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11:01 am
Fri January 11, 2013

Pap Test May Detect More Than Just Cervical Cancer

Originally published on Fri January 11, 2013 12:03 pm



This is SCIENCE FRIDAY, I'm Ira Flatow. Pap tests are routinely used to screen women for signs of cervical cancer, but now researchers from Johns Hopkins University in Baltimore say the tests might be able to detect ovarian and uterine cancers as well.

In a study published this week in Science Translational Medicine, doctors analyzed genetic material from Pap smears to look for known mutations that signal the presence of ovarian or uterine cancer. It's part of a growing trend in cancer research that hones in on genetic clues for diagnosing or treating the disease.

Luis Diaz, one of the study's co-authors, is with us. He's an associate professor of oncology and director of the Swim Across America Laboratory at Johns Hopkins Kimmel Cancer Center in Baltimore. He joins us today. Welcome to SCIENCE FRIDAY.

LUIS DIAZ: Hello, how are you?

FLATOW: How are you? Tell us what you discovered in the Pap test here.

DIAZ: Yeah, for a while we had been looking at genetic alterations, which are changes that are specific to cancer or pre-cancerous cells, in a variety of different scenarios as a tool to monitor cancer and to detect cancer early. And we primarily had been looking at the blood.

But we were having some brainstorming sessions with some colleagues in our GYN department here and our pathology department, and an idea popped up: Well, what if we looked at Pap smears? Do ovarian cancers shed cells into the female tract through the fallopian tube, through the uterus, and do they collect in the cervix? And likewise do endometrial cancers shed cells into the uterus that are then collected in the cervix, both of which could be collected with a simple Pap smear brush?

And that was really the hypothesis that we assembled. And we then tested it using specific mutations found in those tumors and were surprised by the results.

FLATOW: How good were the results?

DIAZ: Well, you know, when you do science like this and you come up with hypotheses like this one, about 80 percent of the time they fail, about 20 percent of the time they work, but this is one of the few cases where it worked really well. In ovarian cancer we detected about 40 percent of the cases, and in endometrial cancer we detected all the cases we tested.

And equally as important, in normal Pap smears or healthy Pap smears, we found that there were no false positives, so no misdiagnoses in the normal cases that we tested.

FLATOW: So how close then can we - can you say this could become a practical, very easy test to do?

DIAZ: Well, the obvious advantages are that the Pap test is already ubiquitously done on thousands of women every day all around the world. So that part is already part of medical practice. The difficulty now is jumping through the stringent requirements for any screening test.

This is really just a proof of principle. The next steps are going to require hundreds and hundreds of patients to be tested to see if we capture 100-percent sensitivity in endometrial cancer, a moderate to high sensitivity in ovarian cancer, and if we still have a really low false positive rate.

If that is accomplished when we reproduce this with more patients, then we have to conduct a prospective blind clinical trial in healthy women to see if this actually makes a difference in the diagnosis of early cancers and even eventually in survival.

FLATOW: This would be a real boon to cancer detection because some of these cancers don't show up until very late...

DIAZ: That's absolutely true and especially for ovarian cancer, where most cancers are detected or diagnosed at a very late stage, which is one of the reasons it's so deadly. The same goes with endometrial cancer. It's typically diagnosed because of a symptom of abnormal uterine bleeding in a post-menopausal woman. Even though that is its normal heralding sign, we oftentimes don't detect it early enough, and there's still about 8,000 deaths a year from that cancer.

But our hope is, is that this will continue to move forward, the stringent next steps, and that eventually it'll get to patients.

FLATOW: Are there any dangers that detecting mutations that are not cancerous and giving you a false positive?

DIAZ: That's a great question. I think that there are two issues. One is that if we detect mutations, is that always cancer? And by definition, we've - we and several other millions of people have done studies or thousands of people have done studies on different cancers and found that these cancers by definition are only in the tumor and not in normal cells.

Now, that is kind of a built-in safety valve. That gives us some reassurance that if we find a mutation, it's probably cancer. Now, the other issue is what if you do find a cancer, a mutation, and let's say there is a cancer - will that cancer ever progress? And we see this often in the debates with prostate cancer.

You may detect a cancer, but is it the cancer that will remain dormant forever, or is it the cancer that will grow up and eventually become lethal? And those are questions that are beyond the scope of the screening test and really speak more to the biology of the cancer.

FLATOW: It would seem like something like this, which could be so useful, could be put on a fast track to getting okayed. Is that possible?

DIAZ: You know, that's a good question. However, we still have to wait for time to pass when you do this in a healthy population to see if you impact overall survival over time. You know, I think there's a lot of very good tests out there that can detect things, but whether or not they're going to change the eventual outcome for the patient oftentimes can be challenging.

But I agree with you: If there were a fast-tracked way to get this to patients, that would be ideal.

FLATOW: All right, I'm going to ask you a sneaky question now. If somebody is doing a Pap smear, you know, a physician or a laboratory, could they on their own, without this being, you know, a sanctioned test, do the test themselves?

DIAZ: The technology around this test is specialized. What would need to happen is you'd have to have a digital genomic approach, which isn't readily available to most physicians, and there are a handful of labs around the world that can do this type of analysis.

But yeah, it's always possible to do that, and what a doctor or what a researcher couldn't say is what is the level of certainty around any result that was achieved? And that's why we need to do much larger studies with thousands of women.

FLATOW: And they're going to be beginning soon?

DIAZ: Yeah, the next step right is to reproduce our results in hundreds of women with ovarian and endometrial cancer and hundreds of Pap smears from women without disease to ensure that we have a robust sensitivity, and we have very, very low false positives.

FLATOW: Dr. Diaz, thank you for taking time to be with us today. Good luck to you.

DIAZ: Thank you.

FLATOW: Luis Diaz, one of the co-authors of a paper published in Science Translational Medicine. He's associate professor of oncology, director of the Swim Across America Laboratory at Johns Hopkins Kimmel Cancer Center in Baltimore. Transcript provided by NPR, Copyright NPR.