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  1. Yuen-Yee Kan, MD*,
  2. Yu-Ligh Liou, MS,
  3. Huei-Jen Wang, PhD,
  4. Chiao-Ying Chen, BS*,
  5. Li-Chi Sung, BS*,
  6. Chi-Feng Chang, PhD and
  7. Cheng-I Liao, MD
  1. *Department of Obstetrics and Gynecology, Yuan’s General Hospital, Kaohsiung;
  2. iStat Biomedical Co, Ltd, Taipei; and
  3. Department of Obstetrics and Gynecology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
  1. Address correspondence and reprint requests to Yuen-Yee Kan, MD, Department of Obstetrics and Gynecology, Yuan’s General Hospital, Kaohsiung, Taiwan, No.162 Cheng Kung 1st Rd, Kaohsiung 80249, Taiwan. E-mail: kyy_gyn@yahoo.com.tw; Cheng-I Liao, MD, Department of Obstetrics and Gynecology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, 386 Ta-Chung 1st Rd, Kaohsiung, Taiwan 81346. E-mail: justice.obgy{at}gmail.com.

Abstract

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.

  • Papanicolaou test (Pap)
  • Human papillomavirus (HPV)
  • Paired box gene 1 (PAX1)
  • Sex determining region Y-box 1 (SOX1)
  • NK6 transcription factor-related locus 1 (NKX6-1)

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Footnotes

  • This research was funded by iStat Biomedical Co, Ltd, Taipei, Taiwan.

  • The authors declare no conflicts of interest.