Clinical Utility of Reflex Testing with Cancer Biomarkers to Improve Diagnostic Accuracy of Primary Human Papillomavirus Screening.
Clinical Utility of Reflex Testing with Cancer Biomarkers to Improve Diagnostic Accuracy of Primary Human Papillomavirus Screening.
复制标题
用癌症生物标志物进行反射测试的临床实用性，以提高原发性人乳头瘤病毒筛查的诊断准确性。
DOI：
10.1158/1055-9965.epi-21-0972
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发表时间：
2022-03-01
期刊：
影响因子：
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通讯作者：
Kuhn L
中科院分区：
文献类型：
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作者：
Johnson LG;Saidu R;Svanholm-Barrie C;Boa R;Moodley J;Tergas A;Persing D;Campbell SA;Tsai WY;Wright TC;Denny L;Kuhn L
HPV检测是宫颈癌筛查的基石，具有突出的敏感性，但只有中等特异性。我们评估了癌症生物标志物的反射测试是否改善了筛查的灵敏度/特异性平衡。采集南非开普敦30-65岁女性的宫颈样本，采用Xpert HPV和实时PCR检测细胞周期蛋白依赖性激酶抑制剂2A（CDKN 2A）、拓扑异构酶2 α（TOP 2A）和Ki 67（MKi 67）的mRNA。纳入了经组织学证实的宫颈上皮内瘤变2级或更严重（CIN 2+）的女性（85名女性无HIV，166名女性有HIV）和无宫颈疾病的女性（331名无HIV，257名女性有HIV）。当用于阳性HPV结果后的反射测试时，生物标志物可以很好地区分有和没有CIN 2+的女性。包含CDKN 2A和MKi 67两者具有最好的性能，在没有和具有HIV的女性中的曲线下面积（AUC）分别为0.9171和0.8734。虽然这些性能参数非常好，但与仅使用具有更严格的循环阈值截止值的HPV检测和HPV基因型选择的方法相比，这些性能参数并没有改善，HPV基因型选择在无HIV和有HIV的女性中分别达到0.9059和0.8705的AUC。生物标志物可在HPV阳性结果后用作分诊，但在选定的高风险基因型上使用更高的病毒载量截止值的方法并不优于该方法。单独使用HPV检测的筛查方法可以更容易地在护理点实施。
HPV testing is the cornerstone of cervical cancer screening with outstanding sensitivity but only moderate specificity. We evaluated whether reflex testing for cancer biomarkers improves the sensitivity/specificity balance of screening. Cervical samples from women in Cape Town, South Africa, aged 30–65 years, were collected and tested with Xpert HPV and with real-time PCR to detect mRNA for Cyclin-Dependent Kinase Inhibitor 2A (CDKN2A), Topoisomerase 2 alpha (TOP2A) and Ki67 (MKi67). Women with histologically-confirmed cervical intraepithelial neoplasia grade 2 or worse (CIN2+) (85 women without and 166 with HIV) and women with no cervical disease (331 without and 257 with HIV) were included. When used as reflex tests after a positive HPV result, biomarkers discriminated well between women with and without CIN2+. The inclusion of both CDKN2A and MKi67 had the best performance with area under the curve (AUC) of 0.9171 and 0.8734 in women without and with HIV, respectively. While excellent, these performance parameters did not improve on an approach utilizing only HPV testing with more stringent cycle threshold cut-offs and HPV genotype selection which achieved AUC of 0.9059 and 0.8705 in women without and with HIV, respectively. Biomarkers can be used as triage after positive HPV results but do not out-perform an approach utilizing higher viral load cut-offs on selected high-risk genotypes. A screening approach using HPV testing alone can be more easily implemented at the point-of-care.