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Clinical Laboratories and Pathology Groups

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Clinical Laboratories and Pathology Groups

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Prenatal Testing Incidentally Finds Cancer in Mothers, Becomes Focus of New National Institutes of Health Long-term Study

Discovery could lead to new clinical laboratory testing for cancer screening in new mothers

Any clinical laboratory test that returns unexpected results is worth looking into more deeply. Such was the case with a recent study conducted by the National Institutes of Health (NIH), which investigated cases of pregnant women who received “unusual” results to prenatal lab tests conducted at a dozen labs in North America.

Following cancer screening protocols that included rapid whole-body magnetic resonance imaging, NIH scientists discovered “previously undetected cancers in 48.6% of pregnant people who had abnormal results for prenatal cell-free DNA (cfDNA) testing used to screen for chromosomal disorders in the fetus,” according to an NIH news release.

“They looked like healthy young women, and they reported themselves as being healthy,” Diana Bianchi, MD, head of the Prenatal Genomics and Therapy Section for the Medical Genetics Branch at the NIH’s National Human Genetics Research Institute, and senior author of the government study, told the Associated Press (AP).

While cfDNA tests are not diagnostic, pathologists and clinical laboratory managers involved in genetic testing are likely familiar with them. The blood tests are used by expectant mothers to assess risk of a fetus with an abnormal number of chromosomes that could suggest disorders such as Down Syndrome, according to ARUP Laboratories.

Unexpected results from tests draw attention. This one seems to have a chance to get more traction with labs because the results point to a prenatal test having some success predicting cancer, even if incidentally.

The researchers published their findings in the New England Journal of Medicine (NEJM) titled, “Prenatal cfDNA Sequencing and Incidental Detection of Maternal Cancer.”

“[The study participants] and their care providers need to take the results seriously and have additional testing because in that population there is a 48% risk of cancer,” Diana Bianchi, MD, senior author of the NIH study, told the AP. (Photo copyright: National Institutes of Health.)

Cancer Found in about Half of Those with Abnormal cfDNA

The NIH researchers started a long-term study, called IDENTIFY, to learn more about abnormal cfDNA results that could suggest cancer. Study participants must be:

  • Pregnant or postpartum with no known cancer.
  • Recipients of “unusual clinical cfDNA-sequencing results or results that are non-reportable (fetal aneuploidy status could not be assessed) from one of 12 different commercial laboratories,” they wrote in NEJM.

For the study’s initial cohort of 107 participants, researchers repeated cfDNA sequencing testing and coordinated standard medical diagnostic tests (such as Pap smears) and whole-body magnetic resonance imaging.

As reported by Ars Technica:

  • 52 women (48.6%) were found to have “hidden cancers.”
  • 32 had blood cancers.
  • 20 had solid tumors in the breast, bile duct, colon, pancreas, lung, kidney, bone, and adrenal gland.
  • 13 of the 20 with solid tumors were able to access “potentially curative treatments.”
  • 55 women did not have cancer and may have obtained an unreliable cfDNA result.

“In this study, 48.6% of participants who received unusual or nonreportable clinical cfDNA-sequencing results had an occult cancer (cancer of unknown primary).

“Further study of DNA-sequencing patterns that are suggestive of occult cancer during prenatal screening is warranted,” the researchers wrote in NEJM.

Follow-Up Testing Needed

Cancers found in the study participants “included colorectal, breast, lung and pancreatic cancers, as well as lymphoma, cholangiocarcinoma and renal carcinoma. The screening test analyzes placental DNA fragments circulating in the maternal bloodstream to identify an extra chromosome or to determine the baby’s sex,” according to the NIH news release.

Bianchi told AP the study results also pointed to a “very chaotic” pattern in DNA-sequencing of women with cancer, and that more research is needed to find out who should be screened for cancer.

Clinical laboratories and pathologists who analyze cfDNA tests could take a leadership role in assessing current standards for the tests, determining how suspicious results are reported, and suggesting needed changes. 

—Donna Marie Pocius

Is New Cervical Cancer Test Better Than a Pap Smear?

Intense research into cervical cancer detection and treatment has yielded significant progress in the past decade. One common cause of such cancer is the human papillomavirus (HPV). New developments involving HPV have produced thin-layer Pap smears, HPV testing, and HPV vaccines. Now, researchers in Italy are reporting a new twist in HPV screening and detection. In research published in the journal Lancet Oncology, Guglielmo Ronco, a cancer epidemiologist at the Centre for Cancer Prevention in Turin, reported that a new way to test for cervical cancer is more accurate than a pap smear alone and identified more dangerous lesions.

Clinicians can improve the specificity of DNA tests for HPV by testing for the presence of a protein that is over-expressed in cervical cancer cells, the new research shows. The molecular test tends to give more false positives, increasing the number of unneeded referrals for colposcopy, Ronco and colleagues reported online in the journal Lancet Oncology. (Carozzi F, et al “Use of p16-INK4A overexpression to increase the specificity of human papillomavirus testing: a nested substudy of the NTCC randomised controlled trial” Lancet Oncology 2008; DOI: 10.1016/S1470-2045(08)70208-0.)

DNA tests for HPV are more likely to pick up cases of high-grade cervical intraepithelial neoplasia (CIN) than conventional cytology, Ronco and colleagues reported. Since the molecular method gives more false positives, it tends to increase the number of unneeded referrals for colposcopy, Dr. Ronco and colleagues reported. To improve specificity, the researchers considered the cyclin-dependent kinase inhibitor p16-INK4A (p16), which is considered to be a marker of HPV infection, according to a report on the findings at www.medpagetoday.com.

Since only a small percentage of women who have an HPV infection actually develop cancer, the challenge for researchers is to identify those who have the highest risk for developing the disease. By testing for a the presence of P16, the researchers said they had identified a biomarker showing cell changes that indicated whether a woman was likely to have pre-cancerous lesions, Ronco and colleagues reported. “The marker shows there was some sort of disruption by the HPV virus,” Ronco said.

“Our data show that in HPV-positive women, p16-INK4A over-expression is strongly associated with the presence of histologically confirmed CIN2+, suggesting that it actually is a marker of progression,” Dr. Ronco said. “This study supports the application of triage by P16INK4A immunostaining in HPV-positive women,” he added.

Data from the U.S. National Cancer Institute show that an estimated 11,000 women in the United States would be diagnosed with this type of cancer and nearly 4,000 would die from it last year. Cervical cancer strikes nearly half a million women each year worldwide, claiming a quarter of a million lives. Studies show 26% of women aged 14 to 59 will contract HPV.

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