title: Effects of age and human papilloma viral load on colposcopy triage: data from the randomized Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous Intraepithelial Lesion Triage Study (ALTS).
abstract: BACKGROUND
  Testing for oncogenic human papillomavirus (HPV) DNA at a 1.0-pg/mL threshold represents a promising approach for colposcopy triage of atypical squamous cells of undetermined significance (ASCUS), but not for low-grade squamous intraepithelial lesions (LSIL). Considering age or viral load could improve colposcopy triage.
  
  
  METHODS
  We determined the sensitivity for detecting Cervical Intraepithelial Neoplasia 3 (CIN3) and cancer and the percentage of referrals for colposcopy using HPV testing and repeat thin-layer cytopathology in 2198 women with ASCUS and in 848 women with LSIL enrolled in ALTS from November 1996 through December 1998. We analyzed results by age and at two thresholds for HPV load and repeat cytopathology.
  
  
  RESULTS
  For ASCUS, the overall sensitivity of HPV testing at 1.0 pg/mL was 96.1% (95% confidence interval [CI] = 92.8 to 99.5%) and varied minimally with age (range, 93.9% to 97.8%). HPV testing at this threshold would refer 31.2% (95% CI = 28.0% to 34.3%) of women aged 29 years or older as compared with more than 65% of younger women. Among women aged 29 years or older with ASCUS, referral for repeat cytopathology of ASCUS had a sensitivity of 90.9% (95% CI = 81.1% to 100.0%) and would refer 50.1% (95% CI = 46.7 to 53.5%). Among all ASCUS, HPV testing using a 10.0-pg/mL threshold decreased sensitivity to 91.5% and referrals to 41.7%. More than 63% of LSIL would have been referred using any strategy achieving 90% sensitivity.
  
  
  CONCLUSIONS
  For women with ASCUS, HPV testing was highly sensitive for detecting CIN3 and cancer with dramatically fewer referrals of older women. Neither a single HPV test nor repeat cytopathology provides useful triage for women with LSIL.
authors.affiliation: Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892-7374, USA. shermanm@mail.nih.gov
authors.forename: Mark E
authors.initials: ME
authors.lastname: Sherman
authors.forename: Mark
authors.initials: M
authors.lastname: Schiffman
authors.forename: J Thomas
authors.initials: JT
authors.lastname: Cox
mesh_terms: D000328:Adult; D000367:Age Factors; D002294:Carcinoma, Squamous Cell / Q000473:pathology* / Q000821:virology*; D003127:Colposcopy; D005260:Female; D006801:Humans; D027383:Papillomaviridae / Q000302:isolation & purification*; D030361:Papillomavirus Infections / Q000175:diagnosis* / Q000473:pathology; D012017:Referral and Consultation; D012680:Sensitivity and Specificity; D014412:Tumor Virus Infections / Q000175:diagnosis* / Q000473:pathology; D002583:Uterine Cervical Neoplasms / Q000473:pathology* / Q000821:virology*; D019562:Viral Load; D002578:Uterine Cervical Dysplasia / Q000473:pathology* / Q000821:virology*