The Pap test, also called a Pap smear, detects changes in the cells of a woman's cervix. The test has been used successfully to routinely screen for pre-cancerous changes and to detect cervical cancer in the earliest stages when it is most treatable. The sample is typically collected during a pelvic exam when the health care practitioner uses a specialized stick or brush to scrape a few cells from the cervix. A laboratorian examines the cells under a microscope for signs of infection, abnormal cells, or cervical cancer.
Now, a new study published in the January issue of Science Translational Medicine suggests that cervical samples collected during Pap smears contain DNA that can be evaluated for genetic changes caused by both ovarian and endometrial cancers. While this technique needs years of additional testing to see if it can accurately detect the cancers, it would be a very significant advance if future trials are successful. Currently, there are no routine early-detection tests available for identifying the two cancers in average-risk women, and both cancers are often detected at a late and hard-to-treat stage.
According to the Centers for Disease Control and Prevention, all women are at risk for ovarian cancer, but older women are more likely to get the disease. About 90% of women who get ovarian cancer are older than 40 years of age, with the greatest number age 55 years or older. The American Cancer Society estimates that in 2013, 22,240 new cases of ovarian cancer will be diagnosed in the U.S. and 15,500 women will die of the disease. The mortality rates for ovarian cancer have not improved in forty years, according to the Ovarian Cancer National Alliance.
Endometrial cancer, cancer of the uterine lining, is the most common cancer of the female reproductive organs. The American Cancer Society estimates that 49,560 new cases will be diagnosed in 2013 and 8,190 women will die of cancer of the uterine body, most of which are endometrial cancer. Most cases are found in women aged 50 and over.
Current screening tests for ovarian cancer are available only for women at high risk, such as those with a family history. Options include transvaginal ultrasound (with the ultrasound wand inserted into the vagina) and a laboratory test that measures the level of CA-125 in the blood. For women who have an abdominal mass, doctors may screen for a high level of HE4, a relatively new marker for ovarian cancer. Sometimes, CA-125 is combined with an HE4 test and a risk score called the Risk of Ovarian Malignancy Algorithm (ROMA) is calculated to determine whether the practitioner should refer a patient for surgery to remove and biopsy the mass. Another test, called OVA1, measures the levels of five proteins in the blood and then, based on a software program created by the makers of the test, calculates a score used to determine the likelihood that an abdominal mass is malignant.
Unlike imaging or blood tests, the newly developed genetic test uses samples collected from the cervix for liquid-based Pap tests; after collection, the cervical samples are placed in liquid and sent to a lab for further processing. Instead of examining only the cells in the liquid, the new test evaluates the DNA in the samples and uses gene sequencing technology to look for genetic changes that would only be found in endometrial and ovarian tumors. A similar approach has been used in screening for bladder cancer and colon cancer.
For their study, the researchers, from Johns Hopkins Kimmel Cancer Center, used Pap specimens to test for genes that are commonly mutated in ovarian and endometrial cancers. They tested for these mutations in samples from patients in early stages of cancer in 24 endometrial and 22 ovarian cancers. They found the mutations in 100% of the endometrial cancers and 40% of the ovarian cancers. When they tested 14 samples from women with no cancer, there were no false positives. Ovarian cancer is so commonly found at the late stage that the researchers say that even finding only 40% of early-stage cancers is very significant.
Testing is continuing on samples from both women with the cancers as well as in healthy women as a control group, and the researchers hope to finish their testing by the end of the year. In combining the new test with a traditional Pap smear, it may eventually become possible to effectively screen for three major cancers affecting women using one sample.
However, it could take years for safety and clinical testing to be completed before a test would be commercially available. In their report, the researchers say that "although improvements need to be made before applying this test in a routine clinical manner, it represents a promising step toward a broadly applicable screening methodology for the early detection of gynecologic malignancies."
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Kinde I et al. Evaluation of DNA from the Papanicolaou test to detect ovarian and endometrial cancers. Sci Transl Med 2013 Jan 9; 5:167ra4. Available online at http://dx.doi.org/10.1126/scitranslmed.3004952. Accessed March 9, 2013.
(January 9, 2013) Julie Steenhuysen. Fluid from Pap test used to detect ovarian, endometrial cancers. Reuters. Available online at http://www.nlm.nih.gov/medlineplus/news/fullstory_132941.html through http://www.nlm.nih.gov. Accessed March 9, 2013.
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