Skip Navigation LinksHome > June 2014 - Volume 24 - Issue 5 > PAX1 Methylation as a Potential Biomarker for Cervical Cance...
International Journal of Gynecological Cancer:
doi: 10.1097/IGC.0000000000000155
Cervical Cancer

PAX1 Methylation as a Potential Biomarker for Cervical Cancer Screening

Kan, Yuen-Yee MD*; Liou, Yu-Ligh MS; Wang, Huei-Jen PhD; Chen, Chiao-Ying BS*; Sung, Li-Chi BS*; Chang, Chi-Feng PhD; Liao, Cheng-I MD

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Objectives: DNA methylation is a potential biomarker for early cancer detection. Previous studies suggested that the methylations of several genes are promising markers for the detection of cervical intraepithelial neoplasia at grade III or worse (CIN3+). The purpose of the present study was to explore the feasibility of these DNA methylation testing in cervical cancer screening.

Methods: A total of 443 women were recruited from the Yuan’s General Hospital. Cervical scrapings were collected for Papanicolaou (Pap) test by using cervical brushes, and the cytological data were used for analysis. The residual cells on the brush were preserved in phosphate-buffered saline solution at 4°C until DNA extraction. Then, the extracted DNA were used for molecular tests, which included human papillomavirus typing and quantification of the methylation levels for PAX1, SOX1, and NKX6-1 genes. Subjects who had abnormal Pap test results underwent colposcopy or biopsy with subsequent conization or major surgery when biopsy results revealed CIN2+. The final diagnosis for this group was confirmed by colposcopy or pathological examination. The study was approved by the institutional review board of Yuan’s General Hospital, and all the molecular tests were performed by ISO17025 certified laboratories.

Results: The sensitivity of PAX1m and SOX1m was greater than 80%, and the specificity of PAX1m and NXK6-1m was greater than 80% for the detection of CIN3+ lesions. PAX1m detection alone had a sensitivity and specificity of 86% and 85%, respectively, whereas when used as a cotest with the Pap test, the sensitivity and specificity were 89% and 83%, respectively.

Conclusions: PAX1m showed great potential as a biomarker for cervical cancer screening. When incorporating PAX1m detection into current screening protocol, the efficacy of screening could be greatly improved. Moreover, unnecessary referral for colposcopy and biopsy could be reduced up to 60%. However, prospective population-based studies are necessary for further implementation of this screening program.

© 2014 by the International Gynecologic Cancer Society and the European Society of Gynaecological Oncology.


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