Pap Test Fluids May Contain DNA Useful for Endometrial, Ovarian Cancer Diagnosis

Cervical fluid samples gathered during routine Papanicolaou (Pap) tests can potentially be used for screening test women for endometrial and ovarian cancers, according to a study published March 21 in Science Translational Medicine. While the PapSEEK test needs validation in a large, prospective study, the authors are hopeful that the test's ability to detect DNA mutations associated with gynecological cancers can lead to earlier detection and, hopefully, improved outcomes.

Previous studies have shown that endometrial and ovarian cancers shed cells that collect at the cervix, thus making DNA samples feasible to be collect during routine Pap testing.

In the present study, researchers from Johns Hopkins University analyzed 1,958 samples collected from 1,658 women, including 658 endometrial or ovarian cancer patients and 1,002 healthy controls. Pap brush samples were obtained from 382 endometrial cancer patients and 245 ovarian cancer patients. Additionally, samples using a Tao brush, which extends further into the cervical canal and collects cells closer to where the cancers could originate, were collected in 123 endometrial cancer patients and 51 ovarian cancer patients studied. Analysis of samples examined mutations in 18 genes, which are highly or commonly mutated in endometrial or ovarian cancers, and aneuploidy using a polymerase chain reaction–based, multiplex test.

The researchers found that in Pap brush samples from endometrial cancer patients, 81 percent were positive, including 78 percent of patients with early-stage disease. The sensitivity of Pap brush samples in ovarian cancer patients was lower—33 percent, including 34 percent of patients with early-stage disease. For healthy controls, the PapSEEK test was positive in 1.4 percent of women (specificity, approximately 99 percent).

Intrauterine sampling with a Tao brush increased the detection of malignancy compared to the endocervical sampling with a Pap brush to 93 percent of patients with endometrial cancer and 45 percent of patients with ovarian cancer. There were no false positives (specificity, 100 percent).

The authors say the cost of a PapSEEK test would be more than the cost of a Pap test, but comparable to other screening modalities including colonoscopy and mammography.

Takeaway: Researchers are hopeful that fluids obtained during routine Pap testing may contain DNA shed from endometrial and ovarian cancers, thus enabling earlier detection of these gynecological cancers.