Evaluating HPV-negative CIN2+ in the ATHENA trial

Karl Ulrich Petry, J. Thomas Cox, Kristin Johnson, Wim Quint, Ruediger Ridder, Mario Sideri, Thomas C. Wright, Catherine M. Behrens

Research output: Contribution to journalArticlepeer-review


A post hoc analysis of the ATHENA study was performed to determine whether true HPV-negative cervical lesions occur and whether they have clinical relevance. The ATHENA database was searched for all CIN2 or worse (CIN2+) cases with cobas HPV-negative results and comparison was made with Linear Array (LA) and Amplicor to detect true false-negative HPV results. Immunostaining with p16 was performed on these cases to identify false-positive histology results. H&E slides were re-reviewed by the study pathologists with knowledge of patient age, HPV test results and p16 immunostaining. Those with positive p16 immunostaining and/or a positive histopathology review underwent whole tissue section HPV PCR by the SPF10/LiPA/RHA system. Among 46,887 eligible women, 497 cases of CIN2+ were detected, 55 of which tested negative by the cobas® HPV Test (32 CIN2, 23 CIN3/ACIS). By LA and/or Amplicor, 32 CIN2+ (20 CIN2, 12 CIN3/ACIS) were HPV positive and categorized as false-negatives by cobas HPV; nine of 12 false-negative CIN3/ACIS cases were p16+. There were 23 cases (12 CIN2, 11 CIN3/ACIS) negative by all HPV tests; seven of 11 CIN3/ACIS cases were p16+. H&E slides were available for six cases for re-review and all were confirmed as CIN3/ACIS. Tissue PCR was performed on the six confirmed CIN3/ACIS cases (and one without confirmation): four were positive for HPV types not considered oncogenic, two were positive for oncogenic genotypes and one was indeterminate. In summary, subanalysis of a large cervical cancer screening study did not identify any true CIN3/ACIS not attributable to HPV.

Original languageEnglish
Pages (from-to)2932-2939
Number of pages8
JournalInternational Journal of Cancer
Issue number12
Publication statusPublished - Jun 15 2016


  • adenocarcinoma in situ
  • cervical cancer screening
  • cervical intraepithelial neoplasia
  • histology
  • HPV DNA testing
  • HPV genotype

ASJC Scopus subject areas

  • Cancer Research
  • Oncology


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