21 - Biomarker P16 Predicts Progression Risk of Anal Low-grade Squamous Intraepithelial Lesions

Abstract

Background To determine whether biomarker P16INK4a predicts progression risk for anal low-grade squamous intraepithelial lesions (LSIL). Methods 109 HIV-infected and 18 HIV-uninfected patients with biopsy-proven anal LSIL at initial screening underwent surveillance high-resolution anoscopy and biopsy within two years of diagnosis. P16 immunohistochemistry (IHC) was performed on index lesions and evaluated using a semi-quantitative scoring system. The association of predictors and lesional outcomes (progression, persistence, or regression) was analyzed using ordinal logistic regression models. A subset of p16-positive lesions was tested for high-risk human papillomavirus (HR-HPV) DNA using Real-time PCR. Results Upon follow-up, 46 (36%) LSILs progressed to HSIL, 50 (39%) persisted as LSIL, and 31 (24%) regressed to benign mucosa (median 16 months, range 2–24). Age, gender, race, history of condylomata, CD4+ T-cell count, and HIV plasma viral load were similar regardless of clinical outcome. P16 immunoreactivity of index lesion was classified as block-positive (n=36), focal-positive (n=49), or negative (n=42). 64% of block-positive lesions progressed, as opposed to 35% of focal-positive and 14% of negative lesions (p Conclusions Biomarker p16 is the strongest predictor for anal LSIL-to-HSIL progression, outperforming other risk factors. To enhance the overall effectiveness of surveillance, we propose using p16 IHC to help stratify patients at high versus low risk of progression.