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Quantitative Analysis of Methylation Status of the PAX1 Gene for Detection of Cervical Cancer
  1. Tien-Hung Huang, MS*,,
  2. Hung-Chen Lai, MD, PhD,§,
  3. Hwan-Wun Liu, MD, PhD,,
  4. Cuei Jyuan Lin, MS*,,
  5. Kai-Hung Wang, MS*,,
  6. Dah-Ching Ding, MD, PhD,# and
  7. Tang-Yuan Chu, MD, PhD*,,#
  1. *Department of Research, Center for Cervical Cancer Prevention, Buddhist Tzu Chi General Hospital, and
  2. School of Medicine, Graduate Institute of Medical Science, Tzu Chi University, Hualien;
  3. Department of Obstetrics and Gynecology, Tri-Service General Hospital;
  4. §Laboratory of Epigenetics, National Defense Medical Center, Taipei; and
  5. Department of Occupational Medicine, Buddhist Tzu Chi General Hospital,
  6. Graduate Institute of Clinical Medicine, and
  7. #Department of Obstetrics and Gynecology, Buddhist Tzu Chi General Hospital, Tzu Chi University, Hualien, Taiwan, Republic of China.
  1. Address correspondence and reprint requests to Tang-Yuan Chu, MD, PhD, Department of Obstetrics and Gynecology, Buddhist Tzu Chi General Hospital, 707, Section 3, Chung-Yang Rd, Hualien 970, Taiwan, Republic of China. E-mail: tychu{at}


Objective: Although aided by high-risk human papillomavirus (HPV) DNA test, early detection of cervical cancer is still a challenge. Hypermethylation of the paired boxed gene 1 (PAX1) was recently reported as a characteristic of cervical cancer. This study designed a quantitative measure of PAX1 methylation and compared its efficacy to the currently available Hybrid Capture 2 (HC2) HPV test in detection of cervical cancer.

Methods: Using real-time quantitative methylation-specific polymerase chain reaction, we measured the percentage of PAX1 methylation in cervical scrapings obtained from a hospital-based cohort of women with cervical neoplasia of different severities and compared the efficacy of diagnosis of cervical cancer to that of the HC2 HPV test.

Results: From 73 cervical scrapings, with diagnoses of normal (n = 17), cervical intraepithelial neoplasm 1 (CIN1; n = 10), CIN2 (n = 18), CIN3 (n = 14), and invasive cancer (n = 14), the percentage of PAX1 methylation was determined. The percent of methylated reference of invasive cancer (mean [SE], 56.7 [7.1]) was significantly higher than CIN3 (6.5 [2.3]) and the other milder lesions (1.0 [0.3]; P < 0.0001). At a cutoff percent of methylated reference value of 4.5, PAX1 methylation was found in 100% of invasive cancer tissue as compared with 0% of normal tissue, 10% of CIN1, 11% of CIN2, and 43% of CIN3 (P < 0.0001). As a comparison, the HC2 HPV test result was positive in 5.9% of normal tissue, 70% of CIN1, 55.6% of CIN2, 71.4% of CIN3, and 100% of invasive cancer. In addition to cancer tissue, methylation of PAX1 was also found in normal tissue adjacent to the cancer lesion (9/11, 82%) but much less in the remote normal tissues (2/5, 40%), indicating a field methylation.

Conclusions: In this hospital-based study, quantitative measurement of PAX1 hypermethylation in cervical scrapings is highly sensitive and is more specific than HC2 in detection of cervical cancer.

  • PAX1
  • DNA methylation
  • Cervical cancer
  • HPV test
  • Field methylation

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