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Science in the News

Prospective Cohort Study on Periodontal Disease as Cancer Risk Factor

August 11, 2017

A prospective cohort study evaluated periodontal disease as a risk factor for incident cancer.1 Participants were 65,869 postmenopausal women who had completed a survey on periodontal disease as part of the Women’s Health Initiative Observational Study, an ongoing cohort designed to investigate factors affecting morbidity and mortality in older women.2 At enrollment, information on risk factors for cancer such as family history of cancer, tobacco exposure, diet, and age was collected via self-reported questionnaire. Five years later, participants were surveyed on whether a dentist or dental hygienist had ever told them they had periodontal or gum disease. From that time point until September 2013, any cases of invasive cancer (excluding nonmelanoma skin cancers) were considered incident cancer.

In total, 7,149 cancers were diagnosed in 65,869 women during a mean follow-up of 8.32 years (maximum follow-up was 15 years). The mean age of analyzed participants was 68.3 years, most were non-Hispanic Whites, had at least some college education, and reported visiting the dentist at least 2 times a year. Those who reported periodontal disease were more likely to report a history of smoking, secondhand smoke exposure, alcohol consumption, and menopausal hormone therapy (i.e., estrogen and progestin).  Those with or without recognized periodontal disease had similar rates of family history of any cancer, but those who reported periodontal disease also reported a significantly higher rate of any cancer diagnosis (13.3% compared to 11.1%). Self-reported periodontal disease was associated with a statistically significant 14% (hazard ratio: 1.14, 95% confidence interval: 1.08-1.20) increased risk in total cancer, after adjusting for age, years smoked, and body mass index. In terms of specific cancers, women with periodontal disease had significantly higher risks of cancer in the lung and bronchus, respiratory or intrathoracic organs, upper gastrointestinal tract, and breast. Periodontal disease history was not significantly associated with cancer in other locations, including the lip, oral cavity, or pharynx.

The study authors suggest that the lack of association with lip, oral, and pharynx cancers may be due to the small number of incident cases and heterogeneity between these anatomic sites. The mechanisms by which periodontal disease may promote cancer in other, more distant organs remain unclear. It has been posited that oral pathogens that escape into systemic circulation may persist long enough to activate toll-like receptors, activation of which has been linked to cellular proliferation, invasion, and evasion of antitumoral immune responses. Toll-like receptor activation has also been linked to inflammation, which may cause oxidative/nitrosative stress that could induce DNA mutations or interfere with DNA repair mechanisms. 

There are limitations to this study. With the large number of statistical tests conducted, and no control for the familywise error rate, the study has a high probability of finding a significant result by chance. Periodontal disease in this study was based on self-report, which is prone to misclassification. The likelihood that a woman in the periodontal disease group did not have periodontal disease was 67.2%; the likelihood that a woman in the non-periodontal disease group actually had periodontal disease was 9.3%. The groups with and without self-reported periodontal disease are significantly different with regards to a number of factors that affect both periodontal disease and cancer, including age, race, smoking exposure, diet, and alcohol consumption. The study controls for some of these factors in the multivariate analysis, but not all of them, so the reported estimates may be confounded. This study also has a number of strengths. It is the first study of periodontal disease association with cancer among older women.2  Cancer cases were adjudicated by trained physicians, minimizing the chances of outcome misclassification. The cohort is large, which enables assessment of cancers of specific anatomical sites. The participants were followed for a long period of time, and important risk factors were evaluated from the outset, making it clear that risk factors preceded cancer incidence.

This study provides evidence that women diagnosed with periodontal disease are more likely to later be diagnosed with cancer. This supports a need for further research in the field, most especially whether treating periodontal disease can reduce cancer risk.


  1. Nwizu NN, Marshall JR, Moysich K, Genco RJ, Hovey KM, Mai X, et al. Periodontal disease and incident cancer risk among postmenopausal women: Results from the Women’s Health Initiative Observational Cohort. Cancer Epidemiology, Biomarkers & Prevention 2017;26(8):1255-1265.
  2. National Institutes of Health. Women’s Health Initiative Observational Study. Accessed 8/11/17.

Prepared by: Center for Scientific Information, ADA Science Institute

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