FRESH SCIENCE for Clinicians

News about basic science of interest and relevance for cancer clinicians

Friday, January 11, 2013

The Pap as a Diagnostic for Endometrial and Ovarian Cancer?

The development and widespread use of the Pap smear dramatically reduced the incidence and mortality of cervical cancer. And the relatively recent addition of HPV DNA testing to liquid Pap tests has further increased their utility.


Now, investigators at Johns Hopkins Medical Institutes and colleagues propose that the test can be adapted to diagnose endometrial cancer and some ovarian cancers.


The new work, published in the January 9 issue of Science Translational Medicine, is proof of principle that DNA assays can detect some of these tumors in liquid Pap samples. A multiplex sequencing test designed to detect 12 mutations common to these cancers accurately identified 100% of endometrial cancers (24 out of 24) and 41% of ovarian cancers (9 out of 22).


The authors, led by Isacc Kinde and colleagues, caution that there is a ways to go before the tests could be routinely used in the clinic.


Shannon Westin, from MD Anderson Cancer Center, and colleagues emphasize the same point in an accompanying editorial. They also point out that while piggybacking endometrial and ovarian cancer screening tests on the widely used Pap test is clever, it might not be as straightforward as one would hope. For example, the use of the Pap test for cervical cancer screening is being scaled back, with longer intervals recommended between tests and consideration of stopping it altogether for older women -- women who are at the highest risk of both endometrial and ovarian cancer.


Additionally, Dr. Westin and colleagues note that developing a CLIA-approved test might be technically challenging because the assay is based on multiplex sequencing. Also, even with next -generation sequencing costs dropping like a rock, the technology might exceed what a widespread test could bear.


All the cautions aside, the study does prove that ovarian and endometrial cancer cells are present for detection in the samples and that the assay can detect mutant DNA that represents less than 0.01% of the DNA copies in the sample. The test also had 100% specificity, albeit in a small sample of just 14 healthy control subjects.


Thus there are reasons for (cautious) enthusiasm: A screening test for gynecologic cancers may be possible.


One interesting aside, from my point of view, is that the paper includes whole genome sequencing data from 22 endometrial tumors and matched controls. To develop their multiplex test, the team needed to know what mutations are common in the various subtypes of ovarian and endometrial cancers. They could find data in the literature on ovarian tumor mutations (e.g., from The Cancer Genome Atlas) but little for endometrial cancer and therefore obtained their own.


Not too long ago, whole genome sequencing of that many tumors and controls would have been a paper all on its own. The fact that the researchers rolled those data into the screening study, and noted them almost in passing, shows just how far the field of cancer genomics has come in a very short time.