PDF(Pubmed)
Abstract：
OBJECTIVE: WHO recommends human papillomavirus (HPV) testing for cervical screening, with triage of high-risk HPV (hrHPV) positive women. However, there are limitations to effective triage for low-resource, high-burden settings, such as Papua New Guinea. In this exploratory study, we assessed the performance of host methylation as triage tools for predicting high-grade squamous intraepithelial lesions (HSIL) in self-collected and clinician-collected samples.
METHODS: Exploratory observational study.
METHODS: Provincial hospital, same-day cervical screen-and-treat trial, Papua New Guinea.
METHODS: 44 hrHPV+women, with paired self/clinician-collected samples (4 squamous cell carcinomas (SCC), 19 HSIL, 4 low-grade squamous intraepithelial lesions, 17 normal).
METHODS: Methylation levels of CADM1, MAL and miR124-2 analysed by methylation-specific PCRs against the clinical endpoint of HSIL or SCC (HSIL+) measured using liquid-based-cytology/p16-Ki67 stain.
RESULTS: In clinician-collected samples, MAL and miR124-2 methylation levels were significantly higher with increasing grade of disease (p=0.0046 and p<0.0015, respectively). miR124-2 was the best predictor of HSIL (area under the curve, AUC 0.819) while MAL of SCC (AUC 0.856). In self-collected samples, MAL best predicted HSIL (AUC 0.595) while miR124-2 SCC (AUC 0.812). Combined miR124-2/MAL methylation yielded sensitivity and specificity for HSIL+ of 90.5% (95% CI 69.6% to 98.8%) and 70% (95% CI 45.7% to 88.1%), respectively, in clinician-collected samples, and 81.8% (95% CI 59.7% to 94.8%) and 47.6% (95% CI 25.7% to 70.2%), respectively, in self-collected samples. miR124-2/MAL plus HPV16/HPV18 improved sensitivity for HSIL+ (95.2%, 95% CI 76.2% to 99.9%) but decreased specificity (55.0%, 95% CI 31.5% to 76.9%).
CONCLUSIONS: miR124-2/MAL methylation is a potential triage strategy for the detection of HSIL/SCC in low-income and middle-income country.
METHODS: Exploratory observational study.
METHODS: Provincial hospital, same-day cervical screen-and-treat trial, Papua New Guinea.
METHODS: 44 hrHPV+women, with paired self/clinician-collected samples (4 squamous cell carcinomas (SCC), 19 HSIL, 4 low-grade squamous intraepithelial lesions, 17 normal).
METHODS: Methylation levels of CADM1, MAL and miR124-2 analysed by methylation-specific PCRs against the clinical endpoint of HSIL or SCC (HSIL+) measured using liquid-based-cytology/p16-Ki67 stain.
RESULTS: In clinician-collected samples, MAL and miR124-2 methylation levels were significantly higher with increasing grade of disease (p=0.0046 and p<0.0015, respectively). miR124-2 was the best predictor of HSIL (area under the curve, AUC 0.819) while MAL of SCC (AUC 0.856). In self-collected samples, MAL best predicted HSIL (AUC 0.595) while miR124-2 SCC (AUC 0.812). Combined miR124-2/MAL methylation yielded sensitivity and specificity for HSIL+ of 90.5% (95% CI 69.6% to 98.8%) and 70% (95% CI 45.7% to 88.1%), respectively, in clinician-collected samples, and 81.8% (95% CI 59.7% to 94.8%) and 47.6% (95% CI 25.7% to 70.2%), respectively, in self-collected samples. miR124-2/MAL plus HPV16/HPV18 improved sensitivity for HSIL+ (95.2%, 95% CI 76.2% to 99.9%) but decreased specificity (55.0%, 95% CI 31.5% to 76.9%).
CONCLUSIONS: miR124-2/MAL methylation is a potential triage strategy for the detection of HSIL/SCC in low-income and middle-income country.
摘要：
目的：WHO推荐人乳头瘤病毒（HPV）检测用于宫颈筛查，对高危型HPV（hrHPV）阳性女性进行分诊。然而,对低资源的有效分类存在局限性，高负担设置，比如巴布亚新几内亚。在这项探索性研究中，我们评估了在自我收集和临床医生收集的样本中,宿主甲基化作为预测高级别鳞状上皮内病变(HSIL)的分诊工具的性能.
方法：探索性观察研究。
方法：省立医院，当天的宫颈筛查和治疗试验，巴布亚新几内亚。
方法：44hrHPV+女性，与配对的自我/临床医生收集的样本（4个鳞状细胞癌（SCC），19HSIL,4低度鳞状上皮内病变，17正常）。
方法：通过甲基化特异性PCR分析CADM1、MAL和miR124-2的甲基化水平与使用液基细胞学/p16-Ki67染色测量的HSIL或SCC(HSIL+)的临床终点。
结果：在临床医生收集的样本中，随着疾病等级的增加，MAL和miR124-2甲基化水平显着升高（分别为p=0.0046和p<0.0015）。miR124-2是HSIL的最佳预测因子(曲线下面积，AUC0.819），而SCC的MAL（AUC0.856）。在自我收集的样本中，MAL最佳预测HSIL(AUC0.595)而miR124-2SCC(AUC0.812)。联合miR124-2/MAL甲基化对HSIL+的敏感性和特异性分别为90.5%（95%CI69.6%至98.8%）和70%（95%CI45.7%至88.1%），分别,在临床医生收集的样本中，和81.8%(95%CI59.7%至94.8%)和47.6%(95%CI25.7%至70.2%)，分别,在自我收集的样本中。miR124-2/MAL加HPV16/HPV18提高了HSIL+的灵敏度(95.2%,95%CI76.2%至99.9%），但特异性降低（55.0%，95%CI31.5%至76.9%）。
结论：miR124-2/MAL甲基化是低收入和中等收入国家检测HSIL/SCC的潜在分类策略。
方法：探索性观察研究。
方法：省立医院，当天的宫颈筛查和治疗试验，巴布亚新几内亚。
方法：44hrHPV+女性，与配对的自我/临床医生收集的样本（4个鳞状细胞癌（SCC），19HSIL,4低度鳞状上皮内病变，17正常）。
方法：通过甲基化特异性PCR分析CADM1、MAL和miR124-2的甲基化水平与使用液基细胞学/p16-Ki67染色测量的HSIL或SCC(HSIL+)的临床终点。
结果：在临床医生收集的样本中，随着疾病等级的增加，MAL和miR124-2甲基化水平显着升高（分别为p=0.0046和p<0.0015）。miR124-2是HSIL的最佳预测因子(曲线下面积，AUC0.819），而SCC的MAL（AUC0.856）。在自我收集的样本中，MAL最佳预测HSIL(AUC0.595)而miR124-2SCC(AUC0.812)。联合miR124-2/MAL甲基化对HSIL+的敏感性和特异性分别为90.5%（95%CI69.6%至98.8%）和70%（95%CI45.7%至88.1%），分别,在临床医生收集的样本中，和81.8%(95%CI59.7%至94.8%)和47.6%(95%CI25.7%至70.2%)，分别,在自我收集的样本中。miR124-2/MAL加HPV16/HPV18提高了HSIL+的灵敏度(95.2%,95%CI76.2%至99.9%），但特异性降低（55.0%，95%CI31.5%至76.9%）。
结论：miR124-2/MAL甲基化是低收入和中等收入国家检测HSIL/SCC的潜在分类策略。
