evaluation based on cytohistologic non-correlation rates in 356 concurrently obtained samples.

Studies evaluating the routine Papanicolaou (Pap) test have traditionally used as the reference gold standard, the diagnoses on the follow-up histologic samples. Since the latter are typically obtained days to weeks after the Pap test, the accuracy of the resultant comparison may be affected by interim factors, such as regression of human papillomavirus, new lesion acquisitions or colposcopy-associated variability. A subset of our clinicians have routinely obtained cervical cytology samples immediately prior to their colposcopic procedures, which presented a unique opportunity to re-evaluate the test performance of liquid-based cervical cytology in detecting the most clinically significant lesions (i.e. cervical intraepithelial neoplasia 2 or worse: CIN2+), using as gold standard, diagnoses on cervical biopsies that were essentially obtained simultaneously. For each patient, cytohistologic non-correlation between the Pap test and biopsy was considered to be present when either modality displayed a high-grade squamous intraepithelial lesion (HGSIL)/CIN2+ while the other displayed a less severe lesion. Therefore, HGSIL/CIN2+ was present in both the Pap test and biopsy in true positives, and absent in both modalities in true negatives. In false positives, the Pap test showed HGSIL while the biopsy showed less than a CIN2+. In false negatives, Pap tests displaying less than a HGSIL were associated with biopsies displaying CIN2+. Combinations associated with "atypical" interpretations were excluded. A cytohistologic non-correlation was present in 17 (4.8%) of the 356 combinations reviewed. The non-correlation was attributed, by virtue of having the less severe interpretation, to the Pap test in all 17 cases. There were 17, 322, 0, and 17 true positives, true negatives, false positives and false negatives respectively. The sensitivity, specificity, positive predictive value and negative predictive value of the Pap test, at a diagnostic threshold of HGSIL, in identifying a CIN2+ lesion were 50%, 100%, 100% and 95% respectively. Even in Pap test/biopsy combinations obtained on the same day by the same colposcopist and evaluated by the same pathologist, there is a 4.8% (17/356) false negative rate associated with the Pap test. Our findings suggest that there may be an intrinsic error rate associated with this test modality.