Varga Norbert, Mózes Johanna, Keegan Helen, White Christine, Kelly Lynne, Pilkington Loretto, Benczik Márta, Zsuzsanna Schaff, Sobel Gábor, Koiss Róbert, Babarczi Edit, Nyíri Miklos, Kovács Laura, Attila Sebe, Kaltenecker Borbála, Géresi Adrienn, Kocsis Adrienn, O'Leary John, Martin Cara M, Jeney Csaba
CellCall Ltd, Röppentyű utca 48, Budapest, 1134, Hungary.
Department of Histopathology, School of Medicine, Trinity College Dublin, Dublin, Ireland.
Pathol Oncol Res. 2017 Apr;23(2):295-305. doi: 10.1007/s12253-016-0094-1. Epub 2016 Aug 6.
In the era of primary vaccination against HPV and at the beginning of the low prevalence of cervical lesions, introduction of screening methods that can distinguish between low- and high-grade lesions is necessary in order to maintain the positive predictive value of screening. This case-control study included 562 women who attended cervical screening or were referred for colposcopy and 140 disease free controls, confirmed by histology and/or cytology. The cases were stratified by age. Using routine exfoliated liquid based cytological samples RT-PCR measurements of biomarker genes, high-risk HPV testing and liquid based cytology were performed and used to evaluate different testing protocols including sets of genes/tests with different test cut-offs for the diagnostic panels. Three new panels of cellular biomarkers for improved triage of hrHPV positive women (diagnostic panel) and for prognostic assessment of CIN lesions were proposed. The diagnostic panel (PIK3AP1, TP63 and DSG3) has the potential to distinguish cytologically normal hrHPV+ women from hrHPV+ women with CIN2+. The prognostic gene panels (KRT78, MUC5AC, BPIFB1 and CXCL13, TP63, DSG3) have the ability to differentiate hrHPV+ CIN1 and carcinoma cases. The diagnostic triage panel showed good likelihood ratios for all age groups. The panel showed age-unrelated performance and even better diagnostic value under age 30, a unique feature among the established cervical triage tests. The prognostic gene-panels demonstrated good discriminatory power and oncogenic, anti-oncogenic grouping of genes. The study highlights the potential for the gene expression panels to be used for diagnostic triage and lesion prognostics in cervical cancer screening.
在HPV初次疫苗接种时代以及宫颈病变低流行率开始之际，为维持筛查的阳性预测值，引入能够区分低级别和高级别病变的筛查方法很有必要。这项病例对照研究纳入了562名接受宫颈筛查或被转诊进行阴道镜检查的女性以及140名经组织学和/或细胞学证实无疾病的对照者。病例按年龄分层。利用常规脱落液基细胞学样本对生物标志物基因进行RT-PCR检测，进行高危型HPV检测和液基细胞学检查，并用于评估不同的检测方案，包括针对诊断组具有不同检测临界值的基因/检测组合。提出了三组新的细胞生物标志物，用于改善高危型HPV阳性女性的分流（诊断组）以及CIN病变的预后评估。诊断组（PIK3AP1、TP63和DSG3）有潜力将细胞学正常的高危型HPV阳性女性与CIN2+的高危型HPV阳性女性区分开来。预后基因组（KRT78、MUC5AC、BPIFB1和CXCL13、TP63、DSG3）有能力区分高危型HPV阳性的CIN1和癌病例。诊断分流组在所有年龄组中均显示出良好的似然比。该组显示出与年龄无关的性能，在30岁以下时诊断价值甚至更好，这是现有宫颈分流检测中独一无二的特征。预后基因组显示出良好的鉴别能力以及基因的致癌、抗癌分组。该研究突出了基因表达组在宫颈癌筛查中用于诊断分流和病变预后评估的潜力。
