This course was published in the January 2023 issue and expires January 2026. The authors have no commercial conflicts of interest to disclose. This 2 credit hour self-study activity is electronically mediated.
AGD Subject Code: 149
After reading this course, the participant should be able to:
- Discuss the prevalence and risks associated with cancer and periodontal disease.
- Identify the association between oral bacteria and colon, gastric and oropharyngeal cancers.
- List additional factors that impact oral health and cancer risk, and explain innovative methods that may help patients improve and maintain oral health.
Oral health is essential to overall health, and systemic diseases and their treatment often have significant oral manifestations. Conversely, oral infections may raise the risk of morbidities, including cancer.1 A correlation between periodontal disease and various cancers has been reported, and research is ongoing. For example, meta-analysis showed a statistically significant association between periodontal disease and all cancers, both combined and individually.2 The cancers studied included gastrointestinal, pancreatic, prostate, breast, corpus uteri, lung, hematological, esophageal/oropharyngeal and non-Hodgkin lymphoma.2 Through interprofessional collaboration, healthcare providers can play a vital role in the prevention and early treatment of oral and systemic diseases by identifying their initial signs and symptoms. In the dental setting, this approach should not only improve oral health, but also contribute to better medical outcomes and optimal overall health.
In the United States, cancer is the second leading cause of mortality, behind only cardiovascular disease.3 Cancer results in more than 10 million deaths per year across the globe.3 Considered as some of the deadliest diseases, cancers of the colon, gastrointestinal system and oropharynx often result in mortality.4–6
Due to the translocation of bacteria, many mutualistic oral microorganisms are associated with various cancers. In some cases, the initiation of the tumor process is not due to activities of a specific organism but, rather, instability in the composition of the bacterial communities, or dysbiosis. This is frequently associated with the increased inflammatory responses found in conditions such as periodontal disease.2
Six in 10 Americans have a chronic disease (Figure 1), and this number is only expected to increase.7 As such, oral health professionals should be knowledgeable about how the oral cavity is linked to systemic diseases and cancers. A 2019 survey found that two-thirds of patients with periodontitis were unaware of the correlation to systemic disease or the benefits of treating the systemic disease with periodontal therapy.8
Considered the most common chronic inflammatory condition, periodontitis is prevalent among those between the ages of 45 and 64, with one in 10 in this age group experiencing advanced disease.1,5 Although various periodontal pathogens play a significant role in the development of periodontal conditions, Fusobacterium nucleatum is a major contributor. This Gram-negative bacterium is critical in bacterial biofilm formation,5 and produces serine proteases that can destroy the extracellular matrix proteins, fibrinogen, fibronectin, and type I and IV collagen.5,9 The resultant inflammatory response causes alveolar bone destruction and loss of tissue attachment.10
Bacteria can be transmitted throughout the body through many routes, one of which is the swallowing of oral bacteria. Swallowed saliva and ingested food/fluids spread the microbiota of the oral cavity, providing a passage to the gastrointestinal tract. Another route of bacterial transmission is through the bloodstream and systemic circulation to the joints, heart and colon. Oral microbiota can directly access the bloodstream during toothbrushing, mastication or tooth extraction procedures. Gram-negative microorganisms — such as F. nucleatum, Porphyromonas gingivalis and other bacteria — are able to invade the bloodstream through ulcerated gingival pockets.4
Periodontal disease can significantly increase inflammatory markers and molecules that affect the inflammatory response, which, in turn promotes the release of reactive oxygen species and other metabolites that support cancer initiation.11 Studies show periodontal disease may be linked to colon and gastric cancer due to the abundance of similar bacteria in these areas.4,9 The presence of F. nucleatum produces interleukin-8, which increases local inflammation.10 Consequently, T-cell responses are suppressed and peripheral white blood cells die. Innate antimicrobial peptides and human B defensins within gingival epithelial cells increase, thereby suppressing the growth of other competitors.10 Periodontal disease is a risk factor for cancer due to the long-standing chronic inflammatory status of the periodontal tissues.11
Colon cancer is the third most common cancer in the United States and fourth leading cause of cancer-related death worldwide.4 The term colorectal cancer refers to a slowly developing cancer that begins as a tumor or tissue growth on the inner lining of the rectum or colon. If this abnormal growth, known as a colorectal polyp, becomes cancerous, it can form a tumor on the wall of the rectum or colon. Subsequently, the condition can spread to lymph nodes or blood vessels which, in turn, increases the chance of metastasis to other sites.9 Studies show that many bacterial members associated with the oral microbiota appear in gastrointestinal tumors, especially those associated with colorectal cancer.4 Research by Nakatsu et al12 found high numbers of oral bacteria — including Fusobacterium, Gemella, Peptostreptococcus and Parvimonas — within tumors in those diagnosed with colon cancer.
