Utility of gene methylation analysis, cytological examination, and HPV-16/18 genotyping in triage of high-risk human papilloma virus-positive women

• Published in: Oncotarget 2017-09, Vol.8 (37), p.62274-62285
• Main Authors: Tian, Yan, Yuan Wu, Na-Yi, Liou, Yu-Ligh, Yeh, Ching-Tung, Cao, Lanqin, Kang, Ya-Nan, Wang, Huei-Jen, Li, Yichen, Chu, Tang-Yuan, Li, Wei, Liu, Xiang, Zhang, Yi, Zhou, Honghao, Zhang, Yu
• Format: Article
• Language: English
• Subjects: Research Paper
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.19459

In 2015, the American Society for Colposcopy and Cervical Pathology and the Society of Gynecologic Oncology issued interim guidance for the use of a human papillomavirus (HPV) test for primary screening, suggesting triage of women positive for high-risk human papillomavirus (hrHPV) by HPV-16/18 genotyping and cytology for women positive for non-16/18 hrHPV. The design of the present study was based on this interim guidance and analysis of the methylation status of specific candidate genes, which has been proposed as a tool to reduce unnecessary referral following primary HPV screening for cervical cancer. We performed a hospital-based case-control study including 312 hrHPV-positive women. hrHPV genotyping was performed by nested multiplex PCR assay with type-specific primers.Residual cervical cells from liquid-based cytology were used for extraction of genomic DNA for assessment of the methylation status of , , , and and HPV genotyping. Combined with HPV-16/18 genotyping, both a dual methylation test for / and testing for methylation demonstrated 100% association of methylation with pathology results, indicating carcinoma or squamous cell carcinoma. The sensitivity and specificity of the dual methylation test for / as a reflex test for identification of CIN3+ lesions were 78.85% and 73.55% (odds ratio = 10.37, 95% confidence interval = 4.76-22.58), respectively. This strategy could reduce the number of patients referred for colposcopic examination by 31.3% compared with cytology, and thus provide a feasible follow-up solution in regions where colposcopy is not readily available. This strategy could also prevent unnecessary anxiety in women with hrHPV infection.