Homerton Anal Neoplasia Service (HANS), Homerton University Hospital, London, UK.
Faculty of Medicine of the University of Porto, Porto, Portugal.
Mod Pathol. 2018 Jul;31(7):1026-1035. doi: 10.1038/s41379-018-0026-6. Epub 2018 Feb 13.
p16 is the most widely studied biomarker in lower anogenital tract squamous intraepithelial lesions and, currently the only recommended biomarker for histological grade assessment. The aim of this systematic review and meta-analysis was to evaluate p16-positive rates according to anal squamous intraepithelial lesions/anal intraepithelial neoplasia (AIN) grade. Two investigators independently searched four electronic databases: PubMed, Web of Sciences, Scopus, and Embase from inception until August 2017. Studies that evaluated p16 immunostaining in histological samples of anal and/or perianal squamous intraepithelial lesions and defined a p16-positive result as diffuse block staining with nuclear or nuclear plus cytoplasmic staining were included. A meta-analysis was performed using a random effects model. Fifteen studies consisting of 790 samples were included. The proportion of p16 expression increased with the severity of histological grade. p16 positivity was 2% (95% CI: 0.2-5%) in normal histology, 12% (95% CI: 2-27%) in low-grade squamous intraepithelial lesions (LSILs)/AIN1 (excluding condylomas), 7% (95% CI: 2-13%) in all LSIL (AIN1/LSIL/condyloma), 76% (95% CI: 61-88%) in AIN2, and 90% (95% CI: 82-95%) in AIN3. For anal high-grade squamous intraepithelial lesions (HSILs), in studies using a two-tiered nomenclature, p16 positivity was 84% (95% CI: 66-96%) and for all HSIL (AIN2, AIN3, HSIL combined) it was 82% (95% CI: 72-91%). In summary, p16 positivity in anal squamous intraepithelial lesions appears to be in a similar range to the commonly described cervical squamous intraepithelial lesions, however, for anal low-grade lesions positivity seems to be lower.
p16 是研究最广泛的下生殖道鳞状上皮内病变的生物标志物，也是目前唯一推荐用于组织学分级评估的生物标志物。本系统评价和荟萃分析的目的是根据肛门鳞状上皮内病变/肛门上皮内瘤变（AIN）分级评估 p16 阳性率。两名研究人员独立检索了四个电子数据库：PubMed、Web of Sciences、Scopus 和 Embase，检索时间从建库起至 2017 年 8 月。本研究纳入评估肛门和/或肛周鳞状上皮内病变组织学样本中 p16 免疫染色并将弥漫性块状核染色或核和细胞质染色阳性定义为 p16 阳性的研究。采用随机效应模型进行荟萃分析。共纳入 15 项研究，包含 790 例样本。组织学分级越严重，p16 表达的比例越高。p16 阳性率在正常组织学中为 2%（95%CI：0.2-5%），在低级别鳞状上皮内病变（LSILs）/AIN1（不包括湿疣）中为 12%（95%CI：2-27%），在所有 LSIL（AIN1/LSIL/湿疣）中为 7%（95%CI：2-13%），在 AIN2 中为 76%（95%CI：61-88%），在 AIN3 中为 90%（95%CI：82-95%）。对于肛门高级别鳞状上皮内病变（HSILs），在采用两阶梯命名法的研究中，p16 阳性率为 84%（95%CI：66-96%），而所有 HSIL（AIN2、AIN3、HSIL 合并）的 p16 阳性率为 82%（95%CI：72-91%）。总之，肛门鳞状上皮内病变中的 p16 阳性率与通常描述的宫颈鳞状上皮内病变相似，但肛门低级别病变的阳性率似乎较低。
