PAX1 methylation as a potential biomarker for cervical cancer screening.
OBJECTIVE
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 PAX1 and SOX1 was greater than 80%, and the specificity of PAX1 and NXK6-1 was greater than 80% for the detection of CIN3+ lesions. PAX1 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
PAX1 showed great potential as a biomarker for cervical cancer screening. When incorporating PAX1 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.
*Department of Obstetrics and Gynecology, Yuan's General Hospital, Kaohsiung; †iStat Biomedical Co, Ltd, Taipei; and ‡Department of Obstetrics and Gynecology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
Yuen-Yee
YY
Kan
Yu-Ligh
YL
Liou
Huei-Jen
HJ
Wang
Chiao-Ying
CY
Chen
Li-Chi
LC
Sung
Chi-Feng
CF
Chang
Cheng-I
CI
Liao
D000230:Adenocarcinoma / Q000175:diagnosis* / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000235:genetics; D003430:Cross-Sectional Studies; D019175:DNA Methylation; D055088:Early Detection of Cancer; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D008875:Middle Aged; D060787:Neoplasm Grading; D051761:Paired Box Transcription Factors / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011379:Prognosis; D055748:SOXB1 Transcription Factors / Q000235:genetics; D015996:Survival Rate; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000235:genetics; D014626:Vaginal Smears; D055815:Young Adult; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis* / Q000235:genetics
D014408:Biomarkers, Tumor; D018398:Homeodomain Proteins; C105201:NKX6-1 protein, human; D051761:Paired Box Transcription Factors; C490906:SOX1 protein, human; D055748:SOXB1 Transcription Factors; C070835:PAX1 transcription factor