title: Primary cervical cancer screening with human papillomavirus: end of study results from the ATHENA study using HPV as the first-line screening test.
abstract: OBJECTIVE
  ATHENA evaluated the cobas HPV Test as the primary screen for cervical cancer in women ≥25years. This reports the 3-year end-of-study results comparing the performance of HPV primary screening to different screening and triage combinations.
  
  
  METHODS
  42,209 women ≥25years were enrolled and had cytology and hrHPV testing. Women with abnormal cytology (≥atypical squamous cells of undetermined significance) and those HPV positive were referred to colposcopy. Women not reaching the study endpoint of CIN2+ entered the 3-year follow-up phase.
  
  
  RESULTS
  3-year CIR of CIN3+ in cytology-negative women was 0.8% (95% CI; 0.5-1.1%), 0.3% (95% CI 0.1-0.7%) in HPV-negative women, and 0.3% (95% CI; 0.1-0.6%) in cytology and HPV negative women. The sensitivity for CIN3+ of cytology was 47.8% (95% CI; 41.6-54.1%) compared to 61.7% (95% CI; 56.0-67.5%) for the hybrid strategy (cytology if 25-29years and cotesting with cytology and HPV if ≥30years) and 76.1% (95% CI; 70.3-81.8%) for HPV primary. The specificity for CIN3+ was 97.1% (95% CI; 96.9-97.2%), 94.6% (95% CI; 94.4-94.8%), and 93.5% (95% CI; 93.3-93.8%) for cytology, hybrid strategy, and HPV primary, respectively. Although HPV primary detects significantly more cases of CIN3+ in women ≥25years than either cytology or hybrid strategy, it requires significantly more colposcopies. However, the number of colposcopies required to detect a single CIN3+ is the same as for the hybrid strategy.
  
  
  CONCLUSIONS
  HPV primary screening in women ≥25years is as effective as a hybrid screening strategy that uses cytology if 25-29years and cotesting if ≥30years. However, HPV primary screening requires less screening tests.
authors.affiliation: Department of Pathology and Cell Biology, Columbia University, New York, NY, USA. Electronic address: tcw1@cumc.columbia.edu.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Wright
authors.affiliation: Department of Pathology, University of Virginia, Charlottesville, VA, USA. Electronic address: mhs2e@virginia.edu.
authors.forename: Mark H
authors.initials: MH
authors.lastname: Stoler
authors.affiliation: Roche Molecular Systems, Pleasanton, CA, USA. Electronic address: catherine_m.behrens@roche.com.
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Behrens
authors.affiliation: Roche Molecular Systems, Pleasanton, CA, USA. Electronic address: abha.sharma@roche.com.
authors.forename: Abha
authors.initials: A
authors.lastname: Sharma
authors.affiliation: Roche Molecular Systems, Pleasanton, CA, USA. Electronic address: guili.zhang@roche.com.
authors.forename: Guili
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Genentech, South San Francisco, CA, USA. Electronic address: wright.teresa@gene.com.
authors.forename: Teresa L
authors.initials: TL
authors.lastname: Wright
mesh_terms: D000328:Adult; D055088:Early Detection of Cancer; D005260:Female; D006801:Humans; D008403:Mass Screening / Q000379:methods*; D027383:Papillomaviridae / Q000235:genetics / Q000302:isolation & purification*; D030361:Papillomavirus Infections / Q000175:diagnosis* / Q000821:virology; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis / Q000473:pathology / Q000821:virology*; D014626:Vaginal Smears; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis / Q000473:pathology / Q000821:virology*
keywords: Cervical cancer screening; Cervical cytology; HPV