Using P16 Immunohistochemistry to Classify Morphologic Cervical Intraepithelial Neoplasia 2: Correlation of Ambiguous Staining Patterns with HPV Subtypes and Clinical Outcome

Publication date: Available online 11 July 2017
Source:Human Pathology
Author(s): Yuxin Liu, Mahfood Alqatari, Kieran Sultan, Fei Ye, Dana Gao, Keith Sigel, David Zhang, Tamara Kalir
P16INK4a immunohistochemistry (IHC) is widely used to facilitate the diagnosis of human papillomavirus (HPV)-associated cervical precancerous lesions. While most p16 results are distinctly positive or negative, certain ones are ambiguous: they meet some but not all requirements for the “block-positive” pattern. It is unclear whether ambiguous p16 immunoreactivity indicates oncogenic HPV infection or risk of progression. Herein, we compared HPV genotypes and subsequent High-grade Squamous Intraepithelial Lesion (HSIL) outcomes among 220 cervical biopsies with a differential diagnosis of Cervical Intraepithelial Neoplasia 2 (CIN 2) based on hematoxylin and eosin morphology and varying degrees of p16 immunoreactivity. P16 results were classified as block-positive (n=40, 18%), negative (n=130, 59%), or ambiguous (n=50, 23%), a category we further grouped into three patterns: strong/basal (n=18), strong/focal (n=15), and weak/diffuse (n=17). 70% of ambiguous p16 lesions were negative for the most common low- and high-risk HPV types; the remaining 30% were positive for HPV 16, 18, 45, 58, 59, or 66. Three patterns revealed comparably low HPV detection rates (28%, 27% and 35%). During 12-month surveillance, HSILs were detected in 35% of the p16 block-positive group, 1.5% of negative group, and 16% of the ambiguous group. The accuracy of ambiguous p16 immunoreactivity in predicting oncogenic HPV and HSIL outcome is significantly lower than that of the block-positive pattern but greater than negative staining. Specific guidelines for this intermediate category should prevent diagnostic errors and help implement p16 IHC in general practice.


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