Histological grading of squamous intraepithelial lesions or intraepithelial neoplasia is fundamental for clinical management and for assessment of the risk of progression. Biomarkers are important for assisting correct grading of these lesions, reducing inter and intraobserver variability and most promising, for prognosis. Although p16 is the most studied biomarker in this setting, there are several other biomarkers that have been studied, reflecting also the need to find a better single or association option that can be more suitable, especially for classification purposes. A PubMed and Embase search was conducted from their inception until April 2018, aiming to identify biomarkers evaluated in histological samples of anal squamous intraepithelial lesions, other than p16. Information on "Ki-67", "ProExTM C", "p53", "human papillomavirus L1 capsid protein", "stathmin-1", "minichromosome maintenance protein", "p21", "proliferating cell nuclear antigen", "histones", "human papillomavirus E4", "chromosomal abnormalities" and "methylation" was collected and reviewed. From these, the most studied biomarker was by far Ki-67. In many cases there were few studies performed for each biomarker, with no clear standardized interpretation of the immunostaining. An increased positive rate with more severe grades of lesions was shown in many cases. Prognostic data are limited and need to be further validated.

中文翻译：

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除p16免疫染色之外：肛门鳞状上皮内病变的生物标志物概述。

鳞状上皮内病变或上皮内瘤形成的组织学分级是临床管理和评估进展风险的基础。生物标志物对于协助正确分类这些病变，降低观察者之间和观察者之间的变异性以及最有希望的预后至关重要。尽管在这种情况下p16是研究最多的生物标志物，但已经研究了其他几种生物标志物，这也反映出需要寻找更好的单一或关联选项，尤其是用于分类的目的。从研究开始到2018年4月，进行了PubMed和Embase搜索，旨在鉴定在肛门鳞状上皮内病变（p16除外）的组织学样本中评估的生物标志物。有关“ Ki-67”，“ ProExTM C”，“ p53”，“人乳头瘤病毒L1衣壳蛋白”，“ stathmin-1”，“微染色体维持蛋白”，“ p21”，“增殖细胞核抗原”，“组蛋白”，“人乳头瘤病毒E4”，“染色体异常”和“甲基化”为收集并审查。从这些，到目前为止，研究最多的生物标志物是Ki-67。在许多情况下，对每种生物标记物进行的研究很少，而对免疫染色没有明确的标准化解释。在许多情况下，显示出更高的阳性率，病灶更严重。预后数据有限，需要进一步验证。对免疫染色没有明确的标准化解释。在许多情况下，显示出更高的阳性率，病灶更严重。预后数据有限，需要进一步验证。对免疫染色没有明确的标准化解释。在许多情况下，显示出更高的阳性率，病灶更严重。预后数据有限，需要进一步验证。