title: Evaluating HPV-negative CIN2+ in the ATHENA trial.
abstract: 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.
authors: Department of Obstetrics and Gynecology, Klinikum Wolfsburg, Wolfsburg, Germany.
authors: Karl Ulrich
authors: KU
authors: Petry
authors: Department of Health Services, University of California, Santa Barbara, CA.
authors: J Thomas
authors: JT
authors: Cox
authors: Roche Molecular Systems, Pleasanton, CA.
authors: Kristin
authors: K
authors: Johnson
authors: DDL Diagnostic Laboratory, Rijswijk, The Netherlands.
authors: Wim
authors: W
authors: Quint
authors: Ventana Medical Systems, Inc, Tucson, AZ.
authors: Ruediger
authors: R
authors: Ridder
authors: Mario
authors: M
authors: Sideri
authors: Department of Pathology and Cell Biology, Columbia University, New York, NY.
authors: Thomas C
authors: TC
authors: Wright
authors: Roche Molecular Systems, Pleasanton, CA.
authors: Catherine M
authors: CM
authors: Behrens
mesh_terms: D055088:Early Detection of Cancer; D005260:Female; D006801:Humans; D008403:Mass Screening; D060787:Neoplasm Grading; D030361:Papillomavirus Infections / Q000175:diagnosis; D014481:United States; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis*; D055815:Young Adult; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis*
keywords: HPV DNA testing; HPV genotype; adenocarcinoma in situ; cervical cancer screening; cervical intraepithelial neoplasia; histology