A new study that proposes a three-in-one test for gynecologic cancers -- combining a traditional Pap smear for cervical cancer with a DNA test for gene mutations linked to endometrial and ovarian cancer -- underscores the promise of molecular screening for early detection of endometrial and ovarian cancers, but also suggests that such tests are not yet ready for clinical use, write the authors of a commentary in this week's issue of Science Translational Medicine.
"Pap smears have had a tremendous impact in reducing the rate of cervical cancer in the United States," says Andrea Myers, MD, PhD, of Dana-Farber Cancer Institute, a co-author of the commentary on the study. "The lack of an equally effective screening test for women at high risk for endometrial or ovarian cancer has created a great deal of interest in developing tests that could identify these cancers by their genetic 'signature' -- the collection of specific mutations within them. This new study is an important step in that direction."
The study, led by Isaac Kinde and Luis Alberto Diaz, MD, of Johns Hopkins Kimmel Cancer Center, used advanced DNA sequencing technology to look for mutations in 12 genes associated with endometrial or ovarian cancer in cells collected for Pap tests. In Pap samples from women known to have endometrial or ovarian cancer, the screening test -- dubbed "Papgene" -- often found one or more of the mutations. The samples from women without cancer, by contrast, showed no mutations.
Myers notes that the test proved to be highly sensitive for endometrial cancer: every sample from women known to have the disease tested positive for mutations. However, it captured only 40 percent of patients known to have ovarian cancer -- a disease for which there is a particularly urgent need for an early-detection test.
While Papgene didn't find mutations in women without cancer, the test was performed on only 19 samples. Much larger numbers will be needed to ensure the test doesn't mistakenly indicate cancer where none exists, Myers remarked.
"The DNA sequencing technologies that have changed our understanding of the molecular nature of cancer are beginning to be explored for clinical usefulness, and this study is a good example," says Myers. "It's clear that putting a screening technique to the test requires just as much rigor as the basic science discovery process itself."
The commentary's other co-authors are Shannon Westin, MD, MPH, and Gordon Mills, MD, PhD, of the University of Texas MD Anderson Cancer Center.
- I. Kinde, C. Bettegowda, Y. Wang, J. Wu, N. Agrawal, I.-M. Shih, R. Kurman, F. Dao, D. A. Levine, R. Giuntoli, R. Roden, J. R. Eshleman, J. P. Carvalho, S. K. N. Marie, N. Papadopoulos, K. W. Kinzler, B. Vogelstein, L. A. Diaz. Evaluation of DNA from the Papanicolaou Test to Detect Ovarian and Endometrial Cancers. Science Translational Medicine, 2013; 5 (167): 167ra4 DOI: 10.1126/scitranslmed.3004952
- S. N. Westin, G. B. Mills, A. P. Myers. Repurposing the Pap Smear: One Step Closer to Gynecologic Cancer Screening. Science Translational Medicine, 2013; 5 (167): 167ps1 DOI: 10.1126/scitranslmed.3005411
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