This blog post is Part I in a two-part series on the microbiome and cancer. See here for Part II.

Some of the earliest-observed links between the human microbiome and cancer were the distinct patterns found in the microbiomes of healthy individuals compared to those with various carcinomas. Study after study showed that people with colorectal cancer, for example, have different gut microbiome compositions from healthy people; and furthermore, the functions of these microbiomes appear altered in a consistent way across different populations and geographies.

Dr. Christine Pierce, Assistant Member at Moffitt Cancer Center, is an epidemiologist and researcher who approaches questions about cancer pathogenesis from a ‘molecular epidemiology’ perspective. Early in her career, Dr. Pierce began studying the development of head and neck cancer—specifically, human papillomavirus (HPV)-driven head and neck cancer. And as next-generation gene sequencing technology became more and more accessible to research groups, she and a colleague began to wonder whether aspects of the microbiome contributed to the etiology of these cancers.

Below is part one of our Q&A with Dr. Pierce.

What is molecular epidemiology, and what does it have to do with etiology of cancer?

Epidemiology as a whole is the study of diseases in populations, and ways in which we can consider different risk factors for disease, or risk factors for the progression of a disease if we’re talking about cancer specifically.

Molecular epidemiology is a branch of epidemiology that focuses on molecular risk factors: say, genetic or environmental risk factors that may contribute to the cause and prevention of disease across populations.

My work within head and neck cancer and the human papillomavirus, has to do with thinking about various environmental (because I consider microbes environmental) risk factors—things that you can pick up in the environment, in addition to traditional risk factors like cigarette smoking.

So in a lot of epidemiological studies we will capture pieces of information from, say, questionnaires. Going back to cigarette smoking, you would ask someone about their smoking history. That’s very traditional epidemiology, using those questionnaires.

Molecular epidemiology will use different biomarkers that are collected with biological specimens. For example, measuring something in the blood; measuring something in the stool when it comes to thinking about microbiome. They’re actually biospecimen-based markers that allow us to more objectively measure certain aspects of health, or certain research-oriented items that we would want to be able to consider as a risk factor. Or something that may modify the disease process.

It’s really focused on the molecular side, meaning a more objective measurement using a laboratory, as opposed to someone’s recall based on a questionnaire question that may or may not be subjective.

You worked on a virally caused cancer. What made you think of the microbiome as a contributing factor in how the cancer develops and progresses?

I did a lot of work during my postdoc on a subset of cancers, and during my time working with that I started to think about ways in which other microbial factors may be influencing the viral persistence that happens in the oral cavity, or the mouth, of people who do go on to develop these types of head and neck cancers.

It was through my research on viruses and cancer that I started to think about the role of bacteria or fungi and the virus that leads to cancer. That really started my interest in the field, trying to help me understand what factors within the oral cavity may be contributing to the persistence of this particular virus.

How could microbial communities play a role in the development of various cancers?

Researchers in head and neck cancers have realized that poor oral hygiene has been a risk factor for head and neck cancer—numbers of teeth lost, cigarette smoking, a variety of things that contribute to poor oral health have been reported to increase risk for head and neck cancer. So thinking about not just one particular type of bacteria that may be present in the mouth, but about the communities of bacteria that may be increasing inflammation or that may be contributing to increased infection or increased immune markers—both inflammatory and immune markers locally that may be setting the stage for a more persistent viral infection, at least within the context of these HPV-driven cancers. So definitely thinking about the community of bacteria as a whole, as opposed to an individual bacterium that may be contributing to cancer.

There’s a difference between infections that are known to cause cancers, that are driven solely by themselves. HPV would be one—it’s a virus that’s known to have oncogenic properties and can actually cause cancer… it doesn’t need the help of other viruses around it or other bacteria around it. Same thing with Helicobacter pylori as a bacterium that can cause stomach cancer. Those are examples of microorganisms that can independently cause cancer themselves.

But really, the role of the microbiome is thinking about communities of microbes, whether it be multiple bacteria, multiple fungi, multiple viruses, and/or groups of bacteria and fungi and viruses together. [It involves] thinking about those communities as a whole and how they may be contributing to immune responses and inflammation in the local environment, or even thinking about ways in which it can impact the entire body, which is really the systemic effects of those microbes.

Outside the colon, the mouth is the second most microbe-filled environment in your body. And thinking about the role that those microbes may be playing locally, and how that may impact the development of cancer in the mouth, makes a lot of sense if you start thinking about local effects of things.

Currently, how much of your research focuses on cancer etiology?

I do have some work that’s in pathogenesis but it’s harder at a cancer center to study etiology, because the access we have is to patients with cancer. Here, it’s a lot easier to do research on therapeutic outcomes than to do traditional epidemiology, which is really focused on etiology. You’d need a lot of healthy individuals and interesting different study designs to be able to do that. So my research largely now focuses on the therapeutic outcomes.

This interview has been edited for clarity and length.