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 journalArticle

19 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2932-2939
Number of pages8
JournalInternational Journal of Cancer
Volume138
Issue number12
DOIs
Publication statusPublished - Jun 15 2016

Fingerprint

Polymerase Chain Reaction
Early Detection of Cancer
Uterine Cervical Neoplasms
Histology
Genotype
Databases
Pathologists

Keywords

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

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Petry, K. U., Cox, J. T., Johnson, K., Quint, W., Ridder, R., Sideri, M., ... Behrens, C. M. (2016). Evaluating HPV-negative CIN2+ in the ATHENA trial. International Journal of Cancer, 138(12), 2932-2939. https://doi.org/10.1002/ijc.30032

Evaluating HPV-negative CIN2+ in the ATHENA trial. / Petry, Karl Ulrich; Cox, J. Thomas; Johnson, Kristin; Quint, Wim; Ridder, Ruediger; Sideri, Mario; Wright, Thomas C.; Behrens, Catherine M.

In: International Journal of Cancer, Vol. 138, No. 12, 15.06.2016, p. 2932-2939.

Research output: Contribution to journalArticle

Petry, KU, Cox, JT, Johnson, K, Quint, W, Ridder, R, Sideri, M, Wright, TC & Behrens, CM 2016, 'Evaluating HPV-negative CIN2+ in the ATHENA trial', International Journal of Cancer, vol. 138, no. 12, pp. 2932-2939. https://doi.org/10.1002/ijc.30032
Petry KU, Cox JT, Johnson K, Quint W, Ridder R, Sideri M et al. Evaluating HPV-negative CIN2+ in the ATHENA trial. International Journal of Cancer. 2016 Jun 15;138(12):2932-2939. https://doi.org/10.1002/ijc.30032
Petry, Karl Ulrich ; Cox, J. Thomas ; Johnson, Kristin ; Quint, Wim ; Ridder, Ruediger ; Sideri, Mario ; Wright, Thomas C. ; Behrens, Catherine M. / Evaluating HPV-negative CIN2+ in the ATHENA trial. In: International Journal of Cancer. 2016 ; Vol. 138, No. 12. pp. 2932-2939.
@article{c59121e6b6e142b4b1e3a2b367db5ef5,
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{\circledR} 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.",
keywords = "adenocarcinoma in situ, cervical cancer screening, cervical intraepithelial neoplasia, histology, HPV DNA testing, HPV genotype",
author = "Petry, {Karl Ulrich} and Cox, {J. Thomas} and Kristin Johnson and Wim Quint and Ruediger Ridder and Mario Sideri and Wright, {Thomas C.} and Behrens, {Catherine M.}",
year = "2016",
month = "6",
day = "15",
doi = "10.1002/ijc.30032",
language = "English",
volume = "138",
pages = "2932--2939",
journal = "International Journal of Cancer",
issn = "0020-7136",
publisher = "Wiley-Liss Inc.",
number = "12",

}

TY - JOUR

T1 - Evaluating HPV-negative CIN2+ in the ATHENA trial

AU - Petry, Karl Ulrich

AU - Cox, J. Thomas

AU - Johnson, Kristin

AU - Quint, Wim

AU - Ridder, Ruediger

AU - Sideri, Mario

AU - Wright, Thomas C.

AU - Behrens, Catherine M.

PY - 2016/6/15

Y1 - 2016/6/15

N2 - 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.

AB - 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.

KW - adenocarcinoma in situ

KW - cervical cancer screening

KW - cervical intraepithelial neoplasia

KW - histology

KW - HPV DNA testing

KW - HPV genotype

UR - http://www.scopus.com/inward/record.url?scp=84959564532&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84959564532&partnerID=8YFLogxK

U2 - 10.1002/ijc.30032

DO - 10.1002/ijc.30032

M3 - Article

C2 - 26851121

AN - SCOPUS:84959564532

VL - 138

SP - 2932

EP - 2939

JO - International Journal of Cancer

JF - International Journal of Cancer

SN - 0020-7136

IS - 12

ER -