title: Managing atypical squamous cells of undetermined significance in Papanicolaou smears.
abstract: OBJECTIVE
  To assess strategies using repeated conventional Pap smear and human papillomavirus (HPV) DNA testing, alone or in combination, for identifying women with concomitant cervical intraepithelial neoplasia 2 and 3 (CIN 2/3) in women with atypical squamous cells of undetermined significance (ASCUS) in their Pap smears.
  
  
  METHODS
  A total of 360 women cytologically diagnosed with ASCUS were referred for colposcopy and underwent a repeat Pap smear, a biopsy when necessary and HPV testing using three different modes of detection of high-oncogenic-risk HPV types: 1, first-generation Hybrid Capture test (HC-1) (Digene Diagnostics, Gaithersburg, Maryland); 2, second-generation Hybrid Capture test (HC-2); and 3, polymerase chain reaction (PCR).
  
  
  RESULTS
  Nineteen patients (5.3%) had histologic CIN 2/3. The sensitivity and specificity of the repeat Pap smear alone for the detection of CIN 2/3 were 73.7% and 62.9%, respectively, when referring all women with a repeat Pap smear using an ASCUS-positive threshold. The proportion of women referred for colposcopy was 39.0%. When HPV testing for high risk was used for identification of women with histologic CIN 2/3, sensitivity and specificity were, respectively, 68.4% and 85.9% for HC-1, 89.5% and 73.9% for HC-2 and 89.5% and 59.0% for PCR. The rate of referral for colposcopy of these three modes of HPV testing was 16.9%, 29.4% and 44.0%, respectively. The sensitivity and specificity for identification of women with concomitant CIN 2/3 using a combination of repeat cytology showing a low grade squamous intraepithelial lesion or high grade squamous intraepithelial lesion and/or a test positive for high-oncogenic-risk HPV group were, respectively, 94.7% and 73.2% when used in combination with HC-2. The referral rate of women for colposcopy of this combined strategy was 30.4%.
  
  
  CONCLUSIONS
  As compared to the strategy using abnormal repeat Pap smear alone, those using high-risk HPV testing with Hybrid Capture showed statistically significantly higher specificities and lower proportions of women with ASCUS referred for colposcopy. In particular, a promising strategy would be to refer for colposcopy only women with repeat Pap smears showing squamous intraepithelial lesion and/or those positive for high-risk HPV detected by Hybrid Capture testing.
authors.affiliation: Departments of Pathology, Social and Preventive Medicine, and of Gynecology and Obstetrics, Laval University, Quebec, Canada. dspmoric@cha.quebec.qc.ca
authors.forename: C
authors.initials: C
authors.lastname: Morin
authors.forename: I
authors.initials: I
authors.lastname: Bairati
authors.forename: C
authors.initials: C
authors.lastname: Bouchard
authors.forename: M
authors.initials: M
authors.lastname: Fortier
authors.forename: M
authors.initials: M
authors.lastname: Roy
authors.forename: L
authors.initials: L
authors.lastname: Moore
authors.forename: A
authors.initials: A
authors.lastname: Meisels
mesh_terms: D000293:Adolescent; D000328:Adult; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D016022:Case-Control Studies; D003127:Colposcopy; D004279:DNA, Viral / Q000032:analysis*; D005260:Female; D006801:Humans; D008875:Middle Aged; D065006:Papanicolaou Test; D027383:Papillomaviridae / Q000235:genetics / Q000302:isolation & purification; D016133:Polymerase Chain Reaction / Q000592:standards; D011237:Predictive Value of Tests; D012680:Sensitivity and Specificity; D002583:Uterine Cervical Neoplasms / Q000473:pathology* / Q000821:virology; D014626:Vaginal Smears / Q000592:standards*; D002578:Uterine Cervical Dysplasia / Q000473:pathology* / Q000821:virology
chemical_list: D004279:DNA, Viral