Combined clinical and genetic testing algorithm for cervical cancer diagnosis. Issue 1 (December 2016)

• Record Type: Journal Article
• Authors: Liou, Yu-Ligh; Zhang, Tao-Lan; Yan, Tian; Yeh, Ching-Tung; Kang, Ya-Nan; Cao, Lanqin; Wu, Nayiyuan; Chang, Chi-Feng; Wang, Huei-Jen; Yen, Carolyn; Chu, Tang-Yuan; Zhang, Yi; Zhang, Yu; Zhou, Honghao
• Is Part Of: Clinical epigenetics. Volume 8:Issue 1(2016)
• Page Start: 1
• Page End: 11
• Publication Date: 2016-12
• Subjects: Biomarkers -- Algorithm -- DNA methylation -- HPV16/18 -- Cervical cancer -- ZNF582 -- PAX1; Epigenesis -- Periodicals; Genetic regulation -- Periodicals; Human cytogenetics -- Periodicals; Human molecular genetics -- Periodicals; Cancer -- Genetic aspects -- Periodicals; 611.01816
• DOI: 10.1186/s13148-016-0232-3
• Languages: English
• ISSNs: 1868-7075

Abstract

Abstract Background Opportunistic screening in hospitals is widely used to effectively reduce the incidence rate of cervical cancer in China and other developing countries. This study aimed to identify clinical risk factor algorithms that combine gynecologic examination and molecular testing (paired box gene 1 (PAX1 ) or zinc finger protein 582 (ZNF582 ) methylation or HPV16/18) results to improve diagnostic accuracy. Methods The delta Cp of methylatedPAX1 andZNF582 was obtained via quantitative methylation-specific PCR in a training set (57 CIN2− and 43 cervical intraepithelial neoplasia ≥grade 3 (CIN3+) women), and the individual and combination gene sensitivities and specificities were determined. The detection accuracy of three algorithms combining gynecologic findings and genetic test results was then compared in a randomized case-control study comprising 449 women referred for colposcopic examination by gynecologists in the outpatient department of Xiangya Hospital between November 2011 and March 2013. Results Significant association was observed between CIN3+ and methylatedPAX1 orZNF582 in combination with HPV16/18 (OR:15.52, 95 % CI:7.73–31.18). The sensitivities and specificities of methylatedPAX1 orZNF582 combined with HPV16/18 for CIN3+ women were 89.2 and 76.0 %, or 85.4 and 80.1 %, respectively. Of the three algorithms applied to cohort data and validated in the study, two indicated 100 % sensitivity in detecting cervical cancer and a low rate of referrals for colposcopy. Conclusions These algorithms might contribute to precise and objective cervical cancer diagnostics in the outpatient departments of hospitals in countries with high mortality and low screening rates or areas with uneven resource distribution.