title: Cytologic diagnosis of atypical squamous cells of undetermined significance in perimenopausal and postmenopausal women: lessons learned from human Papillomavirus DNA testing.
abstract: 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 (35.8%) 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 > or =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 on 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.
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University Hospital, Atlanta, GA 30322, USA.
authors.forename: Elizabeth I
authors.initials: EI
authors.lastname: Johnston
authors.forename: Sanjay
authors.initials: S
authors.lastname: Logani
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D052685:Alphapapillomavirus / Q000235:genetics; D002648:Child; D003581:Cytodiagnosis / Q000379:methods; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D006801:Humans; D008875:Middle Aged; D018307:Neoplasms, Squamous Cell / Q000175:diagnosis* / Q000821:virology; D065006:Papanicolaou Test; D030361:Papillomavirus Infections / Q000175:diagnosis* / Q000821:virology; D047648:Perimenopause; D017698:Postmenopause; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000821:virology; D014626:Vaginal Smears / Q000379:methods
chemical_list: D004279:DNA, Viral