New York University (NYU) researchers compared the oral bacteria of participants in two large prospective cancer studies who subsequently developed head and neck squamous cell cancer with those who remained cancer-free. They wanted to determine if smoking tobacco, drinking alcohol, or the presence of human papillomavirus (HPV) affected the findings.
They found that a greater abundance of certain oral bacteria was indeed associated with a decreased risk of these cancers.
"These results are consistent with a role of the healthy oral microbiome in head and neck squamous cell cancer prevention," wrote the authors, led by Richard B. Hayes, DDS, PhD, MPH, a professor in the departments of population health and environmental medicine at the NYU School of Medicine (JAMA Oncology, January 11, 2018).
More than 550,000 new cases of head and neck cancer, which includes cancers of the oral cavity, pharynx, and larynx, are diagnosed worldwide each year, according to previous research. About 85% of these cases are head and neck squamous cell cancer, which may lead to physical disfigurement and a reduced quality of life for patients, and these patients have a five-year mortality rate of around 40%, the authors wrote. They emphasized the need for new approaches for preventing head and neck squamous cell cancer, in addition to existing efforts for controlling smoking, alcohol, and HPV.
“These results are consistent with a role of the healthy oral microbiome in head and neck squamous cell cancer prevention.”
— Richard B. Hayes, DDS, PhD, MPH, and colleagues
Studies have found that certain oral bacterial profiles are associated with head and neck cancer, but these investigations have been limited to oral cavity cancers and have not been able to determine if these bacteria were present before cancer development.
To learn more, the NYU researchers analyzed the oral microbiomes from mouthwash samples provided by healthy, cancer-free participants in prospective cancer studies to determine if their bacterial composition was related to their later cancer status.
They included data from 129 people diagnosed with head and neck squamous cell cancer during follow-up for the following two studies: 58 from the American Cancer Society's Cancer Prevention Study II (CPS-II) Nutrition Survey cohort and 71 from the National Cancer Institute's Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. For each patient case, the team also included two controls from the same study who did not develop cancer and were matched based on age, sex, race/ethnicity, and time since mouthwash sample collection, for a total of 254 control patients.
The American Cancer Society cohort included more than 184,000 U.S. individuals who ranged in age from 50 to 74 when they completed a baseline diet and lifestyle questionnaire in 1992. Since 1997, researchers mailed participants follow-up questionnaires every two years that included questions about diagnosis with cancer. They collected oral wash samples by mail from 70,004 of them in 2001 and 2002.
The PLCO was a randomized trial that studied the effects of screening on cancer-related mortality in individuals ages 55 to 74 at baseline in 1993 through 2001. The 52,000 participants who were randomly assigned to the study's control arm provided oral wash samples. During follow-up, they answered questions on incident cancers via an annual, mailed questionnaire.
The 129 incident cases drawn from these studies were diagnosed after a mean of 3.9 years of follow-up and histologically confirmed. They included cancers of the oral cavity (excluding salivary glands), pharynx (excluding nasopharynx), and larynx. The researchers analyzed bacterial genomic DNA from thawed mouthwash samples of patient cases and controls.
They found that a decreased risk of head and neck squamous cell cancer was associated with a greater abundance of the commensal bacterial genera Corynebacterium and Kingella. These findings were consistent in both cohorts and unrelated to the timing of microbiome sampling, indicating the presence of risk before disease occurrence, they reported. The findings were strongest in participants with a history of tobacco use and those with larynx cancer.
The investigators also found that patients diagnosed with head and neck squamous cell cancer were more likely than control patients to be current tobacco smokers, consume a larger amount of alcohol if they drank at all, and be positive for the oral presence of HPV-16.
"Our findings of stronger inverse association of these oral taxa with head and neck squamous cell cancer in current and former smokers suggest that the preventive effect of those taxa may be more pronounced in the high-carcinogen oral environment in smokers," the authors wrote.
However, they did not find that any bacteria known to be associated with periodontal disease and dental caries were associated with head and neck squamous cell cancer risk, even though previous studies have found periodontal disease, tooth loss, and infrequent tooth brushing to be linked to an increased risk. Previous research has found that periodontitis and caries are caused by mixed-species communities, they noted.
"Commensal bacteria associated with reduced risk for head and neck squamous cell cancer in our study may characterize a healthy oral microbiome that prevents disease development," they wrote.
Single sample limitation
The authors noted some limitations of their research:
- The study was observational and does not establish causality.
- Only a single oral sample from one site was available, while sampling at multiple time points and from other oral sites (such as tongue and dental plaque) would have been valuable.
- Most study participants were white.
However, the authors affirmed the value of the study's prospective design in testing the hypothesis that oral bacteria may be involved in the development of head and neck squamous cell cancer.
"The study provides the first comprehensive evidence that the oral microbiome may be associated with subsequent risk of head and neck squamous cell cancer, with the strongest links for larynx cancer and those with a history of tobacco use," they concluded.
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