Journal
BMC CANCER
Volume 15, Issue -, Pages -Publisher
BMC
DOI: 10.1186/s12885-015-1411-x
Keywords
Cervical cancer; DNA methylation; Biomarker; Self-collected; Physician-collected; Real-time quantitative methylation-specific polymerase chain reaction (QMSP)
Categories
Funding
- Tri-Service General Hospital [TSGH-C103-006-008-S01S02S03]
- Ministry of Science and Technology [NSC 102-2628-B-038-010-MY3, NSC 103-2325-B-195-002]
- Taipei Medical University [103TMU-SHH-11, TMUTOP103005-1]
- Teh-Tzer Study Group for Human Medical Research Foundation
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Background: Non-attendance at gynecological clinics is a major limitation of cervical cancer screening and self-collection of samples may improve this situation. Although HPV testing of self-collected vaginal samples is acceptable, the specificity is inadequate. The current focus is increasing self-collection of vaginal samples to minimize clinic visits. In this study, we analyzed the concordance and clinical performance of DNA methylation biomarker (PAX1, SOX1, and ZNF582) detection in self-collected vaginal samples and physician-collected cervical samples for the identification of cervical neoplasm. Methods: We enrolled 136 cases with paired methylation data identified from abnormal Pap smears (n = 126) and normal controls (n = 10) regardless of HPV status at gynecological clinics. The study group comprised 37 cervical intraepithelial neoplasm I (CIN1), 23 cervical intraepithelial neoplasm II (CIN2), 16 cervical intraepithelial neoplasm III (CIN3), 30 carcinoma in situ (CIS), 13 squamous cell carcinomas (SCCs) and seven adenocarcinomas (ACs)/adenosquamous carcinomas (ASCs). PAX1, SOX1 and ZNF582 methylation in study samples was assessed by real-time quantitative methylation-specific polymerase chain reaction analysis. We generated methylation index cutoff values for the detection of CIN3+ in physician-collected cervical samples for analysis of the self-collected group. Concordance between the physician-collected and self-collected groups was evaluated by Cohen's Kappa. Sensitivity, specificity and area under curve (AUC) were calculated for detection of CIN3+ lesions. Finally, we produced an optimal cutoff value with the best sensitivity from the self-collected groups. Results: We generated a methylation index cutoff value from physician-collected samples for detection of CIN3+. There were no significant differences in sensitivity, specificity of PAX1, SOX1 and ZNF582 between the self-collected and physician-collected groups. The methylation status of all three genes in the normal control samples, and the CIN 1, CIN2, CIN3, CIS, ACs/ ASCs and SCC samples showed reasonable to good concordance between the two groups (kappa = 0.443, 0.427, and 0.609 for PAX1, SOX1, and ZNF582, respectively). In determining the optimal cutoff values from the self-collected group, ZNF582 showed the highest sensitivity (0.77; 95% CI, 0.65-0.87) using a cutoff value of 0.0204. Conclusions: Methylation biomarker analysis of the three genes for detection of CIN3+ lesions shows reasonable to good concordance between the self-collected and physician-collected samples. Therefore, self-collection of samples could be adopted to decrease non-attendance and improve cervical screening.
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