Recognizing Ovarian Cancer Symptoms Could Help Reduce Misdiagnosis and Late Detection

Recognizing Ovarian Cancer Symptoms Could Help Reduce Misdiagnosis and Late Detection

Ovarian cancer is the most deadly of gynecologic tumors. For the past 25 years, scientists have tried to identify a screening test to detect ovarian cancer in its earliest stages, when the chance of cure is high. Unfortunately, multiple clinical trials with hundreds of thousands of participants have failed to identify an effective way to screen for ovarian cancer.

Fewer than 40% of those diagnosed with ovarian cancer are cured, and approximately 12,810 people in the U.S. die from the disease every year. In fact, the U.S. Preventive Services Task Force gave ovarian cancer screening a grade of D in 2018, meaning it recommends against periodic screening because it doesn’t improve survival and can prove harmful to patients.

Because no effective screening test currently exists, 70% of people with ovarian cancer are diagnosed at advanced stages, when chances of cure are poor. Around 60% to 90% of people with stage one or two cancer that stays around the ovaries and pelvis are disease-free five years after diagnosis, compared with only 10% to 40% of those with stage three or four cancer that has spread through the abdomen and beyond.

But even those with advanced disease have a higher chance of being cured if complete surgical removal is still possible. This makes early diagnosis all the more important for overall survival.

Without screening tests, many physicians wrongly assume that early diagnosis for ovarian cancer isn’t possible. As a gynecologic oncologist who treats hundreds of ovarian cancer patients each year, I was frustrated by these late diagnoses, and wondered if better recognition of its symptoms could help clinicians and patients identify ovarian cancer earlier.

Detectable symptoms

Ovarian cancer has historically been called a “silent killer,” because clinicians thought its symptoms were undetectable. Patients were often diagnosed so late that doctors thought nothing could be done.

But there have been many studies over the past 20 years demonstrating that ovarian cancer does have early warning signs. My colleagues and I conducted one of the earliest studies in 2000. Our survey of 1,700 people with ovarian cancer found that 95% of patients reported noticeable symptoms three to 12 months before diagnosis. The most common symptoms were pain in their pelvis and abdomen, increased frequency and urge to urinate, difficulty eating or feeling full quickly, and bloating or abdominal distension.

Importantly, people with both advanced- and early-stage disease reported similar types of symptoms. Subsequent studies from multiple researchers further confirm that patients with even early-stage ovarian cancer experience frequent symptoms.

We also found that providers often misdiagnosed ovarian cancer as another condition. When we asked patients what their doctors told them was the cause of their symptoms, 15% had their symptoms attributed to irritable bowel disease, 12% to stress, 9% to gastritis, 6% to constipation, 6% to depression and 4% to some other cause. Thirty percent were given treatment for a different condition. And 13% were told there was nothing wrong.

One major issue has been distinguishing ovarian cancer symptoms from those of common gastrointestinal and urinary conditions. In another study, my team and I found that patients with ovarian cancer have symptoms with a recent onset and occur more than 50% of the month.

To facilitate early detection of ovarian cancer, my team and I compared the symptoms ovarian cancer patients experienced with those of patients without ovarian cancer. We developed an index that identified six important symptoms of ovarian cancer: bloating, increased abdominal size, feeling full quickly, difficulty eating, pelvic pain and abdominal pain. Symptoms needed to occur more than 12 times a month but to have lasted for less than a year.

Based on these criteria, our index was able to detect ovarian cancer in 60% to 85% of the patients in our study, a range similar to that achieved through diagnostic blood tests for ovarian cancer.

Preventing ovarian cancer

While early detection is important, there are also prevention strategies that can help reduce the risk of developing ovarian cancer.

If you have a family history of ovarian cancer, inform your doctor, who may recommend genetic testing to fully determine your risk, or prophylactic surgery to prevent the development of cancer.

Oral contraceptives, tubal ligation (or surgery to close the fallopian tubes), pregnancy and breastfeeding all reduce the risk of ovarian cancer.

Finally, up to 70% of ovarian cancers may arise from the fallopian tubes. Removing the fallopian tubes at the time of another surgery may be another option to help reduce the risk of ovarian cancer. This should be done only if you do not plan on becoming pregnant in the future.


