Promoter Hypermethylation of Tumor Suppressor Genes in Urine from Patients with Cervical Neoplasia
- Qinghua Feng1,
- Stephen E. Hawes2,
- Joshua E. Stern1,
- Amadou Dem3,
- Papa Salif Sow3,
- Birama Dembele3,
- Papa Toure3,
- Pavel Sova1,
- Peter W. Laird4 and
- Nancy B. Kiviat1
- 1Department of Pathology, School of Medicine, and 2Department of Epidemiology, School of Public Health and Community Medicine, University of Washington, Seattle, Washington; 3Department of Infectious Diseases, University of Dakar, Senegal; and 4Keck School of Medicine, University of Southern California, Los Angeles, California
- Requests for reprints:
Qinghua Feng, Department of Pathology, University of Washington, 815 Mercer Street, Seattle, WA 98109. Phone: 206-897-1583; Fax: 206-897-1334. E-mail: qf{at}u.washington.edu
Abstract
We examined the feasibility of using detection of high-risk human papillomavirus (HPV) DNA in combination with the presence of aberrantly methylated genes (DAPK1, RARB, TWIST1, and CDH13) for urine-based cervical cancer screening. Urine samples from 129 Senegalese women, aged 35 years or older, 110 with (same day) biopsy-proven cervical neoplasia [cervical intraepithelial neoplasia grade 1 (CIN-1): n = 9; CIN-2–3/carcinoma in situ (CIS): n = 29; invasive cervical cancer (ICC): n = 72], and 19 without cervical neoplasia on biopsy were examined. Hypermethylation of at least one of the four genes identified 62% of ICC and 28% of CIN-2–3/CIS and was present in only 4% of CIN-1 or normal urines. High-risk HPV DNA was detected in urine in 70% of those with biopsy-proven ICC, 59% of those with CIN-2–3/CIS on biopsy, 44% of those with CIN-1 on biopsy, and only 11% of women negative for cervical neoplasia on biopsy. Urine-based detection of either high-risk HPV or hypermethylation of any of the four genes identified 84% of ICC, 64% of CIN-2–3/CIS, 44% of CIN-1, but only 19% of women negative for cervical neoplasia. The sensitivity for detection of CIN-2–3/CIS/ICC by high-risk HPV DNA or aberrant DNA methylation of four genes seems to be comparable to that of an exfoliated cervical cytology. This study shows the potential feasibility of using molecular markers detected in urine for cervical cancer screening. (Cancer Epidemiol Biomarkers Prev 2007;16(6):1178–84)
Footnotes
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Grant support: NIH/National Cancer Institute (CA85050).
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The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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Note: Informed consent was obtained according to procedures approved by the Human Subjects Committee of the University of Washington and the Senegalese National AIDS Committee.
The authors have no commercial or other associations that might pose a conflict of interest.
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- Accepted March 30, 2007.
- Received August 15, 2006.
- Revision received February 3, 2007.
