Photo by Robert Hood / Fred Hutch News Service
For as long as humans have walked the earth, we’ve been accompanied by microscopic beings that are part of our bodies but not ourselves. The viruses and bacteria that coexist with humans have shaped who we are, but that doesn’t mean they are all benevolent.
As research presented at this week’s 2017 American Society of Preventive Oncology meeting in Seattle showed, viewing our microbes as wholly good or bad might be an oversimplification.
Dr. Meredith Hullar is a researcher at Fred Hutchinson Cancer Research Center who studies the gut microbiome — the collection of trillions of bacteria that inhibit our digestive tract — and its complex interplay with diet and cancer risk. She spoke at the meeting Monday about her research and that of others who are looking at how gut bacteria can increase or decrease colorectal cancer risk.
Gut bacteria can alter cancer risk up or down
“Gone are the days of one organism, one disease. We’re really looking at how a whole community of microbes influences disease risk,” Hullar said. “For example, scientists are looking at how the metabolism of the microbiome — all of the members of the microbial community — influences its host,” she said. Researchers are exploring questions such as whether the microbiome produces metabolites that promote tumor growth or may prevent cancer.
There are several different types of human bacteria that can directly fuel colorectal cancer risk, Hullar said. Those include the bacterial species Streptococcus gallolyticus and Fusobacterium nucleatum, as well as certain types of E. coli and conglomerate communities of bacteria that form layers in the gut that are called biofilms. All of these microbes act in different ways on the cells that line our gut to increase risk of tumor formation, she said.
But interestingly, many other types of gut bacteria can alter cancer risk — either up or down — through indirect routes that involve what we eat.
Because these bacteria help digest our food, what we eat influences what they excrete in our gut. Some microbial byproducts — such as those produced when processed meat or high-protein foods are digested — increase cancer risk. Compounds formed in the gut by bacteria during the digestion of a high-fiber food — for example, cruciferous vegetables such as broccoli — seem to be linked to a lower risk of colorectal cancer, Hullar said. She and her colleagues are studying the different microbial communities in people with high or low levels of one of those compounds linked to a lower risk of cancer, known as enterolignans. They are now researching whether changing people’s diets changes the amount of enterolignans they produce and how the human cells that line the gut may respond to those compounds in cancer prevention.
Two deadly pathogens
Although these complex bacterial communities seem to have equally complex relationships with cancer risk, there’s at least one bacterium whose link to cancer is somewhat more straightforward. The bacterium Helicobacter pylori — which colonizes in the stomachs of about two thirds of people worldwide — is directly linked to stomach cancer, the fifth most common cancer in the world and the third most common cause of cancer-related death, said microbiologist Dr. Meira Epplein of Vanderbilt University at Monday’s session.
Although eradicating the bacterium may stem stomach cancer, it’s not yet clear who should be targeted, Epplein said. Her team is studying communities in the Southeastern U.S. who have higher than average levels of H. pylori infection.
But even here, the picture is nuanced. Most people infected with the bacterium don’t develop stomach cancer, and H. pylori infection also seems to reduce the risk of a type of esophageal cancer, Epplein said, so more research is needed.
Stopping hepatitis C from turning deadly
Dr. Lesley Miller of Emory University dropped a statistic that she felt hasn’t reached enough of the public — that hepatitis C virus kills more people in the U.S. than any other infectious disease, including HIV. Up to 4 million people in the U.S. are infected with the virus, Miller said, and it’s incredibly deadly. If unchecked, it can lead to cirrhosis and liver cancer, which is very difficult to treat.
But the infection is very treatable if diagnosed early enough, she said. And in 2012, the Centers for Disease Control and Prevention recommended that all baby boomers, the segment of the population that has the most hepatitis-C infections, be screened for the virus. The infection can be cleared with a simple (if expensive) course of oral antivirals before it progresses to cancer.
“It’s really frustrating to see a case of cancer that’s completely preventable, if we could have caught the infection and treated it earlier,” Miller said.
HPV vaccine: some good news, some bad news
Public health researchers from around the country convened at Monday’s meeting to present their latest findings on the HPV vaccine — who’s getting it, who’s not, do parents who decline the vaccine for their children ever change their minds, and is the vaccine doing any good?
The HPV vaccine may be one of the best cancer prevention methods to come onto the market in the past few decades. It’s highly effective at preventing the strains of HPV that cause nearly all cases of cervical cancer and many other anogenital cancers — plus head and neck cancers. The vaccine, which was approved for girls in 2006 and for boys in 2009, works best if people are vaccinated before they’re exposed to the virus. Since HPV is sexually transmitted, that means the vaccine is recommended for pre-adolescent children aged 11-12 — before they’re sexually active. The vaccine is also approved for teenagers and young adults in the U.S. up to age 26. (Children under 14 need just two doses of the vaccine; those 15 and older still need three doses.)
