PCDHGB7 hypermethylation-based Cervical cancer Methylation (CerMe) detection for the triage of high-risk human papillomavirus-positive women: a prospective cohort study
Dan Cao,
Zhicong Yang,
Shihua Dong,
Yuhong Li,
Zhanrui Mao,
Qi Lu,
Peng Xu,
Minfang Shao,
Lei Pan,
Xu Han,
Jiangjing Yuan,
Qiong Fan,
Lei Chen,
Yanzhong Wang,
Weipei Zhu,
Wenqiang Yu,
Yudong Wang
Affiliations
Dan Cao
Department of Gynecology, The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai Key Laboratory of Embryo Original Diseases
Zhicong Yang
Shanghai Public Health Clinical Center and Department of General Surgery, Huashan Hospital, Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University
Shihua Dong
Shanghai Public Health Clinical Center and Department of General Surgery, Huashan Hospital, Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University
Yuhong Li
Department of Gynecology, The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai Key Laboratory of Embryo Original Diseases
Zhanrui Mao
Shanghai Public Health Clinical Center and Department of General Surgery, Huashan Hospital, Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University
Qi Lu
Department of Obstetrics and Gynecology, Jinshan Hospital of Fudan University
Peng Xu
Shanghai Public Health Clinical Center and Department of General Surgery, Huashan Hospital, Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University
Minfang Shao
Department of Obstetrics and Gynecology, 2nd Affiliated Hospital of Soochow University
Lei Pan
Department of Gynecology, The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai Key Laboratory of Embryo Original Diseases
Xu Han
Department of Gynecology, The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai Key Laboratory of Embryo Original Diseases
Jiangjing Yuan
Department of Gynecology, The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai Key Laboratory of Embryo Original Diseases
Qiong Fan
Department of Gynecology, The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai Key Laboratory of Embryo Original Diseases
Lei Chen
Department of Gynecology, The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai Key Laboratory of Embryo Original Diseases
Yanzhong Wang
Department of Population Health Sciences, School of Life Course and Population Sciences, King’s College London
Weipei Zhu
Department of Obstetrics and Gynecology, 2nd Affiliated Hospital of Soochow University
Wenqiang Yu
Shanghai Public Health Clinical Center and Department of General Surgery, Huashan Hospital, Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University
Yudong Wang
Department of Gynecology, The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai Key Laboratory of Embryo Original Diseases
Abstract Background Implementation of high-risk human papillomavirus (hrHPV) screening has greatly reduced the incidence and mortality of cervical cancer. However, a triage strategy that is effective, noninvasive, and independent from the subjective interpretation of pathologists is urgently required to decrease unnecessary colposcopy referrals in hrHPV-positive women. Methods A total of 3251 hrHPV-positive women aged 30–82 years (median = 41 years) from International Peace Maternity and Child Health Hospital were included in the training set (n = 2116) and the validation set (n = 1135) to establish Cervical cancer Methylation (CerMe) detection. The performance of CerMe as a triage for hrHPV-positive women was evaluated. Results CerMe detection efficiently distinguished cervical intraepithelial neoplasia grade 2 or worse (CIN2 +) from cervical intraepithelial neoplasia grade 1 or normal (CIN1 −) women with excellent sensitivity of 82.4% (95% CI = 72.6 ~ 89.8%) and specificity of 91.1% (95% CI = 89.2 ~ 92.7%). Importantly, CerMe showed improved specificity (92.1% vs. 74.9%) in other 12 hrHPV type-positive women as well as superior sensitivity (80.8% vs. 61.5%) and specificity (88.9% vs. 75.3%) in HPV16/18 type-positive women compared with cytology testing. CerMe performed well in the triage of hrHPV-positive women with ASC-US (sensitivity = 74.4%, specificity = 87.5%) or LSIL cytology (sensitivity = 84.4%, specificity = 83.9%). Conclusions PCDHGB7 hypermethylation-based CerMe detection can be used as a triage strategy for hrHPV-positive women to reduce unnecessary over-referrals. Trial registration ChiCTR2100048972. Registered on 19 July 2021.
