Can a Pap test one day be used to diagnose ovarian, endometrial cancers?
A foundational study in Science Translational Medicine suggests that cervical fluids gathered during routine Pap tests may have potential in screening for endometrial and ovarian cancers. The findings are from a comparative analysis of samples form women with endometrial or ovarian cancer and controls that were tested with PapSEEK, a test that looks for genetic alterations common in endometrial and ovarian cancers.
For the research, the authors used 1915 samples from 1658 women, 656 of whom had endometrial or ovarian cancer and 1002 of whom were healthy. The researchers noted that tumor DNA can be detected in the vaginal tract of women with ovarian cancer, while endometrial and ovarian cancers shed cells that collect at the cervix. As a result, tumor DNA can be found in the fluids obtained during a routine Pap test.
Because the amount of DNA shed from neoplastic cells was expected to be a small fraction of the total DNA collected from the Pap brush samples, the researchers used a sensitive, PCR-based error-reduction technology to identify mutations. Primers were designed to amplify 139 regions, covering 9392 distinct nucleotide positions within the 18 genes of interest.
The researchers applied this assay to Pap brush samples of 382 women with endometrial cancer, 245 women with ovarian cancer, and 714 women without cancer. Detectable mutations were found in 81% of patients with endometrial cancer (95% CI, 76 to 84%), including 78% of patients with early-stage disease (stages I and II) and 89% of patients with late-stage disease (stages III and IV). In the ovarian cancer patients, 29% had detectable mutations in their Pap brush samples (95% CI, 24 to 36%). This included 28% of patients with early-stage disease and 30% of patients with late-stage disease. Of the women without cancer, 1.3% had a detectable mutation, yielding a specificity of ~99%.
Sensitivity of the assay test was improved by use of a Tao brush, which extends further into the cervical canal. With the tool, PapSEEK identified cancer 93% of the time in the 123 patients studied. Of the 51 ovarian cancer patients studied, 45% tested positive for cancer.
While the authors noted that their findings are promising, they identified a few limitations. The research was retrospective rather than prospective and many of the patients involved in the study had already been diagnosed with cancer, which meant that in many cases, the disease was not in as early a stage as would be expected in a screening setting. Another limitation is that in some patients with ovarian cancer, mutations detectable in Pap or Tao brush samples were not identical to the ones in the primary tumors. While this study is foundational at this point, the authors noted the possible importance of it, given that there is currently no screening test for endometrial cancer.