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Pap test may reveal endometrial, ovarian cancer

Wednesday January 9, 2013
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Using cervical fluid obtained during routine Pap tests, researchers have developed a test to detect ovarian and endometrial cancer.

In a pilot study, the "PapGene" test, which relies on genomic sequencing of cancer-specific mutations, accurately detected all 24 endometrial cancers and nine of 22 ovarian cancers (41%), reported scientists at the Johns Hopkins Kimmel Cancer Center.

The investigators said larger-scale studies are needed before clinical implementation can begin, but they believe the test has the potential to pioneer genomic-based cancer screening tests.

The Papanicolaou test is widely and successfully used to screen for cervical cancers. However, no routine screening method is available for ovarian or endometrial cancers.

Since the Pap test occasionally contains cells shed from the ovaries or endometrium, cancer cells arising from these organs could be present in the fluid as well, said Luis Diaz, MD, associate professor of oncology at Johns Hopkins and director of the Swim Across America Laboratory (which is sponsored by a volunteer organization that raises funds for cancer research). "Our genomic sequencing approach may offer the potential to detect these cancer cells in a scalable and cost-effective way," Diaz said in a news release.

Cervical fluid of patients with gynecologic cancer carries normal cellular DNA mixed together with DNA from cancer cells, according to the investigators. Their task was to use genomic sequencing to distinguish cancerous from normal DNA.

The scientists had to determine the most common genetic changes in ovarian and endometrial cancers to prioritize which genomic regions to include in their test. They searched publicly-available genome-wide studies of ovarian cancer, including those done by other Johns Hopkins investigators, to find ovarian-cancer specific mutations. Such genome-wide studies were not available for the most common type of endometrial cancer, so they conducted genome-wide sequencing studies on 22 such cancers.

From the ovarian and endometrial cancer genome data, the researchers identified 12 of the most frequently mutated genes in both cancers and developed the PapGene test with this insight in mind.

The investigators then applied PapGene on Pap test samples from ovarian and endometrial cancer patients at The Johns Hopkins Hospital in Baltimore, Memorial Sloan-Kettering Cancer Center in New York City, the University of Sao Paulo in Brazil and ILSBio, a tissue bank. The new test detected both early- and late-stage disease in the endometrial and ovarian cancers tested. No healthy women in the control group were misclassified as having cancer.

The investigatorsí next steps include applying PapGene on more samples and working to increase the testís sensitivity in detecting ovarian cancer. "Performing the test at different times during the menstrual cycle, inserting the cervical brush deeper into the cervical canal and assessing more regions of the genome may boost the sensitivity," said Chetan Bettegowda, MD, PhD, assistant professor of neurosurgery at Johns Hopkins.

Together, ovarian and endometrial cancers are diagnosed in nearly 70,000 women in the United States each year, and about a third will die from their disease.

"Genomic-based tests could help detect ovarian and endometrial cancers early enough to cure more of them," said graduate student Yuxuan Wang, who noted the cost of the test could be similar to current cervical fluid HPV testing, which is less than $100.

The study appears in the Jan. 9 issue of Science Translational Medicine. The study abstract is available at http://stm.sciencemag.org/content/5/167/167ra4.


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