Updated Pap smear detects ovarian, uterine cancers

Genetic analysis added to procedure offers way to reveal malignancies

A multipurpose version of a Pap smear can detect genetic signs of ovarian or uterine cancer in women, researchers report. When applied to the cervical swabs, the experimental analysis spotted genetic mutations in every sample from uterine cancer patients and in many from those with ovarian cancer.

The test is far from clinic-ready. But if confirmed in larger studies and developed into a usable “Papgene” test, as the study authors propose, the new approach could change cancer testing in women. The study appears in the Jan. 9 Science Translational Medicine.

Although the genetic screen caught uterine cancers more consistently, it is more apt to have a major impact on diagnosing ovarian cancer, says Shannon Westin, a gynecologic oncologist at the University of Texas M.D. Anderson Cancer Center in Houston who wasn’t part of the study team. While uterine cancers are often found due to vaginal bleeding and diagnosed with ultrasound tests, ovarian cancers remain hidden because they lack obvious symptoms and reliable screening tests. That makes the cancer deadly, she says.

Researchers identified 12 genetic mutations that show up in uterine or ovarian tumors. They reasoned that a Pap test could detect these mutations since some cancerous cells get shed from the ovaries and uterus and travel to the cervix, the conical structure where the uterus meets the vagina. A doctor swabs the cervix with a brush to get a sample of cells for a Pap smear, an exam that normally checks for aberrant cell growth related to cervical cancer and can also look for the genetic signature of the virus that causes it.

The researchers tested 46 Pap smears from cancer patients. The new test found at least one genetic mutation in all 24 samples taken from uterine cancer patients and in nine of 22 samples from ovarian cancer patients. Many of the cancers were still in an early stage at the time the Pap smears were performed, says study coauthor Luis Diaz Jr., an oncologist at Johns Hopkins University.

Tests on Pap smears from 14 women without cancer showed no signs of the 12 mutations.

“This study is really encouraging,” says Michael Melner, a molecular biologist and scientific program director for the American Cancer Society, based in Atlanta. “The strength of this is that Pap tests are already being done. You could just expand on that.”

Diaz says detection of ovarian cancer might have been hampered because cells that are shed from the ovaries must travel down the fallopian tubes and through the uterus to arrive at the cervix. Using sampling brushes that penetrate inside the cervix might better catch those cells, he says.

To establish its reliability, the new test will need to be repeated in hundreds more women with and without cancer, Diaz says, and he expects that more mutations will be added to the analysis as they prove specific to these cancers. “This is really a union of genomic medicine with just clinical anatomic know-how,” he says. The gene sequencing technology underling the test wasn’t available only a few years ago, he notes. If the test were available in a clinic today, it would add about $75 to the cost of a Pap smear, he estimates.

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