Bouchilloux S, Fer F, Lemée F, Barradeau S, Dvorak V, Kubickova S, Ventruba P, Tachezy R, Trnková M, Janda P, Abscheidt J, Annibal E, El Mhali D, Garcia F, Kech M, Pilger G, Bensimon A, Mahé F
Ceska Gynekol. 2019 Winter;84(2):84-92.
The aim of the EXPL-HPV-002 study is to evaluate the integration of 14 high-risk HPV as a biomarker of the severity and the progression of cervical lesions. Such a „triage biomarker“ would help to reduce the number of unnecessary colposcopies, to avoid over-treatment of lesions that spontaneously regress and to better target the lesions requiring treatment.
EXPL-HPV-002 is a prospective, open-label, single arm, GCP study conducted at 2 clinical sites in the Czech Republic.
Investigations centers: Private Gynecology Center, Brno; Gynecological and Obstetrical Clinic, Brno; Genotyping central lab: NRL for Papillomaviruses and polyomaviruses, IHBT, Prague; Histology Central reading: Aeskulab Pathology, Prague; Molecular combing HPV test: Genomic Vision, Bagneux.
From June 2016 to May 2018, 688 patients aged 25-65, referred to colposcopy after an abnormal Pap-smear, were enrolled in the study. Among them 60% were found HPV high-risk. The study is divided in two phases: 1. a cross-sectional phase using data collected at first visit (colposcopy images ± histology, pap-smear for HPV genotyping and molecular combing) to study the association between HPV integration status versus colposcopy and histology grades; 2. a longitudinal phase using data collected in follow-up visits: cytology at 6, 18 and 30 months and colposcopy ± histology at 12, 24 and 36 months. A pap-smear collected at 12, 24 and 36 months allows to perform genotyping and molecular combing. HPV integration status is analyzed in comparison with the evolution of lesions, viral clearance and HPV genotype. HPV genotyping and molecular combing were performed on pap-smear samples in central laboratories. Histology data were reviewed by central reading.
The transversal phase of the study is achieved and shows that the HPV integration into the human DNA, monitored by molecular combing, can significantly differentiate normal subjects from women with cervical lesions or cancer.
HPV integration into the host genome, monitored by Genomic Visions technology, is a reliable diagnostic biomarker that will greatly help clinicians to improve their medical decision tree.
EXPL-HPV-002研究的目的是评估14种高危型人乳头瘤病毒（HPV）整合情况作为宫颈病变严重程度和进展的生物标志物。这样一种“分流生物标志物”将有助于减少不必要的阴道镜检查次数，避免对自发消退的病变进行过度治疗，并更好地针对需要治疗的病变。
EXPL-HPV-002是一项在捷克共和国2个临床地点进行的前瞻性、开放标签、单臂、药物临床试验规范（GCP）研究。
研究中心：布尔诺私立妇科中心；布尔诺妇产科诊所；基因分型中心实验室：布拉格IHBT的乳头瘤病毒和多瘤病毒国家参考实验室（NRL）；组织学中央阅片：布拉格Aeskulab病理学；分子梳状HPV检测：巴涅的Genomic Vision。
2016年6月至2018年5月，688名年龄在25至65岁之间、巴氏涂片异常后转诊至阴道镜检查的患者被纳入研究。其中60%被发现为高危型HPV。该研究分为两个阶段：1. 横断面阶段，使用首次就诊时收集的数据（阴道镜图像±组织学、用于HPV基因分型和分子梳状分析的巴氏涂片）研究HPV整合状态与阴道镜和组织学分级之间的关联；2. 纵向阶段，使用随访时收集的数据：6个月、18个月和30个月时的细胞学检查，以及12个月、24个月和36个月时的阴道镜检查±组织学检查。在12个月、24个月和36个月时收集的巴氏涂片可用于进行基因分型和分子梳状分析。将HPV整合状态与病变演变、病毒清除和HPV基因型进行比较分析。HPV基因分型和分子梳状分析在中央实验室对巴氏涂片样本进行。组织学数据由中央阅片进行审查。
该研究的横断面阶段已完成，结果表明，通过分子梳状分析监测的HPV整合入人类DNA情况，可显著区分正常受试者与宫颈病变或癌症患者。
通过Genomic Vision技术监测的HPV整合入宿主基因组情况，是一种可靠的诊断生物标志物，将极大地帮助临床医生改进其医疗决策流程。
