Abstract：
Human papillomavirus associated anogenital cancers are a significant global burden. The detection of biomarkers (circulating tumour DNA; ctDNA or circulating HPV DNA; cHPV DNA) in blood referred to as \"liquid biopsy\" may support the early diagnosis and monitoring of affected individuals.
A systematic review, including meta-analysis of studies available in the literature on the utilization of ctDNA and cHPV DNA as diagnostic, predictive, and monitoring biomarker tests of HPV associated anogenital cancers was performed following the criteria of PRISMA.
A total of 31 studies were eligible for systematic review; 20 used cHPV DNA in cervical cancers; 7 used ctDNA in cervical cancer; 5 used cHPV DNA in anal cancer; no eligible studies on vulva, vaginal or penile cancer were available. The meta-analysis identified low sensitivity (0.36) and high specificity (0.96) of cHPV DNA as diagnostic for cervical cancer. Comparatively, there was high sensitivity (0.95) and specificity (1.0) of cHPV DNA for the diagnosis of anal cancer. cHPV DNA and/or ctDNA in cervical cancer were prognostic markers associated with poor clinical outcomes. Additionally, in anal cancer the post treatment detection of cHPV DNA was informative in the prediction of treatment response or progression-free survival.
ctDNA and cHPV DNA are promising diagnostic and prognostic biomarkers for the detection of anogenital disease. Evolution and refinement of molecular tools is likely to improve performance further. Additionally the comparative absence of studies in the vulval, vaginal and penile context warrants further exploration and research.
A systematic review, including meta-analysis of studies available in the literature on the utilization of ctDNA and cHPV DNA as diagnostic, predictive, and monitoring biomarker tests of HPV associated anogenital cancers was performed following the criteria of PRISMA.
A total of 31 studies were eligible for systematic review; 20 used cHPV DNA in cervical cancers; 7 used ctDNA in cervical cancer; 5 used cHPV DNA in anal cancer; no eligible studies on vulva, vaginal or penile cancer were available. The meta-analysis identified low sensitivity (0.36) and high specificity (0.96) of cHPV DNA as diagnostic for cervical cancer. Comparatively, there was high sensitivity (0.95) and specificity (1.0) of cHPV DNA for the diagnosis of anal cancer. cHPV DNA and/or ctDNA in cervical cancer were prognostic markers associated with poor clinical outcomes. Additionally, in anal cancer the post treatment detection of cHPV DNA was informative in the prediction of treatment response or progression-free survival.
ctDNA and cHPV DNA are promising diagnostic and prognostic biomarkers for the detection of anogenital disease. Evolution and refinement of molecular tools is likely to improve performance further. Additionally the comparative absence of studies in the vulval, vaginal and penile context warrants further exploration and research.
摘要：
背景：人乳头瘤病毒相关的肛门生殖器癌症是一个巨大的全球负担。血液中生物标志物（循环肿瘤DNA;ctDNA或循环HPVDNA;cHPVDNA）的检测称为“液体活检”，可能支持早期诊断和监测受影响的个体。
方法：系统综述，包括文献中关于利用ctDNA和cHPVDNA作为诊断的研究的荟萃分析，预测性，按照PRISMA标准进行HPV相关肛门生殖器癌的生物标志物监测试验.
结果：共有31项研究符合系统评价的条件；20项在宫颈癌中使用cHPVDNA；7项在宫颈癌中使用ctDNA；5项在肛门癌中使用cHPVDNA；没有关于外阴的合格研究，有阴道癌或阴茎癌。荟萃分析确定cHPVDNA的低敏感性（0.36）和高特异性（0.96）可诊断宫颈癌。相对而言,cHPVDNA对肛门癌的诊断具有较高的敏感性（0.95）和特异性（1.0）。宫颈癌中cHPVDNA和/或ctDNA是与不良临床结局相关的预后标志物。此外,在肛门癌中,cHPVDNA的治疗后检测对于预测治疗反应或无进展生存期具有重要意义.
结论：ctDNA和cHPVDNA是检测肛门生殖器疾病的有希望的诊断和预后生物标志物。分子工具的进化和完善可能会进一步提高性能。此外，在外阴的研究比较缺乏，阴道和阴茎背景值得进一步探索和研究。
方法：系统综述，包括文献中关于利用ctDNA和cHPVDNA作为诊断的研究的荟萃分析，预测性，按照PRISMA标准进行HPV相关肛门生殖器癌的生物标志物监测试验.
结果：共有31项研究符合系统评价的条件；20项在宫颈癌中使用cHPVDNA；7项在宫颈癌中使用ctDNA；5项在肛门癌中使用cHPVDNA；没有关于外阴的合格研究，有阴道癌或阴茎癌。荟萃分析确定cHPVDNA的低敏感性（0.36）和高特异性（0.96）可诊断宫颈癌。相对而言,cHPVDNA对肛门癌的诊断具有较高的敏感性（0.95）和特异性（1.0）。宫颈癌中cHPVDNA和/或ctDNA是与不良临床结局相关的预后标志物。此外,在肛门癌中,cHPVDNA的治疗后检测对于预测治疗反应或无进展生存期具有重要意义.
结论：ctDNA和cHPVDNA是检测肛门生殖器疾病的有希望的诊断和预后生物标志物。分子工具的进化和完善可能会进一步提高性能。此外，在外阴的研究比较缺乏，阴道和阴茎背景值得进一步探索和研究。
