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Novel biomarkers with promising benefits for diagnosis of cervical neoplasia: a systematic review
Infectious Agents and Cancer ( IF 3.1 ) Pub Date : 2020-11-16 , DOI: 10.1186/s13027-020-00335-2
Calleb George Onyango , Lilian Ogonda , Bernard Guyah , Clement Shiluli , Gregory Ganda , Omenge Elkanah Orang’o , Kirtika Patel

Background Cervical cancer screening is slowly transitioning from Pappanicolaou cytologic screening to primary Visual Inspection with Acetic Acid (VIA) or HPV testing as an effort to enhance early detection and treatment. However, an effective triage tests needed to decide who among the VIA or HPV positive women should receive further diagnostic evaluation to avoid unnecessary colposcopy referrals is still lacking. Evidence from experimental studies have shown potential usefulness of Squamous Cell Carcinoma Antigen (SCC Ag), Macrophage Colony Stimulating Factor (M-CSF), Vascular Endothelial Growth Factor (VEGF), MicroRNA, p16INKa / ki-67, HPV E6/E7/mRNA, and DNA methylation biomarkers in detecting premalignant cervical neoplasia. Given the variation in performance, and scanty review studies in this field, this systematic review described the diagnostic performance of some selected assays to detect high-grade cervical intraepithelial neoplasia (CIN2+) with histology as gold standard. Methods We systematically searched articles published in English between 2012 and 2020 using key words from PubMed/Medline and SCOPUS with two reviewers assessing study eligibility, and risk of bias. We performed a descriptive presentation of the performance of each of the selected assays for the detection of CIN2 + . Results Out of 298 citations retrieved, 58 articles were included. Participants with cervical histology yielded CIN2+ proportion range of 13.7–88.4%. The diagnostic performance of the assays to detect CIN2+ was; 1) SCC-Ag: range sensitivity of 78.6–81.2%, specificity 74–100%. 2) M-CSF: sensitivity of 68–87.7%, specificity 64.7–94% 3) VEGF: sensitivity of 56–83.5%, specificity 74.6–96%. 4) MicroRNA: sensitivity of 52.9–67.3%, specificity 76.4–94.4%. 5) p16INKa / ki-67: sensitivity of 50–100%, specificity 39–90.4%. 6) HPV E6/E7/mRNA: sensitivity of 65–100%, specificity 42.7–90.2%, and 7) DNA methylation: sensitivity of 59.7–92.9%, specificity 67–98%. Conclusion Overall, the reported test performance and the receiving operating characteristics curves implies that implementation of p16ink4a/ki-67 assay as a triage for HPV positive women to be used at one visit with subsequent cryotherapy treatment is feasible. For the rest of assays, more robust clinical translation studies with larger consecutive cohorts of women participants is recommended.

中文翻译:

对宫颈瘤形成诊断具有潜在益处的新型生物标志物:系统评价

背景 宫颈癌筛查正在缓慢地从巴氏细胞学筛查转变为使用乙酸 (VIA) 或 HPV 检测的初步视觉检查,以努力加强早期检测和治疗。然而,仍然缺乏有效的分类测试来决定 VIA 或 HPV 阳性女性中的哪些人应该接受进一步的诊断评估以避免不必要的阴道镜转诊。实验研究的证据表明鳞状细胞癌抗原 (SCC Ag)、巨噬细胞集落刺激因子 (M-CSF)、血管内皮生长因子 (VEGF)、MicroRNA、p16INKa / ki-67、HPV E6/E7/mRNA 的潜在用途和 DNA 甲基化生物标志物用于检测宫颈癌前病变。鉴于表现的变化,以及该领域的评论研究很少,该系统评价描述了一些选定的检测方法的诊断性能,以检测以组织学为金标准的高级别宫颈上皮内瘤变 (CIN2+)。方法 我们使用来自 PubMed/Medline 和 SCOPUS 的关键词系统地检索了 2012 年至 2020 年间发表的英文文章,两名评审员评估了研究的资格和偏倚风险。我们对每个选定的 CIN2 + 检测方法的性能进行了描述性介绍。结果 在检索到的 298 篇引文中,包括 58 篇文章。宫颈组织学参与者的 CIN2+ 比例范围为 13.7-88.4%。检测 CIN2+ 的检测的诊断性能是:1) SCC-Ag:范围灵敏度为 78.6-81.2%,特异性为 74-100%。2) M-CSF:敏感性为 68-87.7%,特异性为 64.7-94% 3) VEGF:敏感性为 56-83.5%,特异性为 74.6-96%。4) MicroRNA:灵敏度52.9-67.3%,特异性76.4-94.4%。5) p16INKa / ki-67:灵敏度为 50-100%,特异性为 39-90.4%。6) HPV E6/E7/mRNA:敏感性为 65-100%,特异性为 42.7-90.2%,和 7) DNA 甲基化:敏感性为 59.7-92.9%,特异性为 67-98%。结论 总体而言,报告的测试性能和接收操作特性曲线表明,将 p16ink4a/ki-67 检测作为 HPV 阳性女性的分诊实施,在一次就诊时进行后续冷冻治疗是可行的。对于其余的检测,建议对更大的女性参与者连续队列进行更稳健的临床转化研究。特异性 39–90.4%。6) HPV E6/E7/mRNA:敏感性为 65-100%,特异性为 42.7-90.2%,和 7) DNA 甲基化:敏感性为 59.7-92.9%,特异性为 67-98%。结论 总体而言,报告的测试性能和接收操作特性曲线表明,将 p16ink4a/ki-67 检测作为 HPV 阳性女性的分诊实施,在一次就诊时进行后续冷冻治疗是可行的。对于其余的检测,建议对更大的女性参与者连续队列进行更稳健的临床转化研究。特异性 39–90.4%。6) HPV E6/E7/mRNA:敏感性为 65-100%,特异性为 42.7-90.2%,和 7) DNA 甲基化:敏感性为 59.7-92.9%,特异性为 67-98%。结论 总体而言,报告的测试性能和接收操作特性曲线表明,将 p16ink4a/ki-67 检测作为 HPV 阳性女性的分诊实施,在一次就诊时进行后续冷冻治疗是可行的。对于其余的检测,建议对更大的连续女性参与者队列进行更稳健的临床转化研究。报告的测试性能和接收操作特性曲线表明,将 p16ink4a/ki-67 检测作为一种对 HPV 阳性女性进行分流的方法,在一次就诊时进行后续冷冻治疗是可行的。对于其余的检测,建议对更大的女性参与者连续队列进行更稳健的临床转化研究。报告的测试性能和接收操作特性曲线表明,将 p16ink4a/ki-67 检测作为一种对 HPV 阳性女性进行分流的方法,在一次就诊时进行后续冷冻治疗是可行的。对于其余的检测,建议对更大的女性参与者连续队列进行更稳健的临床转化研究。
更新日期:2020-11-16
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