The utility of p16Ink4a in discriminating between cervical intraepithelial neoplasia 1 and nonneoplastic equivocal lesions of the cervix

Rachel Redman, Irina Rufforny, Chen Liu, Edward J. Wilkinson, Nicole A. Massoll

Research output: Contribution to journalArticlepeer-review

34 Scopus citations


Context. - The protein p16Ink4a is overexpressed in cervical lesions associated with high-risk human papillomavirus (HPV) subtypes 16 and 18, but not in low-risk HPV subtypes 6 and 11 or non-HPV-associated cervical lesions. Objective. - To determine whether p16Ink4a expression in equivocal cervical lesions helps distinguish atypical non-HPV changes from HPV-related changes. Design. - One hundred ninety-one cervical lesions, including 81 cervical intraepithelial neoplasia 1,52 squamous metaplasia, 33 cellular features suggestive of HPV-related change, 9 reserve cell hyperplasia, 4 microglandular hyperplasia, and 12 inflammatory cervicitis, were randomly selected from archival cervical biopsy specimens. All 191 samples were studied with p16Ink4a (JC8 monoclonal antibody). Reactivity for p16 Ink4a was scored on a 3-tier system as follows: negative, 0% to 5% cells reactive; focal/scattered positive, greater than 5% and less than or equal to 80% cells reactive; diffuse positive, greater than 80% cells reactive. Reactivity was based on normal/reactive cervical specimens where anti-p16 antibody was negative/weakly expressed in non-cervical epithelial cells. Cervical intraepithelial neoplasia 1 lesions not reactive for p16 Ink4a were investigated for the presence of high-risk HPV by real-time polymerase chain reaction. Results. - No p16Ink4a reactivity was detected in the cervical lesions associated with atypical non-HPV change. Eleven of the cervical intraepithelial neoplasia 1 lesions showed focal/scattered reactivity expression for p16Ink4a, and 19 of the CIN 1 lesions had diffuse reactivity. Fifty of 51 of the CIN 1 lesions negative for p16Ink4a were real-time polymerase chain reaction negative for the presence of high-risk HPV; 1 was real-time polymerase chain reaction positive for high-risk HPV. Conclusions. - The data support the routine use of p16 Ink4a immunohistochemical evaluation of cervical biopsy specimens for better discrimination of non-HPV-associated lesions from HPV-related lesions.

Original languageEnglish (US)
Pages (from-to)795-799
Number of pages5
JournalArchives of Pathology and Laboratory Medicine
Issue number5
StatePublished - May 2008
Externally publishedYes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Medical Laboratory Technology


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