Symbiosis is a term we learn in high school biology. It refers to a close, mutually beneficial living arrangement between two different species. Thus, we learn that we have a critically important symbiotic relationship with the microbiome, the huge collection of all microorganisms, including bacteria, viruses and fungi, that naturally inhabit our bodies both inside and outside of us.
There are at least 1,000 different types of bacteria included in this definition. In fact, it is estimated that there are 30 trillion bacteria living on or in each human being. They assist with normal digestion, control of the immune system, and with protection against harmful bacteria. From a cancer point of view, much attention has been focused on how the gut microbiome may affect the risk of cancers of the lower GI tract (colon, rectum, anus). But for today, we draw our attention to the oral microbiome and limit ourselves to bacteria.
Suggestions of a link between periodontitis (gum disease, especially infections) and leukemia go back as far as the early 1950s. Since then, many studies have been done that suggest a link between periodontal disease and various cancers. Meta-analyses show that non-smokers with periodontal disease have elevated risks of developing hematologic cancers and lymphoma; the relative risks were in the 1.2-1.3 range. A meta-analysis of eight studies published in 2017 in the Annals of Oncology found an elevated risk of pancreatic cancer for periodontitis (relative risk 1.74, 95% confidence interval 1.41-2.15) and for edentulism (absent teeth) of 1.54 (95% confidence interval 1.16-2.05). These studies also found an association with worse survival from pancreatic cancer. Several specific bacterial species were identified as being the culprits in these links.
Various oral microorganisms have been associated with cancers of the esophagus, pancreas, colorectum, stomach and breast. Not surprisingly, periodontitis has also been linked to squamous cell malignancies of the oropharynx. The hypothesis is that inflammation caused by these microorganisms increases the risk of this cancer. This increased risk is present even after controlling for other known risk factors of oropharyngeal cancer, such as tobacco and alcohol.
An individual’s oral microbiome may be affected by a number of external factors. These include cigarette smoking, high sugar intake, and the use of antimicrobials. Various infections in the oral cavity are common, such as gingivitis, periodontitis and dental caries, and can alter the oral microbiome as well. An individual typically ingests and swallows between 100 billion and one trillion micro-organisms, which then gain access to the gastrointestinal tract and may thereby affect the risk of cancers in that system as well as at other sites.
The microbe Porphyromonas gingivalis is particularly associated with oral squamous cell carcinoma. Carriage of this microorganism has been found to increase the risk of oral cancer by a relative risk of 1.36 (95% confidence interval 0.47-3.97). Other studies have found elevated levels of this particular microorganism in tissue samples from patients with oral cancer as compared to healthy controls.
Another bacterium found in association with oral cancer is Fusobacterium nucleatum. It is interesting that the concentration of this microorganism increases as the individual’s cancer stage increases from stage I to stage IV.
Multiple other microorganisms have also been identified as increased in the setting of oral cancer, and there are various viruses, such as human papillomavirus, also involved in oral carcinogenesis. Not surprisingly, many of the same microorganism species have also been found to be increased in conjunction with esophageal cancers.
Many of the microorganisms associated with one type or another of cancer are also associated with halitosis (bad breath). The same mechanisms may lead to the production of aldehydes, which lead to the odors. These microorganisms may also induce carcinogenesis through pro-inflammatory mechanisms. A third possibility is that they suppress localized immune protective mechanisms and thereby allow carcinogenic processes to proceed unimpaired.
This field is relatively early in its development. It is likely that new markers for the early detection of cancer may arise from the ongoing research in this area. I have not found studies that discuss strategies for the prevention of cancer through interventions focused on the oral microbiome, but I think it would not be a large leap to assume that cancer prevention would be yet one more good reason to maintain good dental care and prevention.
My sister-in-law used to say that as one ages, two major issues, among others, are the problems that arise with one’s teeth and with one’s gait—my experience has been that this was a very wise thought.
Alfred I. Neugut, MD, PhD, is a medical oncologist and cancer epidemiologist at Columbia University Irving Medical Center/New York Presbyterian and Mailman School of Public Health in New York. Email: [email protected].
This article is for educational purposes only and is not intended to be a substitute for professional medical advice, diagnosis, or treatment, and does not constitute medical or other professional advice. Always seek the advice of your qualified health provider with any questions you may have regarding a medical condition or treatment.
