: start Clinical Context

Periodontitis has been associated with a higher risk for cardiovascular disease among adults, and a joint working group from the European Federation of Periodontology and American Academy of Periodontology addressed this issue in a statement published in the April 2013 issue of the Journal of Periodontology.[1]

The group found clear evidence from multiple studies that periodontitis was associated with an increased risk for cardiovascular disease that went beyond that associated with more traditional cardiovascular risk factors. This relationship was evident among women and men and in different age groups.

There were far fewer data on how the treatment of periodontitis might influence the risk for cardiovascular events. The group found moderate evidence that the treatment of periodontitis improved markers of systemic inflammation as well as measures of endothelial function. However, they found no studies that assessed periodontal treatment in the primary prevention of cardiovascular events, and there was only 1 low-quality study of treatment of periodontitis for secondary prevention.

The systemic inflammation associated with periodontitis may also represent a risk factor for cancer. The current study addresses this issue.

Study Synopsis and Perspective

Severe gum disease may increase not only the risk for cancer, including lung and colorectal cancer, but also the likelihood of dying of the disease, particularly pancreatic cancer, suggest results from 2 large-scale studies from the United States and Finland.

The US study, led by Dominique Michaud, ScD, professor of public health and community medicine at Tufts University School of Medicine, Boston, Massachusetts, included almost 7500 individuals who had undergone dental examination. Of them, more than 1600 developed cancer.

The findings, which were published online in the Journal of the National Cancer Institute on January 12, showed that severe periodontitis was associated with a 24% increased risk for cancer, with the highest risks seen for lung cancer and colorectal cancer.[2]

“This is the largest study addressing the association of gum disease and cancer risk using dental examinations to measure gum disease prior to cancer diagnosis,” Dr Michaud said in a statement.

“Additional research is needed to evaluate if periodontal disease prevention and treatment could help alleviate the incidence of cancer and reduce the number of deaths due to certain types of cancer,” he added.

Although also acknowledging the need for more work on, for example, the racial disparities they identified in the study, the team believe that their findings underline the need for expanded access to dental insurance.

Study coauthor Elizabeth Platz, ScD, from Johns Hopkins Bloomberg School of Public Health and the Johns Hopkins Kimmel Cancer Center, Baltimore, Maryland, said, “Knowing more about the risks that come about with periodontal disease might give more support to having dental insurance in the way that we should be offering health insurance to everyone.”

In the second study, lead author Timo Sorsa, DDs, PhD, from the University of Helsinki and Helsinki University Central Hospital, Finland, and colleagues examined registry data on more than 68,000 adults who had made a primary dental healthcare visit.[3]

This revealed that periodontitis was associated with a 33% increased risk for overall cancer mortality. The mortality risk associated with gum disease among individuals with pancreatic cancer was far higher, with a more than 2-fold increased risk.

The study was published in the International Journal of Cancer on January 11.

Dr Sorsa and colleagues also refer to another study they conducted, recently published in the British Journal of Cancer, which shows that a virulence factor associated with a bacterium seen in periodontitis also occurs in gastrointestinal tumors.[4]

“These studies have demonstrated for the first time that the virulence factors of the central pathogenic bacteria underlying gum disease are able to spread from the mouth to other parts of the body, most likely in conjunction with the bacteria, and take part in central mechanisms of tissue destruction related to cancer,” Dr Sorsa said in a statement.

As a consequence, the prevention and early diagnosis of periodontitis could be important for not only oral health but also overall well-being.

“In the long run, this would be extremely cost-effective for society,” said Dr Sorsa.

Largest Study Based on Dental Exam 

To date, most studies looking at the association between periodontitis and cancer risk have relied on self-reports. In contrast, the study conducted by Dr Michaud and colleagues included a dental examination.

The team used data from the Atherosclerosis Risk in Communities study cohort, a prospective analysis of 15,792 individuals aged 44 to 66 years who were recruited from 4 areas of the United States between 1987 and 1989.

All the participants took part in a baseline examination, followed by 3 follow-up visits over the course of 10 years. At the fourth visit, the remaining participants were invited to undergo a clinical dental examination that probed depth and gingival recession at 6 sites.

Via linkage to state cancer registries, supplemented by medical records and hospital discharge codes, the team assessed the cancer incidence between 1987 and 2012; cancer deaths were obtained from death certificates.

Ruling out participants with a cancer history, the team included in the current analysis 6056 individuals who underwent the dental examination and 1410 who had no teeth (ie, were edentulous).

Depending on the definition used, 2420 to 2543 individuals had no or mild periodontitis, whereas 2104 to 2514 had moderate periodontitis and 1122 to 1409 had severe periodontitis.

More severe periodontitis, regardless of the definition of severity used, was associated with being older, male, black, less educated, obese, and a smoker.

During a mean follow-up of 14.7 years, there were 1648 incident cancers and 547 cancer deaths in the study population.

Compared with individuals who had no or mild periodontitis, those who had severe periodontitis (defined as >30% of sites with attachment loss >3 mm) had a significantly increased risk for total cancer, at a hazard ratio of 1.24 (P = .004).

A similar association was observed between edentulism and total cancer risk; the hazard ratio compared with no or mild periodontitis was 1.28.