Women with genes for endometriosis have higher risk of ovarian cancer

Women with genes for endometriosis have higher risk of ovarian cancer

Researchers find odds of having ovarian cancer up to 2.6 times higher for women carrying genetic risk factors for endometriosis. These women also have a higher risk of developing certain ovarian cancers. A study of genetic markers in nearly 15,000 women with endometriosis and more than 25,000 women with ovarian cancer has found what researchers say is a causal link between the two conditions.

“We have estimated that the odds of having ovarian cancer over a lifetime is up to 2.6 times higher for women carrying genetic risk factors for endometriosis,” said the study’s lead author, Dr Sally Mortlock of the University of Queensland.

The genetic link was specific to certain kinds of epithelial ovarian cancer – the most common category, which accounts for an estimated 90% of cases.

Endometriosis – a condition in which the tissue similar to the lining of the uterus grows outside the uterus – affects an estimated one in 10 women of reproductive age.

“Endometriosis affects as many women as diabetes and asthma yet it has not received the same level of attention or funding, leaving women to suffer in silence,” Mortlock said. Mortlock emphasised that while there was a “significant overlap in genetic risk factors” between the two conditions, the overall risk for developing ovarian cancer was still low. She said having endometriosis increased the risk of developing ovarian cancer to one in 55, compared with an estimated ovarian cancer risk of one in 76 women generally.

“We explored specific areas of DNA that increase the risk of both diseases,” Mortlock said. The researchers found that women with 27 genetic markers – which have previously been strongly linked to endometriosis – were also more likely to have ovarian cancer. Using a statistical method known as Mendelian randomisation, the team were able to demonstrate a causal genetic link, and establish “directionality from endometriosis to EOC [epithelial ovarian cancer] risk rather than vice versa”.

“Some of these genes have important roles controlling the ability of our cells to adhere, or stick, to each other and respond to hormones,” Mortlock said. “This gives us clues that these pathways might be important in disease development and progression.” The identified genes could be used as future drug targets to treat both conditions, she said.

Tracy O’Mara, an associate professor at the QIMR Berghofer Medical Research Institute, who was not involved in the study, said the research demonstrated a causal relationship between the two conditions, which have previously been linked in epidemiological studies. “The relationship between endometriosis and ovarian cancer has [previously] been looked at observationally,” O’Mara said. “It’s nice that they’ve used these genetic techniques … it really shows the shared biology between the two.”

One limitation of the study is that its DNA data only included women of European ancestry. “Whether the results can be extrapolated to other ethnic groups is something that would need to be looked at as well,” O’Mara said. The research was published in the journal Cell Reports Medicine.

Scientists at Yale School of Medicine design a virus to treat ovarian cancer

Scientists at Yale School of Medicine design a virus to treat ovarian cancer

Scientists at Yale School of Medicine design a virus to treat ovarian cancer

A new Yale study showed that certain genetically modified viruses can cure ovarian cancer in mice. It may be of use in the treatment of ovarian cancer in humans.

Researchers at the Yale School of Medicine have tested a chimeric virus — containing genes from two different viruses — that can selectively infect and kill ovarian cancer cells in mice. Their findings represent a potential breakthrough in the long-term treatment of ovarian cancer in humans. The study was published in the journal Virology on Nov. 12, two weeks after the death of the paper’s lead author Anthony Van den Pol, former professor of neurosurgery and psychiatry at Yale.

“Every year, around 20,000 women are diagnosed with ovarian cancer, which is a smaller number compared to cancer types such as breast cancer,” said Gil Mor, the scientific director of the C.S. Mott Center for Human Growth and Development at Wayne State University and a co-author of the paper. “However, unfortunately only around 4,000 of those women can survive the disease.”

The main reason behind the lethality of ovarian cancer is the lack of treatments preventing the recurrence of the disease. In 80 percent of cases, patients who respond positively to chemotherapy still experience a return of the disease, according to Mor. He explained that once the cancer comes back and begins to spread, there is little that doctors can do.

The inspiration for the study was born out of a collaboration between Van den Pol and Mor many years ago, when they worked in adjacent labs at the Yale School of Medicine. Van den Pol, a research scientist in the Neurosurgery Department, had concentrated his research on the long-term treatment of brain tumors. Mor, on the other hand, had been working on treatments for ovarian cancer. The two scientists decided to collaborate to find an alternative treatment for ovarian cancer through oncolytic viruses, which selectively infect and kill cancer cells.