And in countries where most kids get the vaccine, it’s working. In Australia, which has a nationwide vaccination program, cases of genital warts, an earlier sign of HPV infection than the virus-linked cancers, dropped more than 90 percent in young women after the vaccine was implemented. But clinicians and researchers alike have been dismayed by the vaccine’s low uptake rate in the U.S. In 2015, only 42 percent of girls and 28 percent of boys had received the full vaccine series.
Many researchers are trying to boost that number, including some who presented Monday at ASPO.
But the results of their efforts have not always been so easy to understand, they said. Dr. Nora Henrikson of Kaiser Permanente Washington Health Research Institute (formerly the Group Health Research Institute) in Seattle presented results from a study in which parents of unvaccinated children aged 10 and older received a letter with information about the vaccine written by a pediatrician and nurse. Starting when the children turned 11 and were eligible for the vaccine, they also got automated phone call reminders and the option to opt in to a text-reminder system.
Overall, the Kaiser study found a slight boost to vaccine rates, Henrikson said. In surveys, the parents said they liked the mailed information, and 23 percent of those who received a letter and phone-call reminder brought their child in for the first vaccine dose within three months of the reminder, as compared to 18 percent of parents who didn’t get a phone or mail prompt.
Parents with young adolescents who haven’t yet gotten their kids vaccinated aren’t necessarily going to be lifelong vaccine refusers, as Henrikson’s study found. That squares with a study led by Dr. Melanie Kornides from Harvard Medical School, who asked: Do parents who actively refuse the HPV vaccine for their children ever change their minds? Using an online survey, she and her colleagues looked at close to 500 parents of adolescents who were eligible and had access to the HPV vaccine and had refused the vaccine at a well-child checkup. Surprisingly, 45 percent of those parents later changed their mind and said yes to the vaccine. Another 24 percent said they were planning to get their child vaccinated in the coming year.
This is an important message to send to health care providers, Kornides said, many of whom have reported frustrating encounters with parents who refuse vaccination. Previous studies have found that providers spend extra time and resources on these families and the providers report that they feel the time is wasted because they don’t think the parents will change their minds.
But the Harvard study showed not only that close to half of these parents will reverse course, but that they’re influenced by the information they get from their providers. Parents who reported high satisfaction with the provider communication were more than three times as likely to agree to the vaccine later than parents who weren’t satisfied. And providers who brought up the HPV vaccine again in a later visit, even after the parents had already refused, were more than twice as likely to change the parents’ minds.
“Providers really should be bringing the vaccine up again, because many of these people will go on to get it,” Kornides said.
Even though vaccine refusal and the low uptake may be a hard nut to crack, the reasons parents gave for changing their mind were not complex, the researchers found. Close to half of those who changed their mind said it was simply because their child got older. And approximately a third also said learning more about the vaccine and getting good information from their providers influenced their decision to accept vaccination.
Other highlights from the HPV-associated cancers talks included:
- Research from the University of Texas Medical Branch that found cervical-cancer incidence rates have decreased in young women since the vaccine has been implemented in the U.S. Even though this study doesn’t definitively prove that the vaccine is linked to the decrease since the population-wide cancer registry doesn’t track HPV vaccination, it’s an encouraging result that even at low levels of uptake, the vaccine is working as intended, said Dr. Fangjian Guo, who led the study.
- Dr. Joel Palefsky of the University of California, San Francisco described research showing that HPV-associated anal cancers and precancers are prevalent and on the rise in HIV-infected men who have sex with men and women. Although anal-cancer screening guidelines are not as definitive as those for cervical cancer, the disease seems to follow the same course, Palefsky said. His team is conducting a study to see if removing precancerous lesions prevents anal cancer in the same way it does for cervical cancer.
- Dr. Roshan Bastani of the University of California, Los Angeles led a phone-based intervention study to increase HPV vaccination. Bastani’s study was aimed at low-income, ethnic minority families in Los Angeles who had called a health hotline. Interestingly, her study found that both the control group who didn’t receive information about the vaccine and the group who did increased their child-vaccination rates. Bastani thinks that’s because the survey her team conducted to enroll people in the study was enough to give them the extra information they needed to get their children vaccinated. For her, this was good news: “In some populations where the [vaccination] rate is very low, you can get the low-hanging fruit with something that is very minimal,” she said. “So we need to all do that.”
Rachel Tompa is a former staff writer at Fred Hutchinson Cancer Research Center. She has a Ph.D. in molecular biology from the University of California, San Francisco and a certificate in science writing from the University of California, Santa Cruz. Follow her on Twitter @Rachel_Tompa.
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