The association between severe periodontitis and cancer risk was particularly strong for lung cancer, at a hazard ratio of 2.33 (P<.001) vs no or mild periodontitis, even after taking into account cigarette smoking status and pack-years of smoking.

However, the association was present only in white individuals and was stronger in men than women.

When the team looked at colorectal cancer, they found that edentulism was associated with a significant 80% increased risk, whereas severe periodontitis was associated with a 50% increased risk. Among never-smokers, the risk for colorectal cancer was increased more than 2-fold and was present in both white and black participants.

There was a significant increased risk for pancreatic cancer among participants with severe periodontitis. No association was seen for breast, prostate, or hematopoietic and lymphatic cancers.

Link to Pancreatic Cancer 

In the Finnish study, Dr Sorsa and colleagues used the patient register from Helsinki’s Public Dental Service to identify individuals aged 29 years or older who had made at least 1 primary dental healthcare visit in 2001 or 2002.

These were linked to the register of deaths from Statistics Finland, which provided information on both the date and case of death. In addition, socioeconomic and education data were obtained, and drug prescriptions were collated alongside cancer diagnosis data from the Finnish Cancer Registry.

The researchers included 68,273 patients, yielding 664,020 person-years during a median follow-up of 10.1 years. The mean age at baseline was 43 years, and 58% of patients were women.

The most common dental procedure was endodontic treatment, in 70.3% of patients, followed by treatment for gingivitis in 40.6% of patients and periodontitis treatment in 20.5%.

During follow-up, there were 797 cancer deaths, of which 199 (25%) were in patients with periodontitis, for a crude cancer mortality rate of 14.45 per 10,000 person-years.

In comparison, the crude cancer mortality rate among individuals without periodontitis was 11.36 per 10,000 person-years.

The most common diagnosis in patients who died of cancer was lung cancer, at a crude mortality rate of 2.42 per 10,000 person-years, followed by breast cancer (1.89 per 10,000 person-years), pancreatic cancer (1.13 per 10,000 person-years), and prostate cancer (0.95 per 10,000 person-years).

Further analysis showed that after adjustment, periodontitis was associated with a significantly increased risk for both overall and pancreatic cancer mortality, at mortality rate ratios of 1.33 and 2.32, respectively.

Michaud and colleagues’ study was supported by awards from the National Cancer Institute of the National Institutes of Health. The Atherosclerosis Risk in Communities study was supported by awards from the National Heart, Lung, and Blood Institute of the National Institutes of Health. Sorsa and colleagues’ study was supported by grants from the Finnish Women Dental Society and the Helsinki University Tulevaisuusrahasto, the Helsinki University Hospital Research Foundation, Helsinki, Finland, and the Karolinska Institutet, Stockholm, Sweden. No authors have disclosed any relevant financial relationships.

J Natl Cancer Inst. Published online January 12, 2018.

Int J Cancer. Published online January 11, 2018.

Study Highlights

  • Researchers used the Atherosclerosis Risk in Communities study to evaluate their hypothesis. The study enrolled 15,792 adults between the ages of 44 and 66 years from 4 distinct regions in the United States between 1987 and 1989.
  • The fourth study visit between 1996 and 1998 included a dental exam. Periodontitis was measured using 2 different standards, and edentulous status was determined by participant self-report.
  • The main study outcome was incident cancer from 1987 to 2012. Cancer cases were ascertained from state cancer registries.
  • The study results were adjusted to account for known cancer risk factors.
  • 7466 adults had either periodontitis or were edentulous. Most participants were women, and the median age of participants was in the early sixth decade.
  • Variables associated with more severe periodontitis included older age, male sex, black race, obesity, lower educational attainment, and smoking.
  • Compared with participants with no or mild periodontitis, those with severe periodontitis experienced a hazard ratio of 1.24 (95% confidence interval, 1.07-1.44) for cancer. A similar hazard ratio was noted for edentulism (hazard ratio, 1.28; 95% confidence interval, 1.09-1.50).
  • The association between periodontitis and the risk for cancer was significant among white adults, but not black adults. The risk for periodontitis was also significant among men, but not women.
  • Edentulism and periodontitis were both significantly associated with a higher risk for cancer death during the follow-up period. Again, this result was only significant for white adults.
  • A subgroup analysis focused on never smokers and found that the association between periodontitis and cancer was attenuated in this group.
  • Adjusting the results to account for participants’ socioeconomic status did not substantially alter the main study conclusions.
  • The cancer types most closely associated with periodontitis included lung and colorectal cancer. Other orodigestive cancers were also more common in cases of periodontitis.
  • Periodontitis was not related to the risk for breast and prostate cancer, or hematopoietic and lymphatic cancer.

Clinical Implications

  • A previous review found good evidence that periodontitis is associated with an increased risk for cardiovascular disease. This relationship was evident among women and men and in different age groups. The group also found moderate evidence that the treatment of periodontitis improved markers of systemic inflammation as well as measures of endothelial function. However, they found no studies that assessed periodontal treatment in the primary prevention of cardiovascular events.
  • Periodontitis and edentulism were significant associated with higher risks for cancer in the current study, especially lung and colorectal cancer. The association between periodontitis and the risk for cancer was significant among white adults, but not black adults.
  • Implications for the Healthcare Team: In treating the whole patient, the healthcare team should emphasize oral healthcare. Routine follow up for oral healthcare should be part of the health maintenance agenda.