Gastric cancer is the fifth most common cancer worldwide. More than 1 million cases are diagnosed annually, and approximately 783,000 people will die as a result.5 The anatomical regions for gastric adenocarcinomas are classified as cardia or noncardia, also known as distal stomach cancer. Cardia gastric cancers are related to obesity or gastroesophageal reflux disease. Distal stomach cancers are the most common cause of chronic gastritis and inflammation of the gastric mucosa. Environmental factors, such as dietary habits and low socioeconomic status, increase stomach cancer risk. Frequently malignant, gastrointestinal tumors are associated with high morbidity and mortality, as well as low rates of early diagnosis.5
Gastric microbiota have a high number of bacterial translocation. Bacterial species associated with oral conditions, such as caries and periodontitis (including Fusobacteria, Porphyromonas, Prevotella, Klebsiella, Neisseria, Rothia, Veillonella and Streptococcus), are also linked with the gastric microbiome. High levels of F. nucleatum, Clostridium colicanis and Lactobacillus are contributing factors for gastric cancer.5
Each year, approximately 690,000 cases of cancers of the lip, oral cavity, pharynx or larynx are reported worldwide, making head and neck cancer the sixth most common cancer.6 Men are 3.5 times more likely to develop oropharyngeal cancer than women.1 Infection with the human papillomavirus (HPV) is associated with oropharyngeal cancer. A strong relationship also exists between periodontitis and oropharyngeal cancer among HPV-positive individuals. Research shows that chronic generalized periodontitis is predominant in approximately 80% of patients with oral and/or oropharyngeal cancer.13
Oral dysbiosis is a frequent event in oral and oropharyngeal carcinogenesis. Using an oral rinse as a platform for oral microbiome characterization, Lim et al14 found the oral microbiome was capable of noting oral cavity cancer and oropharyngeal cancers with 100% and 90% sensitivity and specificity, respectively. These findings concur with previous results that suggest differences in microbial abundance and diversity may play a role in cancer initiation and progression.
IMPACT OF THE HUMAN PAPILLOMAVIRUS
Additionally, HPV infections are contributing factors in both periodontal disease and oropharyngeal cancer. Lim et al14 found that implementing early intervention for periodontitis with scaling and root planing reduced the risk of pharyngeal cancer, particularly in patients with a history of periodontitis extending beyond three years.
A significant relationship exists between P. gingivalis, periodontitis, and head and neck cancers.15 Both the severity and extent of periodontitis may be considered potential risk indicators for oropharyngeal cancer, even after adjustments for tobacco and alcohol use.16 Furthermore, self-reported poor oral hygiene is an independent risk factor for high-risk HPV infections.17 Thus, receiving adequate oral care may reduce the risk of periodontitis and oropharyngeal cancers.
ADDITIONAL CONTRIBUTING FACTORS
Although progress has been made in advancing oral health, challenges remain in securing long-lasting behavioral changes. Healthy habits, such as regular dental visits, proper nutrition, and sufficient oral self-care, are key to maintaining optimal oral and systemic health.1
Unhealthy habits also impact oral and systemic health. Tobacco use harms oral tissues and is directly implicated in oral cancer, as well as periodontal disease. According to the U.S. Surgeon General, the prevalence of cigarette smoking continues to decline; however, the use of e-cigarettes and vaping products for both tobacco and marijuana is rising.1 This new threat to oral health warrants close attention to its ramifications for oral and other cancers.
Additional risk factors for oral and systemic disease are mental illnesses or substance use disorders that hinder individuals’ ability to adequately perform oral hygiene and seek regular dental care.1 Alcohol is also a contributing factor for colorectal, oropharyngeal and gastric cancers, as well as for periodontitis.5,9,16
Socioeconomic status, diabetes, age, gender, obesity, ethnicity, genetics and diet also impact periodontitis and cancer risk. Dietary factors are associated with advanced tooth loss and may be related to cancer risk.18 It has been estimated that for the 13 most common cancers in the United States, 31% of cases could be prevented through a healthy diet, physical activity, and maintaining a healthy weight.19
INNOVATIVE METHODS TO SUPPORT ORAL HEALTH
Myriad strategies are available to help patients improve oral health. The use of prebiotics and probiotics is emerging as a supportive oral health measure.20 The role of probiotics in manipulating oral microbiota as a strategy to prevent oral disease has shown interesting potential. Enhancing the use of probiotic microorganisms as biotherapeutic agents may be a promising approach to achieving optimal oral health; however, more research is necessary.21
Host modulation therapy, which is intended to control and reduce local inflammation, may be helpful in supporting oral health and reducing systemic inflammation.21 Antimicrobial peptides can affect the homeostasis of the oral cavity by selectively killing bacteria, but can also modulate both innate and adaptive immune responses through their immunomodulatory properties.20 Recent research shows that some antimicrobial peptide levels in saliva, such as LL-37, human neutrophil peptide 1–3, substance P, adrenomedullin and azurocidin, are elevated in individuals with periodontal disease.20 Therefore, monitoring these levels could be used either as a disease marker or means of targeting specific oral bacteria.
