Pap Test to Detect Ovarian, Endometrial Cancers?

By Kathleen Doheny
WebMD Health News

Reviewed by Laura J. Martin, MD

Jan. 9, 2013 -- A new test for ovarian and endometrial cancers looks at cervical fluid obtained during a routine Pap test to detect genetic mutations linked with the cancers.

Although the research is in early stages, the test did well in detecting these cancers, says researcher Yuxuan Wang, a graduate student at the Ludwig Center for Cancer Genetics and Therapeutics at the Johns Hopkins University's Kimmel Cancer Center in Baltimore.

If ongoing research bears out, the new test could someday become a routine screening test, much like the Pap test is for cervical cancer, she says.

"This would not add anything to the current [Pap] procedure," Wang says. "All we do is take part of the sample for DNA testing.''

The cervical fluid collected during a Pap smear contains normal DNA and, if a person has cancer, DNA from those cancer cells.

The researchers used genomic sequencing to pick out the cancerous DNA from the normal DNA.

The study is published in Science Translational Medicine.

Problems in Detecting Ovarian, Endometrial Cancers

Widespread use of the Pap test has reduced deaths from cervical cancer and increased early detection. But finding reliable screening tests for ovarian and endometrial cancers has been elusive.

More than 69,000 U.S. women were expected to get a diagnosis of either ovarian or endometrial cancer in 2012.

If endometrial cancer is suspected, a doctor may order a transvaginal ultrasound. If ovarian cancer is suspected, a doctor may order a blood test that looks for CA-125, a protein found at high levels in some ovarian cancer patients.

Neither test is as reliable as a screening test, the researchers say. The U.S. Preventive Services Task Force and the American Cancer Society do not recommend general routine screening for endometrial or ovarian cancer.

Examining Pap Test Fluid

During a Pap test, cells collected from the cervix are examined for signs of cancer. The DNA in the Pap sample may also be examined for human papillomavirus (HPV), which causes cervical cancer.

The cervical fluid collected during the Pap test can also contain cells shed from the ovaries or the uterine lining (the endometrium).

Cancer cells from either the ovaries or endometrium could also be present in the fluid, the researchers say.

In the new study, the researchers determined the most common genetic mutations found in ovarian and endometrial cancers.

"We ended up with 12 genes," Wang says. The test they developed, called the PapGene test, looks for mutations on those 12 genes.

They searched for the mutations in 24 endometrial cancer tissue samples and 22 ovarian cancer tissue samples.

Mutations were found in all 46 samples.

They looked at the Pap test to see if the same mutations were found as they found in the tissue samples.

For the endometrial samples and Pap tests, 100% matched, Wang says.

For the ovarian samples and Pap tests, they found 41% matched.

The researchers then looked at 14 Pap tests from women known to be cancer-free. "We found no cancer-specific mutations in the fluid," Wang says.

The cost of the test, Wang says, could be less than $100.

The research was funded by Swim Across America (a fund-raising organization for cancer research), the National Cancer Institute, the National Institutes of Health, and numerous other sources.

Several researchers on the study are co-founders of Inostics and Personal Genome Diagnostics, companies involved in DNA blood tests and genetic sequencing.

Several researchers serve on the companies' scientific advisory boards and own stock. The companies have licensed patent applications related to the tests from Johns Hopkins.

Perspective on Test for Ovarian, Endometrial Cancers

"Obviously it's at the early stages," says Michael H. Melner, PhD, scientific program director of molecular genetics and biochemistry in cancer for the American Cancer Society. He reviewed the findings for WebMD.

However, he says, the test ''shows a lot of potential."

In theory, Melner says, looking at genetic mutations known to be linked with certain cancers would be more accurate than looking at some other biological indicators.

Looking at such biomarkers to detect cancer is not foolproof. "We now know that certain of these biomarkers get released during inflammatory diseases that are not cancer," he says.

For instance, CA-125 can be found in high levels in cancer-free women with pelvic inflammatory disease.

Many researchers are working to develop genetic maps of certain cancers, Melner says. As they build these maps and reach agreement, he says, the hope is to detect the cancer in the very early stages.

Another plus of the PapGene test, he says, is that ''you are using samples that are already collected for another technique."

But he cautions that much more study is needed. "It is going to take some time," he says.

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SOURCES: Kinde, I. Science Translational Medicine, Jan. 9. 2013. Yuxuan Wang, graduate student, Ludwig Center for Cancer Genetics and Therapeutics, Johns Hopkins Kimmel Cancer Center, Baltimore. Michael H. Melner, PhD, scientific program director, molecular genetics and biochemistry in cancer, American Cancer Society, Atlanta.

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