Sara Pai, MD, PhD, a surgeon-scientist in the Department of Surgery at Massachusetts General Hospital, is the first author of a new study in the LANCET Health Longevity, Effects of Periodontitis on Cancer Outcomes in the Era of Immunotherapy. Fernando Guastaldi, DDS, MSc, PhD, a surgeon-scientist in the Department of Oral and Maxillofacial Surgery at Massachusetts General Hospital, is the senior author.

What Question Were You Investigating?

Given the economic impact of cancer care and periodontitis (gum disease) on the increasingly aging population, we explore the potential interplay of the oral microbiome and cancer immunotherapy.

Fernando Guastaldi, DDS, MSc, PhD

More specifically, we review the causes of periodontitis and its associated systemic complications and examine whether treating the oral microbial dysbiosis associated with periodontitis in patients with cancer could improve cancer outcomes and contribute to reducing racial cancer disparities in the era of immunotherapy.

What Approach Did You Use?

References for this review were identified through a search of PubMed for articles published between January 1, 1996, and January 29, 2023, with the keywords “periodontitis” AND “immune-related adverse event”, and no language restrictions. No results were found with these search words.

Sara Pai, MD, PhD

Subsequently, other searches using the keywords “periodontitis” AND “cancer immunotherapy response” OR “oral microbiota” AND “cancer immunotherapy response” were done.

Of 95 articles from this search, five relevant references were reviewed and included in the paper based on relevance to periodontal disease and cancer immunotherapy. We did not identify any publications that comprehensively reviewed this subject.

Due to the nature of this topic, the review is based on our multidisciplinary approach and clinical expertise pertaining to oral polymicrobial infections and cancer immunotherapy.

What Were the Results?

Periodontitis results from dysbiosis of the oral microbiome and affects up to 70% of US adults aged 65 years and older. Over 50 systemic inflammatory disorders and comorbidities are associated with periodontitis, many overlapping with immunotherapy-associated toxicities.

Despite the increasing use of immunotherapy for cancer treatment, uncertainty remains about whether the microbial shift associated with periodontal disease can influence response rates and tolerance to cancer immunotherapy.

We herein review the pathophysiology of periodontitis and the local and systemic inflammatory conditions related to oral dysbiosis and discuss the overlapping adverse profiles of periodontitis and immunotherapy.

The effects of the presence of Porphyromonas gingivalis, a key pathogen in periodontitis, highlight how the oral microbiome can affect the hosts’ systemic immune system, and further research into the local and systemic influence of other microorganisms causing periodontal disease is necessary.

What Are the Clinical Implications?

Several clinical questions regarding the potential effects of periodontitis on immune-related toxic impact and response to cancer immunotherapy remain and require further investigation.

Standard mechanical treatment of periodontitis can restore the periodontium to a healthy condition. However, the local treatment of periodontal disease can also re-equilibrate host immune health (both locally and systemically) by shifting the oral and gut microbiome to baseline health conditions.

Another unanswered question is whether targeting serum inflammatory markers, specific periodontal pathogens (e.g., P gingivalis), and associated key virulence factors improves response to immune checkpoint blockade (ICB) in patients with cancer.

Extrapolating from the current knowledge and literature, we provide a rationale for why patients with cancer should be evaluated and treated for periodontal disease before the initiation of immunotherapy.

These patients should also be included in short-term follow-up periods for supportive periodontal therapy to maintain dental health.

Because non-Hispanic Black, Hispanic, Native American, and Alaska Native people generally have the poorest oral health compared with other US racial and ethnic groups, we hypothesize that managing periodontitis could help to reduce cancer disparities by improving response rates and reducing ICB toxicity profiles in underrepresented minorities and individuals with a lower socioeconomic status.

Due to the high costs of these novel drugs, immune checkpoint inhibitors are more often used in high-income countries, and, accordingly, most of the literature on immunotherapy comes from these regions.

An unmet need to increase access to these drugs in low-income and middle-income countries persists and might allow a better understanding of response rates across a broader patient population with little access to periodontal care.

Paper Cited:

Pai, S. I., Matheus, H. R., & Guastaldi, F. P. S. (2023). Effects of periodontitis on cancer outcomes in the era of immunotherapy. The Lancet. Healthy longevity, 4(4), e166–e175.

About the Massachusetts General Hospital

Massachusetts General Hospital, founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The Mass General Research Institute conducts the largest hospital-based research program in the nation, with annual research operations of more than $1 billion, and comprises more than 9,500 researchers working across more than 30 institutes, centers, and departments. In July 2022, Mass General was named #8 in the U.S. News & World Report list of "America’s Best Hospitals." MGH is a founding member of the Mass General Brigham healthcare system.