Ask the Doctors: Promise in diagnosing early-stage cancer

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Q: I recently read that a modified Pap smear has the potential to show early warning signs of ovarian and endometrial cancers, as well as cervical cancer. How accurate is this test, and when might it be available?

A: An almost all-purpose test is a tantalizing prospect. Already, the Pap smear and HPV testing are crucial screenings in the diagnosis of cervical cancer and have led to a significant decline in death rate from the disease. Yet thus far, screening tests for endometrial (uterine) cancer and ovarian cancer have not been promising. Endometrial cancer and ovarian cancer combined still claim the lives of about 25,000 women in the United States per year because such cancers are often found only after they have spread to other portions of the body. A screening test to find these cancers could dramatically reduce those numbers.

Such a test could be available in the relatively near future. A greater understanding of the gene mutations involved in these two cancers have spurred some scientists to propose a simple technique to find these mutations using DNA testing of the fluid obtained through the Pap smear. A study published in March assessed the technique's ability to detect such mutations in 382 women diagnosed with endometrial cancer, 245 women with ovarian cancer and 714 women without cancer.

Researchers looked for mutations within 18 genes and also for an abnormal number of chromosomes. The technique, called "PapSEEK," positively identified 81 percent of women with endometrial cancer, including 78 percent of those with early-stage endometrial cancer. However, it identified only 33 percent of women with ovarian cancer, including only 34 percent with early-stage disease.

In an attempt to improve these numbers, researchers took samples from farther within the uterus in a subset of patients. The test then positively identified 93 percent of women with endometrial cancer, and 45 percent of those with ovarian cancer.

The researchers also tested a subset of patients with ovarian cancer using PapSEEK and a blood test to detect circulating tumor-specific DNA. The positive rate then increased to 63 percent for ovarian cancer, including 54 percent with early-stage ovarian cancer. It's an improvement, but a lot of ovarian cancers would still be missed.

On the plus side, the rates of false positives were low with these tests. In the women without cancer, the rate of false positives was between zero and 1 percent.

Note that this was a retrospective study, meaning that the test was conducted among women who had already been diagnosed with cancer. It's unclear how well the test would work as a screening that could affect the course of the disease. A large screening study is needed to help us understand the true potential benefits of the test.

No doubt about it, however, the results are encouraging, especially as a way to detect endometrial cancer when used on samples taken from farther within the cervix and to detect ovarian cancer when used with a blood test.

Due to the need for more assessment, the test may not be available for several years, but it's good to know that our increased ability to conduct DNA testing is likely to help us, ultimately, catch these cancers early enough to save more lives.



Robert Ashley, M.D., is an internist and assistant professor of medicine at the University of California, Los Angeles. Send your questions to askthedoctors@mednet.ucla.edu, or write: Ask the Doctors, c/o Media Relations, UCLA Health, 924 Westwood Blvd., Suite 350, Los Angeles, CA, 90095. Owing to the volume of mail, personal replies cannot be provided.

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