肛癌预防有两个关键点：某些群体的发病率要高几倍，如艾滋病病毒感染者和同性恋者，同时也没有一个明确的筛查指南。本系统评价评估了DNA HRHPV（高危型人乳头瘤病毒）、mRNA HPV、DNA HPV16分离和p16染色标记物在肛管刮片中鉴定肛管上皮内瘤变（AIN）2级或3级（总称为肛高级鳞状上皮内病变，aHSIL）和癌症方面的准确性。我们在MEDLINE、Cochrane图书馆、Embase电子数据库以及灰色文献中搜索了符合条件的文章，截止日期为2022年7月31日。本系统评价和荟萃分析纳入了比较生物标志物检测与高分辨直肠镜检查（HRA）后的组织病理学检查作为参考标准的观察性研究。我们（ACM，TF）分析了男女病患使用DNA HRHPV、mRNA HPV、DNA HPV16和/或p16生物标志物进行肛癌筛查的研究。分析是成对进行的，例如AIN2级或更严重（AIN2+）与AIN1级、HPV感染与正常（AIN1-）之间。PROSPERO CRD42015024201。我们纳入了21个研究，共7445名病患。DNA HR HPV显示出较高的敏感性92.4%（95% CI 84.2-96.5），特异性41.7%（95% CI 33.9-44.9）和AUC 0.67，其次是mRNA HPV检测，敏感性为77.3%（95% CI 73.2-80.9），特异性为61.9%（95% CI 56.6-66.9）和AUC 0.78。DNA HPV16显示出较高的特异性71.7%（95% CI 55.3-83.8），p16检测的特异性为64.1%（95% CI 51.0-75.4）；DNA HPV16的敏感性为53.3%（95% CI 35.4-70.3），AUC为0.69，而p16的敏感性为68.8%（95% CI 47.9-84.1），AUC为0.74。在包含13个研究和5123名病患的HIV感染男性同性恋者亚组分析中，准确性相似，敏感性稍高，特异性稍低。考虑总体研究间变异的度量，mRNA HPV检测显示出最小的95%预测椭圆面积，为6.0%，受低logit敏感性的影响，0.011。其他所有测试组的椭圆面积均超过50%，表示高度异质性。我们的发现表明，如果后续使用具有较高特异性的生物标志物，DNA HR HPV可以成为筛查aHSIL和肛癌的有用工具。作为一个独立的测试，mRNA HPV具有更好的性能。本研究没有资金来源。© 2023 The Author(s).

Anal cancer prevention has two critical points: the incidence rate is several fold higher for some groups, such as people living with human immunodeficiency virus (HIV) and men who have sex with men (MSM), and there is not a well-defined guideline for its screening. This systematic review evaluates the accuracy of DNA HRHPV (high-risk human papillomavirus), mRNA HPV, DNA HPV16 isolated and p16 staining biomarkers in anal canal smears for identifying anal intraepithelial neoplasia (AIN) 2 or 3, summarised as anal high-grade squamous intraepithelial lesions (aHSIL), and cancer.We searched the MEDLINE, Cochrane Library and Embase electronic databases as well as Grey literature to identify eligible papers published up to 31st July 2022. This systematic review and meta-analysis included observational studies comparing biomarker tests to histopathology after HRA (High-resolution Anoscopy) as a reference standard. We (ACM, TF) analysed studies in which patients of both sexes were screened for anal cancer using DNA HRHPV, mRNA HPV, DNA HPV16 and/or p16 biomarkers. The analysis was performed in pairs, for instance AIN2 or worse (AIN2+) vs. AIN1, HPV infection and normal (AIN1-). PROSPERO CRD42015024201.We included 21 studies with 7445 patients. DNA HR HPV showed a higher sensitivity 92.4% (95% CI 84.2-96.5), specificity 41.7% (95% CI 33.9-44.9) and AUC 0.67, followed by the mRNA HPV test, with a sensitivity 77.3% (95% CI 73.2%-80.9%), specificity 61.9% (95% CI 56.6-66.9) and AUC 0.78. DNA HPV16 showed higher specificity 71.7% (95% CI 55.3-83.8), followed by p16 test, 64.1% (95% CI 51.0-75.4); Sensitivity of DNA HPV16 was 53.3% (95% CI 35.4-70.3) and AUC 0.69, while p16 had a sensitivity of 68.8% (95% CI 47.9-84.1) and AUC 0.74. Subgroup analysis of MSM with HIV, with 13 studies and 5123 patients, showed similar accuracy, with a bit higher sensitivities and lower specificities. Considering the measure of the total between-study variability, mRNA HPV tests showed the smallest area of the 95% prediction ellipse, 6.0%, influenced by the low logit sensitivity, 0.011. All other groups of tests exceed 50% prediction ellipse area, which represent a high heterogeneity.Our findings suggested that DNA HR HPV can be a useful tool for screening for aHSIL and anal cancer if followed by biomarker with a higher specificity. As an isolated test, mRNA HPV had better performance.There was no funding source for this study.© 2023 The Author(s).