Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Multicenter Study
. 2016 Jun 15;138(12):2932-9.
doi: 10.1002/ijc.30032. Epub 2016 Mar 2.

Evaluating HPV-negative CIN2+ in the ATHENA trial

Karl Ulrich Petry  1 , J Thomas Cox  2 , Kristin Johnson  3 , Wim Quint  4 , Ruediger Ridder  5 , Mario Sideri, Thomas C Wright Jr  6 , Catherine M Behrens  3
Affiliations
Multicenter Study

Evaluating HPV-negative CIN2+ in the ATHENA trial

Karl Ulrich Petry et al. Int J Cancer. .

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.

Keywords: HPV DNA testing; HPV genotype; adenocarcinoma in situ; cervical cancer screening; cervical intraepithelial neoplasia; histology.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Overview of cobas‐negative CIN2 cases. aOne case with no slide available for review; bincluding coinfections.
Figure 2
Figure 2
Overview of cobas‐negative CIN3/ACIS cases. aOne case with no slide available for review; bincluding coinfections; cnot confirmed on re‐review.
See this image and copyright information in PMC

References

    1. Walboomers JM, Jacobs MV, Manos MM, et al. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol 1999;189:12–19. - PubMed
    1. Liebrich C, Brummer O, Von Wasielewski R, et al. Primary cervical cancer truly negative for high‐risk human papillomavirus is a rare but distinct entity that can affect virgins and young adolescents. Eur J Gynaecol Oncol 2009;30:45–8. - PubMed
    1. Böhmer G, van den Brule AJ, Brummer O, et al. No confirmed case of human papillomavirus DNA‐negative cervical intraepithelial neoplasia grade 3 or invasive primary cancer of the uterine cervix among 511 patients. Am J Obstet Gynecol 2003;189:118–20. - PubMed
    1. Holl K, Nowakowski AM, Powell N, et al. Human papillomavirus prevalence and type‐distribution in cervical glandular neoplasias: results from a European multinational epidemiological study. Int J Cancer 2015;137:2858–68. [Epub ahead of print] - PMC - PubMed
    1. Kurman RJ, Carcangiu ML, Herrington CS, et al., eds. WHO classification of tumors of female reproductive organs, 4th edn., vol. 6 Geneva: World Health Organization, 2014.

Publication types