In the experiment’s in vitro phase, in which the research takes place in laboratory tubes or petri dishes without a living component, researchers made a virus called Lassa-VSV in the laboratory. Lassa-VSV consists of three parts: the Lassa virus, the vesicular stomatitis virus, or VSV, and a fluorescent label to facilitate tracing, according to Nazli Albayrak, a scientist who was involved in the in vitro phase. During this phase, the team infected different ovarian cancer cell lines, eventually choosing the ones that were infected most frequently to proceed with the research.

Then, after deciding on the cell line, the team injected tumor cells into the bodies of the mice, the paper explains. As the tumor cells began to replicate, the team then injected the Lassa-VSV virus into the tumor clusters. They observed that the virus infected the tumor cells very effectively yet did not harm the healthy cells that were present in other parts of the mice.

In gynecologic oncology, patients who are suffering from ovarian cancer are currently provided with chemotherapeutic agents after their surgeries. However, as Mor and Albayrak also mentioned, chemotherapeutic agents are not a cure for these patients.

This observation prompted the researchers to compare the effectiveness of chemotherapeutic agents and the Lassa-VSV chimeric virus in clearing tumor cells from the mice’s bodies. They found that the virus was able to get rid of more cancer cells than the chemotherapy treatment and do so without harming healthy mouse cells. Albayrak also noted that the mice treated with the Lassa-VSV virus lived approximately four times longer than those treated with chemotherapeutic agents.

Vaagn Andikyan, assistant professor at the School of Medicine who also works in gynecologic oncology, said that this form of treatment could be more effective in treating cancer in humans and be a prevalent option in the future.

“It is a very intriguing, very unique approach to ovarian cancer, and this approach may be applicable for several other malignancies,” Andikyan said.

Andikyan works with the standard treatment of ovarian cancer, a field that is rapidly changing through new drugs and new treatment procedures. He said that this paper’s approach to treating ovarian cancer is promising to him.

According to Mor, if the clinical phases — in which human subjects are involved — prove to be successful, many people can benefit greatly from the researchers’ discovery. This approach may even lead to the discovery of a vaccine against tumors and even in different cancer types, Andikyan said.

Van den Pol died on Oct. 28, the day on which the team’s paper was accepted to Virology, a pioneer journal in the field. Mor said that the team would miss Van den Pol and continue to honor him in their future research. Albayrak and Mor noted that they did not know Van den Pol had a condition until receiving news of his death.

“He was a very private person, and we knew that he did not feel well, but we never realized the magnitude of his disease,”  Mor said.

The team and Van den Pol’s colleagues at the Yale School of Medicinewere saddened by the news, yet the team is hopeful about the discovery they recently made and will continue to include Van der Pol as an author in their future studies. Ovarian cancer is the fifth-most deadly cancer among women, according to the American Cancer Society.


New technologies aim to improve ovarian cancer detection

New technologies aim to improve ovarian cancer detection

Encouraging trends abound in the management of ovarian cancer. As rates of ovarian disease continue to decline, there has also been a notable increase in tools for detecting it earlier in its course.

To better understand these developments, Medscape recently reached out to Rebecca Stone, MD, an ovarian cancer expert and associate professor of gynecologic oncology at Johns Hopkins University School of Medicine, in Baltimore, Maryland. This interview has been edited for length and clarity.

Medscape: There has been a decline in the rates of ovarian cancer in recent years. What are the possible causes of this?

Dr Stone: The number of new cases in the United States has actually been declining over the past two decades. This is thought to be attributable to the increased prescribing of oral contraceptive pills in the late 1990s and the uptake of preventive measures, such as risk-reducing gynecologic surgery for women with genetic predisposition to ovarian cancer, as well as opportunistic salpingectomy in the general population. Opportunistic salpingectomy was introduced about 10 years ago. It is a surgical means for primary prevention of tubo-ovarian cancer by removing both fallopian tubes at the time of elective surgery for women who have completed childbearing or in lieu of “tying the tubes” for women who desire permanent surgical sterility.

What can you tell us about a recent study suggesting that high-grade serous epithelial ovarian cancer may be detected earlier in the course of the disease by testing for TP53 clonal variants in DNA from Papanicolaou (Pap) tests performed during cervical cancer screening?

The idea here is that early mutational events that ultimately result in the development of epithelial ovarian cancer can be detected by performing gene sequencing on genetic material collected at the time of routine Pap smear screening done for cervical cancer. Pap tests are known to contain cells and genetic material shed from the fallopian tubes, where the precancerous lesions thought to give rise to epithelial ovarian cancer, predominantly serous epithelial ovarian cancers, start.