A test that uses cervical fluid obtained during routine Pap tests to detect ovarian and endometrial cancers has been developed. A pilot study of the PapGene test, which relies on genomic sequencing of cancer-specific mutations, accurately detected all 24 (100%) endometrial cancers and nine of 22 (41%) ovarian cancers.

The Papanicolaou (Pap) test examines cells collected from the cervix for microscopic signs of cancer and has been widely and successfully used to screen for cervical cancers. However, both ovarian and endometrial cancers lack routine screening methods. Together, ovarian and endometrial cancers are diagnosed in nearly 70,000 women in the United States each year, and about one-third of those women will die from their disease.

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, explained Luis Diaz, MD, associate professor of oncology at Johns Hopkins Kimmel Cancer Center. Diaz added, “Our genomic sequencing approach may offer the potential to detect these cancer cells in a scalable and cost effective way.”

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The researchers found that cervical fluid of patients with gynecologic cancer carries abnormal cellular DNA mixed together with DNA from cancer cells. They used genomic sequencing to distinguish cancerous from normal DNA.

The scientists had to determine the most common genetic changes in ovarian and endometrial cancers in order to prioritize which genomic regions to include in their test. They searched publically 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 of these endometrial cancers. From the ovarian and endometrial cancer genome data, the Johns Hopkins-led team 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. 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 investigators’ next steps include applying PapGene on more samples and working to increase the test’s 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,” says Chetan Bettegowda, MD, PhD, assistant professor of neurosurgery at Johns Hopkins.

These results were published in Science Translational Medicine (2013; doi:10.1126/scitranslmed.3004952).