A comparison of the clinical utility of p16INK4a immunolocalization with the presence of human papillomavirus by hybrid capture 2 for the detection of cervical dysplasia/neoplasia

Abstract

BACKGROUND. Evidence suggests that overexpression of p16INK4a protein indicates infection and genomic integration of high‐risk human papillomavirus (HR HPV) and predicts progression to cervical high‐grade squamous intraepithelial lesions (HSILs) and carcinoma. The authors compared the ability of p16INK4a and HR HPV detection by Hybrid Capture 2 (HC2) to detect the presence of significant cervical disease. METHODS. Four hundred ThinPrep® specimens (100 each in 4 categories: 100 specimens that were negative for intraepithelial lesions, 100 specimens of atypical squamous cells of undetermined significance [ASC‐US], 100 specimens of low‐grade squamous intraepithelial lesions [LSILs], and 100 specimens of HSILs) were analyzed. p16INK4a protein was immunolocalized using a specific monoclonal antibody, and the detection of HR HPV in all 400 specimens was determined using HC2. RESULTS. p16INK4a was found to be positive in 78% of HSIL specimens, 42% of LSIL specimens, and 36% of ASC‐US specimens; whereas HC2 was positive in 92% of HSIL specimens, 81% of LSIL specimens, and 45% of ASC‐US specimens. In the HSIL category, the sensitivity, which was calculated using Grade 2 or greater cervical intraepithelial neoplasia as the endpoint, was 78% (50 of 66 specimens) for p16INK4a and 91% (60 of 66 specimens) for HC2. For LSIL, the sensitivity was 75% (3 of 4 specimens) for p16INK4a and 100% (4 of 4 specimens) for HC2. In the ASC‐US category, the sensitivity was 89% (8 of 9 specimens) for p16INK4a and 100% (9 of 9 specimens) for HC2. Overall, the sensitivity for HSIL was 92% for HC2 and 78% for p16INK4a. The specificity for HC2 was 8.3% for HSIL, 16.9% for LSIL, and 48.7% for ASC‐US; whereas the specificity for p16INK4a was 25% in HSIL, 59.1% in LSIL, and 68.4% in ASC‐US. The overall specificity was 25% for HC2 and 56% for p16INK4a. CONCLUSIONS. Although both p16INK4a and HC2 may aid in the clinical management of patients with clinically significant lesions, HC2 was found to have greater sensitivity, and p16INK4a greater specificity. The labeling of normal cells and bacteria may preclude the use of p16INK4a in automated screening or nonmorphologic assays. Cancer (Cancer Cytopathol) 2006. © 2006 American Cancer Society.

Expression of p16 in Sinonasal Undifferentiated Carcinoma (SNUC) Without Associated Human Papillomavirus (HPV)

“…Evidence suggests that overexpression of the p16 INK4A protein indicates infection with and genomic integration of high-risk HPV [28]. Despite overexpression of p16, HPV-infected cells continue to proliferate because Rb, the target of p16 inhibitory activity, is inactivated by the E7 HPV oncoprotein [29].…”

“…Despite overexpression of p16, HPV-infected cells continue to proliferate because Rb, the target of p16 inhibitory activity, is inactivated by the E7 HPV oncoprotein [29]. Therefore, p16 has been used as a predictor of cervical high-grade squamous intraepithelial lesions and carcinoma due to HPV-induced cell cycle dysregulation [28].…”

Comparison of p16INK4a and ProEx™ C immunostaining on cervical ThinPrep® cytology and biopsy specimens

“…Two potential explanations for this include an ability to ignore stained basal or focal staining of metaplastic cells on the tissue but not on cytology and/or deficiencies in the ThinPrep methodology used for this study. A study by Holladay et al 15 also expressed concern regarding truly negative cells demonstrating p16 staining.…”

p16/ki‐67 dual‐stain cytology in the triage of ASCUS and LSIL Papanicolaou cytology

“…[1][2][3][4][5][6][7][8] In the majority of the studies, p16 cytology was found to provide sensitivity rates for the detection of underlying high-grade cervical intraepithelial neoplasia (CIN of grade 2 or higher, CIN2þ), which were similar or slightly lower compared with the sensitivity of testing for the presence of human papillomavirus (HPV) infections. 7,9,10,11 At the same time, specificity of p16 cytology-based testing was found to be substantially higher than the specificity of HPV testing in all studies.…”