Nearly All of Us Have a Virus that Causes Cancer

There's a virus that the vast majority of adults have, that's been around for more than half a century, that lies dormant in our systems—and then, for a minority of people, triggers the development of cancer. Last week, an international team of researchers identified a gene mutation that might cause susceptibility for this last unlucky turn of events. While the virus, called Epstein-Barr (EBV), was discovered more than half a century ago, researchers are only now making progress in understanding it—and beginning to make strides towards stopping the pathogen that causes an estimated 143,000 cancer deaths every year.

The EBV-cancer connection was discovered in 1958 by a surgeon named Dennis Burkitt who noticed a specific type of cancer that was common in young children in central Africa (it was later named Burkitt's lymphoma). More recently, EBV has been found to cause nasopharyngeal cancer (a rare head and neck cancer that occurs in the cavity behind the mouth), other lymphomas (such as Hodgkin's lymphoma, non-Hodgkin's lymphoma, and T-cell lymphoma), some cases of stomach (or "gastric") cancer, and post-transplant lymphoproliferative disease (PTLD), a serious complication following an organ transplant.

"Ninety-five percent of adults have EBV—it's living happily in our throats and our B cells (a type of white blood cells), and it's not causing problems for most people," explains Patrick S. Moore, director of the cancer virology program at the University of Pittsburgh Cancer Institute. In fact, many people don't ever realize they've been infected with the virus because they don't experience symptoms. "Most of us have developed systems to keep that virus in check," Moore adds. But some people can't suppress the virus, in which case it can harm their health. Among those in the latter camp are people experiencing immunosuppression from a genetic abnormality, as the new study suggested, from untreated AIDS, or from anti-rejection medications taken after a solid organ transplant or stem cell transplant.

Aside from these high-risk groups, "it's really hard to know who's going to be affected by EBV and who isn't," says Shikha Jain, a hematologist and oncologist at Northwestern Medicine in Chicago. "Most people get infected with EBV as children, and once you have it, the virus persists for life but it can lie latent, without causing any symptoms." Even when it's in a state of suspended animation, however, there is always the possibility that it can become reactivated and cause problems in the future.

Normally, EBV stays inside B cells, where it expresses proteins that can cause cells to replicate and expand, and the immune system keeps that replication in check. But under certain circumstances, such as when the immune system is compromised for one reason or another, the pathway to halting rampant proliferation is lost, which means the cells will keep growing and dividing, and the EBV will get transferred from B cell to B cell and the proliferative state can lead to cancer. "The more a cell proliferates the greater the chance of a mutation occurring and the more mutations that occur, the greater the chance of it turning into cancer," explains Ezra Cohen, a professor of medicine at the Moores Cancer Center, UC San Diego.

Still, the reality is that "the majority of people who have EBV are not going to get [an EBV-related] cancer," Jain notes. Other genetic or environmental factors (such as diet or smoking) are often needed to increase a person's susceptibility to one of these cancers.

Different EBV-related cancers are more common in varying parts of the world. It probably has to do, in part, with the genetic factors in the host, which allow the virus to live, Cohen says, but it also may be that certain strains of the virus that are more damaging are more prevalent in some places than others. For example, EBV-related nasopharyngeal cancer is more common in Southeast Asia. In 2015, Cohen treated a 41-year-old woman from China who had developed a tumor in her nasopharyngeal cavity that was causing changes to her vision because of its location. Radiation therapy was used to destroy the tumor, and the woman's vision returned to normal.

By contrast, Burkitt lymphoma, a form of non-Hodgkin lymphoma, has a higher prevalence in certain parts of Africa. Meanwhile, in the US and Western Europe, EBV-related gastric (stomach) cancers, diffuse large B-cell lymphomas, and PTLD are more prevalent.

Despite the potential cancer connection, experts don't recommend that people routinely get tested for EBV, because the "results won't change anything, and this will only increase anxiety and stress unnecessarily," Jain says. If you have EBV, nothing specific can be done to mitigate the potential risk of developing an EBV-related cancer (aside from the usual health-protective strategies like eating a healthy diet, exercising regularly, and getting enough sleep), Jain says.

But if someone does develop a type of cancer that's known to be associated with EBV, doctors will check for EBV; the same is true if someone is undergoing immunosuppression or is a candidate for a bone marrow transplant. In addition, doctors "use the presence of EBV DNA in a patient's blood [after treatment] as a marker of how successful treatment is," Cohen says. "The higher the level is, the worse the prognosis is. It should be nearly undetectable after treatment." Indeed, a 2016 review of 23 studies found that when patients with nasopharyngeal cancer had high EBV DNA levels after they completed treatment, their prognosis was poor. Fortunately, "we can cure most of these [EBV-cancer] patients," Cohen says.

In some instances, the connection between EBV and certain forms of cancer may even inform treatment. With EBV-associated lymphoma, for example, a drug called rituximab is used "because it directly works against the Epstein-Barr virus," Jain explains. In a 2013 study in Greece, researchers examined the effects of rituximab-based immunochemotherapy on 44 patients with low-grade B-cell lymphoma and found that after three monthly cycles of the drug, only one out of 17 patients who were EBV-positive before the study still tested positive for EBV after the treatment. The same drug is often used for people who have EBV-associated PTLD. Not long ago, Jain treated a Chicago police officer who developed PTLD after having a kidney transplant; after receiving rituximab for four months, the mass in his abdomen shrank dramatically and he was feeling great again.

The hope is that some day EBV-related cancers could be prevented with a vaccine that prevents infection with the virus, much like the HPV vaccine has been found to help prevent cancers such as cervical cancer. "Scientists in this field would love to see an EBV vaccine," Moore says. "We could vaccinate children as well as adults who are EBV-negative and at risk for transplantation"—which could prevent the vast majority of the 143,000 annual deaths that occur from EBV-related cancers.

The holy grail would be to develop a therapeutic vaccine that would stimulate the immune system in someone who already has an EBV-induced cancer to recognize these latent EBV-expressed proteins and kill them to fight the cancer, Moore adds. The problem is, right now, funding for research on virus-induced cancers including Epstein-Barr is fairly scarce, Moore says. "This is an underappreciated but easily treatable problem in the scientific world. Until people recognize this connection, not a lot of progress can be made."