Wormald Benjamin, Rodriguez-Manzano Jesus, Moser Nicolas, Pennisi Ivana, Ind Thomas E J, Vroobel Katherine, Attygalle Ayoma, Georgiou Pantelis, deSouza Nandita M
Cancer Research UK Cancer Imaging Centre, Division of Radiotherapy and Imaging, The Institute of Cancer Research, London, United Kingdom.
Department of Infectious Disease, Faculty of Medicine, Imperial College, London, United Kingdom.
Front Oncol. 2021 Nov 1;11:747614. doi: 10.3389/fonc.2021.747614. eCollection 2021.
To establish the sensitivity and specificity of a human papillomavirus (HPV) and tumor marker DNA/mRNA assay for detecting cervical cancer that is transferrable to a Lab-on-a-chip platform and determine its diagnostic benefit in early stage disease when used in conjunction with high-resolution endovaginal magnetic resonance imaging (MRI).
Forty-one patients (27 with Stage1 cervical cancer [Group1] and 14 non-cancer HPV negative controls [Group2]) had DNA and RNA extracted from cervical cytology swab samples. HPV16, HPV18, hTERT, TERC/GAPDH and MYC/GAPDH concentration was established using a loop mediated isothermal amplification (LAMP) assay. Thresholds for tumor marker detection for Group1 were set from Group2 analysis (any hTERT, TERC/GAPDH 3.12, MYC/GAPDH 0.155). Group 1 participants underwent endovaginal MRI. Sensitivity and specificity for cancer detection by LAMP and MRI individually and combined was documented by comparison to pathology.
Sensitivity and specificity for cancer detection was 68.8% and 77.8% if any tumor marker was positive regardless of HPV status (scenario1), and 93.8% and 55.8% if tumor marker or HPV were positive (scenario 2). Adding endovaginal MRI improved specificity to 88.9% in scenario 1 (sensitivity 68.8%) and to 77.8%% in scenario2 (sensitivity 93.8%).
Specificity for cervical cancer detection using a LAMP assay is superior with tumor markers; low sensitivity is improved by HPV detection. Accuracy for early stage cervical cancer detection is optimal using a spatially multiplexed tumor marker/HPV LAMP assay together with endovaginal MRI.
建立一种可转移至芯片实验室平台的人乳头瘤病毒（HPV）和肿瘤标志物DNA/mRNA检测方法用于检测宫颈癌的敏感性和特异性，并确定其与高分辨率阴道内磁共振成像（MRI）联合使用时在早期疾病中的诊断价值。
41例患者（27例I期宫颈癌患者[第1组]和14例非癌HPV阴性对照者[第2组]）的宫颈细胞学拭子样本提取DNA和RNA。采用环介导等温扩增（LAMP）法测定HPV16、HPV18、hTERT、TERC/GAPDH和MYC/GAPDH浓度。根据第2组分析结果设定第1组肿瘤标志物检测阈值（任何hTERT、TERC/GAPDH＞3.12、MYC/GAPDH＞0.155）。第1组参与者接受阴道内MRI检查。通过与病理结果比较，记录LAMP和MRI单独及联合检测癌症的敏感性和特异性。
无论HPV状态如何，若任何肿瘤标志物呈阳性，则检测癌症的敏感性和特异性分别为68.8%和77.8%（情况1）；若肿瘤标志物或HPV呈阳性，则敏感性和特异性分别为93.8%和55.8%（情况2）。增加阴道内MRI检查后，情况1中的特异性提高到88.9%（敏感性68.8%），情况2中的特异性提高到77.8%（敏感性93.8%）。
使用LAMP法检测宫颈癌的特异性在肿瘤标志物方面更优；HPV检测可提高低敏感性。使用空间多重肿瘤标志物/HPV LAMP检测法联合阴道内MRI对早期宫颈癌进行检测的准确性最佳。
