Utility of Human Papillomavirus Capsid Protein L1 and p16 in the Assessment and Accurate Classification of Anal Squamous Intraepithelial Lesions.

Abstract

Morphologic evaluation of anal dysplasia remains problematic, especially in cases with limited biopsy samples or obscuring inflammation. Studies in cervical neoplasia have shown that human papillomavirus (HPV) L1 capsid production is highest in low-grade squamous intraepithelial lesions (LSILs) and progressively decreases in high-grade squamous intraepithelial lesions (HSILs). The combined utility of HPV L1 and p16 expression in assessing anal squamous intraepithelial lesions (SILs) has never been analyzed and forms the basis of this study. In total, 145 anal lesions were reviewed and immunohistochemically stained for HPV L1 and p16. p16 expression was recorded as negative, patchy/focal, or diffuse. For analytical purposes, condylomas were evaluated separately from rest of the LSILs. There were 34 (23%) condylomas, 64 (44%) LSILs, and 47 (32%) HSILs. HPV L1 was significantly associated with condylomas (68%) and LSILs (52%) compared with HSILs (9%; P < .0001). Diffuse p16 staining was present only in HSILs (P < .0001), whereas a patchy/focal p16 staining pattern was observed in both LSILs and condylomas. HPV L1 and diffuse p16 expression is mutually exclusive in most anal SILs and helps separate LSIL and HSIL cases. Application of both HPV L1 and p16 can not only facilitate accurate grading but also contribute to risk assessment in anal neoplasia.