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  • Title: The utility of p16(Ink4a) in discriminating between cervical intraepithelial neoplasia 1 and nonneoplastic equivocal lesions of the cervix.
    Author: Redman R, Rufforny I, Liu C, Wilkinson EJ, Massoll NA.
    Journal: Arch Pathol Lab Med; 2008 May; 132(5):795-9. PubMed ID: 18466028.
    Abstract:
    CONTEXT: The protein p16(Ink4a) 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 p16(Ink4a) 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 p16(Ink4a) (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 p16(Ink4a) 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 p16(Ink4a), and 19 of the CIN 1 lesions had diffuse reactivity. Fifty of 51 of the CIN 1 lesions negative for p16(Ink4a) 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.
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