Screening for Ovarian Cancer: What you need to know

Who this is for:  every woman, especially those with a family history of reproductive system cancers.

What you’ll learn: current screening test choices and upcoming advances in detection.

Average read time:  4-7 minutes

     Since the introduction of the Pap test, the mortality of cervical cancer in screened populations has been reduced by more than 75%.  In contrast, deaths from ovarian cancers have not substantially decreased during that same time period. This is primarily due to the fact that ovarian cancers are typically not diagnosed until they are far advanced, where survival rates are considerably lower.   As a result, in the United States about 15,000 women are expected to die each year from ovarian cancers. The mortality associated with undetected ovarian cancer has made the development of a more effective screening tool a high priority.

         So the search is on to find a screening test that would help detect ovarian cancer early, much like prostate-specific antigen tests with prostate cancer or mammograms with breast cancer.  Screening tests are those done on symptom free individuals, usually at prescribed ages and intervals.

     Currently the best available screening tests for ovarian cancer, the CA 125 blood test and the transvaginal sonogram give too many false-positives (where the test says you have cancer, but the result is wrong-you don’t have it), so neither are currently recommended as routine screening tests. It is a reasonable concern that generalized screening may cause more harm than good, as false-positive tests may call for further evaluation by further imaging, laparoscopy or exploratory laparotomy, all of which may have unintended complications and additional costs.

     Because of these concerns, major organizations that advise on medical screening tests for women, such as the U.S. Preventative Services Task Force, the American College of Obstetricians and Gynecologists, the American Cancer Society and the National Comprehensive Cancer Network do not recommend routine screening for ovarian cancers in the general population.

     Keep in mind that such recommendations are good for public health advice to the masses, but the specific choice of medical evaluation for your own situation should be made on an individualized basis, in consultation with your personal physician. 

      The focus of this article is to review the current screening tests that are now available, and to discuss the next generation of screening, the Pap Gene test, which is now on the near horizon.

Who should be screened for ovarian cancer?

Both the CA-125 and transvaginal sonography (TVS) are recommended for women who have a family history of ovarian cancer, or who experience symptoms such as abdominal bloating, pain, change in bowel habits or unusual fatigue. It can vary tremendously among individuals as to how far a tumor has to progress before such symptoms are evident.   Unfortunately, even when these symptoms are classic and persistent, all too often they may be ignored and even after medical evaluation they may be dismissed as menstrual cycle variations or as gastrointestinal in origin.

Additionally, for patients with a hereditary predisposition to ovarian cancer, and having mutations in the BRCA gene, it is recommended that screening with TVS and serum CA-125 should be as often as every six months, starting at a relatively early age.  Current screening methods include :

The CA-125 blood test

     CA-125 is a glycoprotein expressed in some ovarian cancer patients with early-stage disease and in some cases before clinical diagnosis.  This protein exists in greater concentration in cancerous cells. Though a high count of this protein may help to identify ovarian cancers, premenopausal women may also have an elevated CA-125 due to benign conditions that are unrelated to ovarian cancer.  Uterine fibroids, liver disease, inflammation of the fallopian tubes, endometriosis, ovarian cysts and other types of cancer can raise a woman’s CA-125 level, often causing a false positive test for ovarian cancer.

     Although the CA-125 blood test is more accurate in postmenopausal women, it is not a reliable early detection test for ovarian cancer.  Also, there can be false negatives, where in about 20 percent of advanced stage ovarian cancer cases and 50 percent of early stage cases, the CA-125 is not elevated even though ovarian cancer is present. These false negative rates are reduced when the CA-125 blood test in combination with a transvaginal ultrasound.

     The CA-125 blood test has its greatest utility in evaluating a diagnosed ovarian cancer’s response to treatment. And after initial treatment, this test is also used as a monitor for evidence of recurrence.

Transvaginal Sonography

     A transvaginal sonogram (ultrasound) is a test used to examine the reproductive organs. To administer the test, the doctor inserts a probe into the vagina. The probe sends off sound waves which reflect off body structures. The waves are then processed by a computer that turns them into a picture.  The process is similar to the external obstetrical ultrasound used to monitor a pregnancy, except that the probe in TVS is internal.

     Although TVS can visualize the ovary, it can reliably only detect larger tumors and cannot always distinguish benign from malignant tumors.

Several clinical screening trials using a combination of serum CA-125 and TVS have been conducted, but none have shown a defined survival benefit in otherwise healthy individuals not having symptoms.

