“All cancers are alike but they are alike in a unique way.” - Siddhartha Mukherjee, The Emperor of All Maladies: A Biography of Cancer
“. . . as in drug discovery and development, we must all be mindful that an approach that works in one community may not work in another. That’s why it is so important to keep patients at the center of all work on cancer. . .At the end of the day, this work is about more than bringing a new lifesaving drug to market or extending the reach of high-quality cancer care. It is about giving people hope and the expectation of a healthier life —two truly wonderful gifts.”
- Julie L. Gerberding, M.D., former Director, Centers for Disease Control and Prevention
Cancer is the second most common cause of death in the U.S., exceeded only by cardiovascular disease. While the cause of many cancers remains unknown, it is known that there are microbes that directly cause certain cancers. These carcinogenic or oncogenic microbes are the focus of this Germ Gem post.
Worldwide impact of carcinogenic microbes. In February 2020, in the article “Global burden of cancer attributable to infections in 2018: a worldwide incidence analysis,” the Lancet published the results of a comprehensive assessment of cancers caused by infectious pathogens. The authors found an estimated 2.2 million infection-attributable cancer cases, or about 13% of all cancers globally. Eastern Asia and sub-Saharan Africa had the highest rates of age-standardized incidence of infection-associated cancers while Europe and Western Asia had the lowest. China accounted for a third of worldwide cancer cases attributable to infectious agents. The main value of the Lancet report is to help direct resources globally to cancer programs that target infectious agents. It also provides an excellent overview of microbes that cause cancer, some of which can be prevented with vaccines.
Carcinogenic pathogens. The Lancet study found four carcinogenic pathogens to be the most impactful. The bacterium Helicobacter pylori, a cause of stomach cancer, led the list. (H. pylori is also the most common cause of peptic ulcers and gastritis.) Improved sanitation and antibiotic treatment, however, can control this bacterium thereby preventing it from causing cancer.
Human papilloma virus (HPV), a cause of cervical, anal and oropharyngeal carcinomas, and hepatitis B virus (HBV), a cause of liver cancer, were the next on the list. Both are vaccine-preventable diseases. HBV vaccine—the world’s first anti-cancer vaccine—and HPV vaccine are recommended for all children. We adults in developed countries rarely think about these vaccines and the huge number of deaths they prevent. But the same is not true in the developing world where HPV is still responsible for many thousands of cancer deaths, an estimated 92% of which could be prevented by the HPV vaccine.
Hepatitis C virus (HCV)—a cause of liver cancer—was fourth on the Lancet’s list. HCV also causes acute and chronic hepatitis, ranging in severity from a mild illness to one that is serious and lifelong. Globally, an estimated 71 million people have chronic HCV infection many of whom will develop cirrhosis or liver cancer. While a vaccine is yet to be developed, chronic HCV can be treated with medications, thereby averting the development of cancer.
The authors of the Lancet report also highlighted carcinogenic pathogens that cause lymphomas. These carcinogenic microbes were: HTLV-1 (the cause of adult T-cell leukemia), HCV (a cause of non-Hodgkin’s lymphoma), H. pylori (which in addition to causing stomach cancer, causes gastric lymphoma), and Epstein-Barr virus (EBV), a cause of Hodgkin’s and Burkitt’s lymphoma. EBV is also the cause of infectious mononucleosis, a disease that is most commonly clinically manifested in adolescents and young adults, although most EBV infections are asymptomatic (95% of adults have been infected). Lymphomas caused by EBV are mainly seen in people with a compromised immune system, often due to drugs taken to prevent organ transplant rejection or HIV/AIDS. A vaccine against EBV is in development.
The human microbiome and cancer. One of the most exciting areas of recent research on the gut microbiome (defined as the estimated 40 trillion bacteria that colonize your gastrointestinal tract) is occurring in the field of oncology. A mounting number of studies have linked the composition of the gut microbiota to colorectal cancer, liver cancer, pancreatic cancer, and childhood leukemia. It is hoped that by manipulating the gut microbiome through a procedure like fecal microbiota transplantation these cancers can be prevented, or more effectively treated. Equally exciting is the recent suggestion that manipulating the gut microbiome may also improve the effects of the most promising forms of immunotherapy called “immune checkpoint inhibitors” that release the brakes (i.e., checkpoints) to activate the immune system against highly malignant cancers, such as metastatic melanoma. Similar enthusiasm about improved treatments and prevention is seen among researchers studying the role of the oral microbiome in esophageal and stomach cancers.
Perhaps most amazing of all, however, are recent studies of microbes that live inside tumors (the tumor microbiome). Incredibly, a variety of tumors have been found to harbor bacteria. In May, the journal Science reported the first comprehensive survey of tumor microbiomes. Ravid Straussman at the Weizmann Institute of Science in Israel and his colleagues looked for bacteria in just over 1000 tumor amples collected from people with cancers of the bone, brain, ovary, breast, skin, pancreas, or lung. They found bacteria in tumors from all cancer types. In total, 528 bacterial species were detected in the tumor samples. At this stage, they don’t know why bacteria exist in tumors. But they speculate if bacteria play a role in tumor development, then manipulating the tumor microbiome may open a new avenue for cancer therapy.
COVID-19 plus cancer. While SARS-CoV-2, the coronavirus that causes COVID-19, isn’t a carcinogenic pathogen, COVID-19 is now the third most common cause of death in the U.S. Many reports have surfaced of a higher risk of severe COVID-19 in patients with cancer. For example, in an October 22 report in MedPage, of 89 cancer patients admitted to the intensive care unit at Memorial Sloan Kettering, 32 died (a mortality rate of 36%). Also, it has been reported elsewhere that patients with hematologic cancers, most commonly leukemia and lymphoma, had a higher mortality rate than those with solid tumors, such as lung or breast cancer.
Researchers aren’t yet sure if the high mortality rate of cancer patients with COVID-19 is driven by age, gender, or other comorbidities. Nor is it yet clear whether anticancer treatments play a role in the high mortality. What is entirely clear, however, is that to win the battle against SARS-CoV-2, we need a vaccine. It’s not a matter of if, but when.
