Cytologic diagnosis of atypical squamous cells of undetermined significance in perimenopausal and postmenopausal women - Lessons learned from human papillomavirus DNA testing

BACKGROUND. The authors have noted that in cervical cytology specimens from perimenopausal and postmenopausal women, the diagnosis of atypical squamous cells of undetermined significance (ASC-US), as defined in the Bethesda system, is often not associated with a clinically evident lesion on follow-up. Reflex human papillomavirus (HPV) testing provides an opportunity to distinguish cytologic features of significance from those within the spectrum of benign cellular change in this age group. METHODS. Liquid-based preparations that were diagnosed as ASC-US between January 2003 and July 2005 at Emory University Hospital were identified from the computer files. The results of HPV-DNA testing were recorded. Two hundred four Papanicolaou tests from perimenopausal women (n = 81, 40-49 years) and postmenopausal women (n = 123, > 50 years) were reviewed in a blinded fashion. RESULTS. HPV-DNA results were available for 903 of 1044 patients diagnosed as ASC-US. Overall, 323 results (35.80%) were positive, 510 results (56.6%) were negative, and 70 results (7.8%) were indeterminate. In addition, 73% of ASC-US specimens in patients aged >= 40 years were negative for HPV DNA. The HPV-DNA detection rate dropped from 60% in the group ages 10 to 19 years to approximately 18% in the group aged > 50 years. A review of HPV-negative cases in the group aged > 40 years showed squamous cells with random nuclear enlargement. and slight hyperchromasia that likely were interpreted as ASC-US (based oil the cells that were dotted by the original reviewer). Nuclear grooves were frequent in these nuclei; and cytoplasmic halos, when present, usually were perinuclear. CONCLUSIONS. HPV-DNA detection in cervical cytology specimens has an inverse relation to patient age. A diagnosis of ASC-US in perimenopausal and postmenopausal women is likely to result in a negative HPV-DNA test in a significant proportion of patients. Enlarged nuclei with nuclear grooves and slight hyperchromasia are possibly the cause of ASC-US overdiagnosis in this age group.