Ovarian, Endometrial Cancers Detected Using Cervical Fluid

Scientists have developed a test to detect ovarian and endometrial cancers, which relies on genomic sequencing of cancer-specific mutations.

Occasionally the Pap test contains cells shed from the ovaries or endometrium and cancer cells arising from these organs could be present in the cervical fluid as well. Luis Diaz, MD, associate professor of oncology at Johns Hopkins said, "Our genomic sequencing approach may offer the potential to detect these cancer cells in a scalable and cost effective way."

During routine Pap tests, at the Johns Hopkins Kimmel Cancer Center (Baltimore, MD, USA), scientists accurately detected all 24 (100%) endometrial cancers and 9 of 22 (41%) ovarian cancers. The study is published in the January 9, 2013, issue of the journal Science Translational Medicine. Larger scale studies are needed before clinical implementation can begin, but the investigators believe the test has the potential to pioneer genomic-based cancer screening tests.

The scientists determined the most common genetic changes in ovarian and endometrial cancers in order to choose which genomic regions to include in their test. They searched publicly available genome-wide studies of ovarian cancer 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 applied PapGene on Pap test samples from ovarian and endometrial cancer patients at The Johns Hopkins Hospital, Memorial Sloan-Kettering Cancer Center, 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 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," said Chetan Bettegowda, MD, PhD, assistant professor of neurosurgery at Johns Hopkins.

PapGene is a high-sensitivity approach for the detection of cancer-specific DNA mutations, according to the investigators; however, false mutations can be erroneously created during the many steps––including amplification, sequencing, and analysis––required to prepare the DNA collected from a Pap test specimen for sequencing. The investigators needed to build a safeguard into PapGene's sequencing method, designed to weed out artifacts that could lead to misleading test results.

Related Links:
Johns Hopkins Kimmel Cancer Center