The Pelvic Exam

     A pelvic exam should be a part of a woman’s regular female health exam. This exam requires the doctor to place one or two fingers into a woman’s vagina with the other hand over her abdomen to feel the size, shape, and position of the ovaries and uterus. Ovarian cancer is rarely detected in a pelvic exam and if it can be felt manually it is usually at an advanced stage by that time.  This is yet another reason we are looking for better screening tools

PapGene testing:  Not yet, but soon

     As you may be aware, the last 10 years has seen dramatic progress in the analysis of genetic information.   Some of this technology to decode the human genome is now routinely available to physicians, and even to the general public through companies like 23andme.   Currently the genomes (genetic codes) of more than 50 types of tumors had been sequenced, and researchers are now working to take advantage of this information.

     An article in the January 9, 2014 journal Science Translational Medicine: Integrating Medicine and Science titled “Evaluation of DNA from the Papanicolaou Test to Detect Ovarian and Endometrial Cancers” (found at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3757513/) is an example of this research in action.  It discusses the PapGene test, which is a highly sensitivity approach to the detection of cancer-specific DNA mutations.

     The key finding in this paper is that diagnostically useful amounts of cell fragments from endometrial and ovarian cancers are present in the cervix and can be successfully detected through genetic sampling and recognition.

     Since the routinely screened Pap test can contain cells shed from the ovaries or endometrium, it has been theorized that cancer cells arising from these organs could be present in that same cervical fluid. Using cervical fluid obtained during routine Pap tests, researchers at the Johns Hopkins Kimmel Cancer Center are in the process of developing a test for early detection of ovarian and endometrial cancers. From the ovarian and endometrial cancer genome data, they identified 12 of the most frequently mutated genes in both cancers and then developed the PapGene test to amplify these genes and then detect them in the Pap sample.

     In the pilot study described in this article, this PapGene test accurately detected all 24 (100 percent) endometrial cancers and nine of 22 (41 percent) ovarian cancers.  As the endometrial tissue is closer to the cervix than the ovaries are, one is more likely to find more endometrial than ovarian cancer tissue fragments on any given Pap test sampling.

     Additionally, no healthy women in the control group were misclassified as having cancer; a zero false positive rate.  The hope is that genomic-based tests could help detect ovarian and endometrial cancers early enough to cure more of them. The fact that the Pap Gene can be done by batch testing, rather than requiring microscopic evaluation by a trained cytopathologist may also help lower what will be an initially higher cost per test over time, as well.

     The investigators appropriately noted that larger scale studies are needed before clinical implementation can begin.  They also expressed hope that the test has the potential to pioneer other genomic-based cancer screening tests.

     The investigators’ next steps include applying PapGene on more samples and working to increase the test’s sensitivity in detecting ovarian cancer.  “Performing the test at different times during the menstrual cycle, inserting the cervical brush deeper into the cervical canal, and assessing more regions of the genome may boost the sensitivity,” says Chetan Bettegowda, M.D., Ph.D., assistant professor of neurosurgery at Johns Hopkins.

     While the routine availability of this testing is many months, or even years away, it sets the stage for a simpler and more effective way for your ‘yearly exam’ to get the jump on some of the most feared female cancers.

What this means to you

     Ultimately, your well being today and your eventual health quality over the years to come; as much as it can be controlled, is up to you.   The reason you read an article like this is so that you can have the information to make wise health decisions, and to be appropriately proactive in your choices.  Nobody knows your body as well as you do. Your doctors and the health care system can assist and extend your self care efforts, but it cannot replace them. 

Some actions you should take include :

   -If you have risk factors such as a family history of a disease or cancer, let your doctor know. 

   -If you have potentially adverse habits like smoking, drinking alcohol, a sedentary lifestyle or a fast food or sweets loaded diet, please strongly consider changing your choices for the better. 

   -If you have persisting symptoms, like the ones reviewed earlier in the article, pay attention and discuss the details with your physician. 

   -Get periodic screening health exams and tests that are appropriate to your age and history.  At the minimum, a pelvic exam and pap test should be performed every three years.

   -If your health provider doesn’t review your concerns and the reasonable options with you, be persistent enough to consider a second opinion.

     The tools to both prevent disease, and to catch a cancer early enough to treat it successfully are there for you, and getting better all the time.  Know yourself, know your options and when indicated, take action.   “Vision is not enough, it must be combined with venture. It is not enough to stare up the steps, we must step up the stairs.” ~ Vaclav Havel