Screening Tool for Gynecologic Cancers Assessed

Researchers at Johns Hopkins University in Baltimore, MD, have developed a test called PapSEEK that detects gynecologic cancers by analyzing DNA samples collected during routine Pap tests for mutations and aberrations in chromosome number. In a recent study, the test proved to be a promising tool for improving the sensitivity and specificity of detection for endometrial and ovarian cancers.

“It's a substantial problem that we aren't always able to detect these cancers at either a precancerous or early cancerous stage, when the disease is most curable,” explains Amanda Fader, MD, of the Department of Gynecology and Obstetrics at Johns Hopkins. Because 90,000 women are diagnosed with and 25,000 women die of these diseases every year, “the goal with the development of PapSEEK is to move the needle with cancer mortality in the gynecologic cancers, and to help more women preserve fertility.”

PapSEEK tests DNA in fluids obtained during a Pap test for 18 genetic mutations indicative of endometrial and ovarian cancers, as well as aneuploidy, which is also linked to the cancers. In a recent study, Fader, study leader Nickolas Papadopoulos, PhD, and colleagues investigated the ability of PapSEEK to detect the malignancies using DNA samples from 1,658 women, including 656 already diagnosed with endometrial or ovarian cancer, and 1,002 healthy controls (Sci Transl Med 2018;10:eaap8793).

The test detected 81% of endometrial and 33% of ovarian cancers, with a false-positive rate of 1.4%, when performed on cervical samples taken during a Pap test. When the test was performed on intrauterine samples collected with a tool called a Tao brush, it detected 93% of endometrial and 45% of ovarian cancers, with no false positives. Sensitivity for ovarian cancer increased to 63% when researchers analyzed Pap samples and checked plasma for circulating tumor DNA (ctDNA).

Fader is optimistic about the group's recent findings, but PapSEEK “is not yet ready for prime time,” she acknowledges. “We are likely a couple of studies away from identifying whether the current platform will be commercialized, but it is our hope.”

The researchers are conducting a larger study to evaluate the effectiveness of different diagnostic approaches, including Pap versus Tao sampling, and testing plasma for ctDNA alone. Fader says the group is particularly interested in improving detection of ovarian cancer, especially in the early stages, and refining the genetic platform to detect even smaller amounts of DNA.

“It's a challenge for researchers to develop a test that is not only effective at detecting ovarian and endometrial cancers, but one that is not too invasive and is acceptable to women,” Fader explains. “If PapSEEK is validated, then it could easily be incorporated by primary care providers, internal medicine specialists, and gynecologists in routine gynecological screenings for women.”

Charles Drescher, MD, a gynecologic oncologist at Fred Hutchinson Cancer Research Center in Seattle, WA, who was not involved in the study, praises it for advancing research on mutational testing for endometrial and cervical cancers.

“This is a powerful study with large numbers that nicely lays out a solid foundation for how to move forward, and provides information about where we should be looking in terms of designing the next generation of studies to evaluate for clinical utility,” he says. Next, he would like to see a large-scale, prospective study on PapSEEK that includes samples from patients with benign lesions that mimic cancer.

“If the performance characteristics are sufficient, I think it will be something that should be relatively easy to implement as part of care, and that is very appealing,” he says. – Catherine Caruso

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