Longitudinal Cytological Follow-up of Patients With a Papanicolaou Test Interpretation of "Atypical Squamous Cells of Undetermined Significance" That Was Followed by a Negative Reflex Test for High-Risk Human Papillomavirus Types

Abstract

The 2001 consensus guidelines essentially equated the follow-up management of patients with a Papanicolaou (Pap) test interpretation of negative for intraepithelial lesion or malignancy and those with an interpretation of atypical squamous cells of undetermined significance (ASC-US) that was followed by a negative reflex test for high-risk human papillomavirus (HR HPV) types: follow-up cytology in 12 months. As several years have elapsed since these guidelines attained some measure of widespread implementation, we sought to determine whether, in routinely diagnosed cases, the full spectrum of follow-up cytological findings are indeed identical in these 2 groups. Clinical and pathological data of consecutive patients with a Pap test interpretation of ASC-US during a 6-week period (n = 587), in which reflex human papillomavirus testing was performed (n = 497) and in which HR HPV types were not detected (n = 300), were reviewed (study group). A randomly selected control group of 300 patients whose Pap tests were reported as negative (negative for intraepithelial lesion or malignancy) during the same period were similarly reviewed. The follow-up Pap tests were classified into the various Bethesda 2001 diagnostic categories, and both groups were compared. The average follow-up duration in the study and control groups was 26.03 and 25.9 months, respectively. When all of the follow-up Pap tests in each group (study, n = 555; control, n = 356) were used for the comparisons, patients in the study group were significantly more likely to have an abnormal follow-up Pap test result than the control group patients (24.9% vs 7.6%, P < 0.0001); this was primarily attributable to the more frequent repeat interpretations of ASC-US in the former group (20.5% vs 5.1%, P < 0.0001). The HR HPV detection rates in the follow-up ASC-US cases were not significantly different between the study and control groups. There were no significant differences between both groups regarding the diagnostic frequencies of low-grade squamous intraepithelial lesion and atypical squamous cells-cannot exclude high-grade squamous intraepithelial lesion (HGSIL). No examples of HGSIL or invasive cancer were identified in the follow-up of either group. All comparisons of statistical significance retained their significance when only 1 follow-up Pap test per patient, the most severe interpretation, was used. Our findings suggest that some significant differences exist between these 2 groups, most notably the comparatively increased frequency of repeat ASC-US interpretations in the study group. However, the extraordinary rarity of the most clinically significant interpretations of HGSIL and carcinoma in this setting can be confirmed because no such cases were identified during the follow-up of either group.