*Department of Research, Center for Cervical Cancer Prevention, Buddhist Tzu Chi General Hospital, and daggerSchool of Medicine, Graduate Institute of Medical Science, Tzu Chi University, Hualien; double daggerDepartment of Obstetrics and Gynecology, Tri-Service General Hospital; section signLaboratory of Epigenetics, National Defense Medical Center, Taipei; and parallelDepartment of Occupational Medicine, Buddhist Tzu Chi General Hospital, paragraph signGraduate Institute of Clinical Medicine, and #Department of Obstetrics and Gynecology, Buddhist Tzu Chi General Hospital, Tzu Chi University, Hualien, Taiwan, Republic of China.
Int J Gynecol Cancer. 2010 May; 20(4):513-519.
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.
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.
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.
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.
PMID: 20442585 [PubMed - as supplied by publisher] Source: National Library of Medicine.
