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Infection with high-risk HPV types upregulates expression of p16 - a tumor suppressor gene. Immunostaining for p16 has become established as a reliable surrogate marker for HPV-induced lesions. It has a specificity of 98-99% and sensitivity of 100%.

It is reliable when performed on intraepithelial neoplasia or early invasive carcinomas. p16 expression may be lost in advanced cases. High-grade squamous intraepithelial lesions show diffuse, block-like staining (strong nuclear and cytoplasmic) as seen in the left half of this anal mucosa. Low-grade squamous intraepithelial lesions and reactive processes show absent, weak, or patchy staining for p16.

Image courtesy of: Ed Uthman, MD.

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