Johns Hopkins: Cervical fluid samples gathered during routine Papanicolaou
(Pap) tests are the basis of a new screening test for endometrial and
ovarian cancers developed by researchers at the Johns Hopkins Kimmel Cancer Center. PapSEEK detects mutations in DNA that have been identified for
specific cancers sooner. Earlier detection of cancer could lead to
earlier treatment and potentially better outcomes for patients. The test uses cervical fluid samples to look for mutations in
18 genes, which are highly or commonly mutated in endometrial or ovarian
cancers, and aneuploidy, the presence of abnormal numbers of
chromosomes in cells. The researchers said their results showed the
potential for mutation-based diagnostics to detect endometrial and
ovarian cancers earlier.
Their findings were published in the March 21 issue of Science Translational Medicine.
“More than 86,000 U.S. cases of endometrial and ovarian cancer
were diagnosed in 2017. Treatment often involves surgery and, in some
cases, chemotherapy or radiation,” said Amanda Nickles Fader, M.D.,
director of the Johns Hopkins Kelly Gynecological Oncology Service,
Department of Gynecology and Obstetrics, and a corresponding author on
this study.
“Additionally for young women who are diagnosed, loss of
fertility is common. If we could detect the cancer earlier using a test
like PapSEEK, the potential to achieve more cures and preserve fertility
in select women could be realized.”
Most cancers are curable if they are detected early, and the
researchers are exploring ways to use cancer gene discoveries to develop
cancer screening tests to improve cancer survival. They announced the
development of CancerSEEK, a single blood test that screens for eight
cancer types, and UroSEEK, a test that uses urine to detect for bladder
and upper tract urothelial cancer.
PapSEEK targets the most common and most lethal gynecological
cancers, endometrial and ovarian cancer. There is currently no screening
test for endometrial cancer and, due to the obesity epidemic, it is on
the rise, particularly in younger women.
“Gynecological cancers are responsible for approximately 25,000
deaths per year and are the third leading cause of cancer-related
mortality,” said Nickolas Papadopoulos, Ph.D.,
a senior author and an investigator at the Ludwig Center at Johns
Hopkins. “Most of the deaths are caused by tumors that metastasize prior
to the onset of symptoms. With PapSEEK, we are aiming to detect these
cancers early when they are most curable.”
Since fluid from the Pap test occasionally contains cells from
the endometrium or ovaries, researchers found they could detect cancer
cells from these organs that are present in the fluid.
The researchers studied 1,958 samples obtained from 1,658
women, including 658 endometrial or ovarian cancer patients and 1,002
healthy controls. Some participants provided two samples. Pap brush
samples were obtained from 382 endometrial cancer patients and 245
ovarian cancer patients. PapSEEK was nearly 99 percent specific for
cancer, and it detected 81 percent of endometrial cancers (78 percent
were early-stage cancers) and 33 percent of ovarian cancers (34 percent
were early-stage cancers).
Obtaining cervical fluid samples using a Tao brush, which
extends further into the cervical canal and collects cells closer to
where the cancers could originate, improved the sensitivity of the test.
Testing plasma samples with Pap brush samples also increased the test’s
sensitivity.
Lucy Gilbert, M.D. MSc FRCOG, director of gynecologic oncology at McGill
University Health Centre, said, “This allows sampling closer to where
the cancers originated. Intrauterine sampling proved particularly
important for increasing the detection of ovarian cancer.”
Of the 123 endometrial cancer patients studied using Tao brush
samples, PapSEEK identified cancer 93 percent of the time. Of the 51
ovarian cancer patients studied, 45 percent tested positive for cancer
with PapSEEK. There were no false-positive results.
The Tao brush is not commonly used in the United States but is
approved by the U.S. Food and Drug Administration for endometrial
sampling. When the plasma and Pap brush samples were both tested, the
sensitivity of the test for ovarian cancer increased to 63 percent.
More than 63,000 women are diagnosed with endometrial cancer in
the U.S. each year, and more than 11,000 die each year from the
disease. Ovarian cancer is less common but more lethal, affecting more
than 22,000 women and killing about 14,000 in the U.S. each year.
“Diagnostic tests do not always reliably distinguish benign
conditions from cancer, leading to unnecessary procedures,” said Nickles
Fader. “The high mortality associated with some gynecologic cancers
makes screening a priority, and new diagnostic approaches are urgently
needed.”
“Our study demonstrates the ability to detect endometrial and
ovarian cancer using cervical fluids obtained using two different
methods,” said Yuxuan Wang, first author on the study.