title: Triage of women with ASCUS and LSIL on Pap smear reports: management by repeat Pap smear, HPV DNA testing, or colposcopy?
abstract: BACKGROUND
  The purpose of this study was to determine the efficacy of a repeat Papanicolaou (Pap) smear and the Hybrid Capture tube-based (HCT) HPV DNA test for detecting cervical intraepithelial neoplasia (CIN) grade 2 or 3 in women with recent atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous intraepithelial lesion (LSIL) Pap smear reports.
  
  
  METHODS
  Women with a recent Pap smear report of ASCUS (n = 169) or LSIL (n = 110) had a repeat Pap smear, sampling of the cervix for HCT HPV DNA assay and a colposcopy examination. Data were evaluated using three different triage thresholds for colposcopy examination: a repeat Pap smear of persistent ASCUS or more severe dysplasia, a finding of persistent LSIL or more severe dysplasia, and a carcinogenic HPV test result.
  
  
  RESULTS
  The sensitivity, specificity, and positive and negative predictive values for detecting CIN 2/3 were 70%, 45%, 7%, and 96% for a repeat Pap smear using an ASCUS-positive threshold and 20%, 86%, 8%, and 94% for a repeat Pap smear using an LSIL-positive threshold, respectively, when women with an initial ASCUS Pap smear were considered. HPV testing for carcinogenic viruses alone or in combination with a repeat Pap smear (using ASCUS as a positive threshold) yielded results of 50%, 67%, 9%, and 96%, respectively, and 70%, 37%, 7%, and 95%, respectively, for detecting CIN 2/3. In women with an initial LSIL Pap smear, respective values for detecting CIN 2/3 by a repeat Pap smear with an ASCUS threshold were 92%, 26%, 14%, and 96%, and for an LSIL threshold 23%, 64%, 8%, and 86%, respectively. Hybrid Capture HPV testing alone or in combination with a repeat Pap smear yielded 69%, 43%, 14%, and 91%, respectively, and 100%, 21%, 14%, and 100%, respectively.
  
  
  CONCLUSIONS
  A Pap smear triage threshold restricted to LSIL or more severe dysplasia for women with prior ASCUS or LSIL Pap smear results was clearly ineffective for detecting high-grade cervical precancerous lesions. In contrast, when the repeat Pap smear triage threshold was expanded to include persistent ASCUS as abnormal, 83% of the women with CIN 2/3 were detected. Detection of carcinogenic HPV DNA using the HCT test was almost as sensitive for detecting CIN 2/3 as a solitary repeat Pap smear using an ASCUS or more severe positive threshold. Combining the HPV test with a repeat Pap smear did not significantly improve the sensitivity of cytology for detecting high-grade CIN. This study suggests that women with ASCUS and particularly LSIL Pap smears should be referred for a colposcopy examination until better triage methods become available.
authors.affiliation: Department of Family Medicine, Medical College of Georgia, Augusta 30912, USA.
authors.forename: D G
authors.initials: DG
authors.lastname: Ferris
authors.forename: T C
authors.initials: TC
authors.lastname: Wright
authors.forename: M S
authors.initials: MS
authors.lastname: Litaker
authors.forename: R M
authors.initials: RM
authors.lastname: Richart
authors.forename: A T
authors.initials: AT
authors.lastname: Lorincz
authors.forename: X W
authors.initials: XW
authors.lastname: Sun
authors.forename: L
authors.initials: L
authors.lastname: Borgatta
authors.forename: H
authors.initials: H
authors.lastname: Buck
authors.forename: L
authors.initials: L
authors.lastname: Kramer
authors.forename: R
authors.initials: R
authors.lastname: Rubin
mesh_terms: D000328:Adult; D003127:Colposcopy; D015344:DNA Probes, HPV; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D006801:Humans; D065006:Papanicolaou Test; D027383:Papillomaviridae / Q000235:genetics; D012680:Sensitivity and Specificity; D014218:Triage; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis* / Q000821:virology; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000821:virology; D014626:Vaginal Smears
chemical_list: D015344:DNA Probes, HPV; D004279:DNA, Viral