生物标志物 P16 预测肛门低级别鳞状上皮内病变的进展风险。
Biomarker P16 predicts progression risk of anal low-grade squamous intraepithelial lesions.
机构信息
Department of Pathology.
Division of General Internal Medicine, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York.
出版信息
AIDS. 2018 Oct 23;32(16):2309-2316. doi: 10.1097/QAD.0000000000001957.
OBJECTIVES
The aim of this study was to determine whether biomarker P16 predicts progression risk for anal low-grade squamous intraepithelial lesions (LSILs).
DESIGN
A retrospective study.
METHODS
One hundred and nine HIV-infected and 18 HIV-uninfected patients with biopsy-proven anal LSIL at initial screening underwent surveillance high-resolution anoscopy and biopsy within 2 years of diagnosis. P16 immunohistochemistry 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 analysed using ordinal logistic regression models. A subset of p16-positive LSILs was tested for high-risk human papillomavirus (HR-HPV) DNA using real-time PCR.
RESULTS
Upon follow-up, 46 (36%) LSILs progressed to high-grade squamous intraepithelial lesion (HSIL), 50 (40%) persisted as LSIL and 31 (24%) regressed to benign mucosa (median 16 months, range 5-24 months). Age, sex, 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). Sixty-four percent of block-positive lesions progressed, as opposed to 35% of focal-positive and 14% of negative lesions (P < 0.001). HR-HPV DNA was detected in 90% of p16 block-positive lesions vs. 55% of focal-positive lesions. In unadjusted analyses, positive p16, HIV and former smoker status were significantly associated with lesional persistence and progression. P16 remained the only significant predictor in an adjusted model.
CONCLUSION
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 immunohistochemistry to help stratify patients at high vs. low risk of progression.
目的
本研究旨在确定生物标志物 P16 是否可预测肛门低级别鳞状上皮内病变（LSIL）的进展风险。
设计
回顾性研究。
方法
109 例 HIV 感染和 18 例 HIV 未感染的初始筛查时经活检证实的肛门 LSIL 患者在诊断后 2 年内接受了监测高分辨率肛门镜检查和活检。对指数病变进行 P16 免疫组化染色，并使用半定量评分系统进行评估。使用有序逻辑回归模型分析预测因子与病变结局（进展、持续或消退）之间的关系。使用实时聚合酶链反应检测部分 p16 阳性 LSIL 中的高危型人乳头瘤病毒（HR-HPV）DNA。
结果
随访时，46 例（36%）LSIL 进展为高级别鳞状上皮内病变（HSIL），50 例（40%）持续为 LSIL，31 例（24%）消退为良性黏膜（中位时间为 16 个月，范围为 5-24 个月）。无论临床结局如何，年龄、性别、种族、湿疣病史、CD4 T 细胞计数和 HIV 血浆病毒载量均相似。指数病变的 P16 免疫反应性分为块状阳性（n=36）、局灶阳性（n=49）或阴性（n=42）。64%的块状阳性病变进展，而 35%的局灶阳性病变和 14%的阴性病变进展（P<0.001）。p16 块状阳性病变中检测到 HR-HPV DNA 的比例为 90%，而局灶阳性病变为 55%。在未调整分析中，p16 阳性、HIV 阳性和曾吸烟与病变持续存在和进展显著相关。在调整模型中，p16 仍然是唯一显著的预测因子。
结论
生物标志物 p16 是肛门 LSIL 向 HSIL 进展的最强预测因子，优于其他危险因素。为了提高监测的整体效果，我们建议使用 p16 免疫组化染色来帮助分层高风险和低风险进展的患者。
Zotero 插件