Nutrition is integral to oral and systemic health. A mini-review determined that periodontal disease is associated with deficiencies of vitamins A, B, C, D and E, as well as folic acid, calcium, zinc and polyphenols.22 Moreover, the antioxidant effects of vitamins and intake of anti-inflammatory drugs can positively impact the prevention and treatment of periodontal disease and cancers; in the latter case, not only by preventing the growth of new polyps, but also stunting the growth of existing polyps.5,9
Analysis of salivary biomarkers offers potential for the accurate diagnosis of both oral and systemic diseases.20 Several kits are available for chairside use to detect caries, periodontal disease and IL-6 polymorphism. A tool to help clinicians assess the risk of oral squamous cell carcinoma is also on the market. In addition, techniques such as liquid biopsies and salivary liquid biopsies are currently under investigation and may offer promising potential in cancer diagnosis.20
Oral health is key to maintaining overall health. As part of a multidisciplinary care team, dental professionals can help patients realize optimal oral and systemic health through preventive treatment and early diagnosis and intervention. While many contributing factors affect oral and systemic diseases and their progression, the risk for periodontal disease and cancer may be mitigated through education, proper diet, regular dental treatment, and an effective self-care regimen.1,18
Bacterial pathogens alone are unable to induce cancer; rather, an overly aggressive immune response to chronic inflammation can result in mutations in oncogenic signaling pathways, leading to cancer pathogenesis. The implementation of new clinical approaches — along with improved diagnostics offered by salivary biomarkers and other advanced techniques — have the potential to facilitate prevention and management of periodontal disease and cancer alike. Many microorganisms in the oral cavity are also found in the colorectal and gastrointestinal tracts, as well as the oropharynx. As a result, collaborating with other healthcare providers to educate patients about the oral-systemic link and benefits of maintaining optimal oral health can help prevent many oral and systemic diseases — including cancer.
- National Institutes of Health. Oral Health in America: Advances and Challenges: Executive Summary. Available at: https://www.nidcr.nih.gov/sites/default/files/떕-12/Oral-Health-in-America-Executive-Summary.pdf. Accessed November 29, 2022.
- Irfan M, Delgado R, Frias-Lopez J. The oral microbiome and cancer. Front Immunol. 2020;11:591088.
- Morgan KK. How many people die of cancer a year? Available at: https//www.webmd.com/cancer/how-many-cancer-deaths-per-year. Accessed November 29, 2022.
- Koliarakis I, Messaritakis I, Nikolouzakis TK, Hamilos G, Souglakos J, Tsiaoussis J. Oral bacteria and intestinal dysbiosis in colorectal cancer. Int J Mol Sci. 2019;20:4146.
- Șurlin P, Nicolae FM, Șurlin VM, et al. Could periodontal disease through periopathogen Fusobacterium nucleatum be an aggravating factor for gastric cancer? J Clin Med. 2020;9:3885.
- Farran M, Løes SS, Vintermyr OK, Lybak S, Aarstad HJ. Periodontal status at diagnosis predicts non-disease-specific survival in a geographically defined cohort of patients with oropharynx squamous cell carcinoma. Acta Oto-Laryngologica. 2019;139:309–315.
- U.S. Centers for Disease Control and Prevention. Chronic Diseases in America. Available at: https://www.cdc.gov/chronicdisease/resources/infographic/chronic-diseases.htm. Accessed November 29, 2022.
- Nazir M, Izhar F, Akhtar K, Almas K. Dentists’ awareness about the link between oral and systemic health. J Family Community Med. 2019;26:206–212.
- Marley AR, Nan H. Epidemiology of colorectal cancer. Int J Mol Epidemiol Genet. 2016;7:105–114.
- Lee D, Jung KU, Kim HO, Kim H, Chun HK. Association between oral health and colorectal adenoma in a screening population. Medicine (Baltimore). 2018;97:e12244.
- Corbella S, Veronesi P, Galimberti V, Weinstein R, Del Fabbro M, Francetti L. Is periodontitis a risk indicator for cancer? A meta-analysis. PLoS ONE. 2018;13:1–15.
- Nakatsu G, Li X, Zhou H, Sheng J, Wong SH. Gut mucosal microbiome across stages of colorectal carcinogenesis. Nat Commun. 2015;6:8727.
- Ortiz AP, González D, Vivaldi-Oliver J, et al. Periodontitis and oral human papillomavirus infection among Hispanic adults. Papillomavirus Res. 2018;5:128–133.
- Lim Y, Fukuma N, Totsika M, Kenny L, Morrison M, Punyadeera C. The performance of an oral microbiome biomarker panel in predicting oral cavity and oropharyngeal cancers. Front Cell Infect Microbiol. 2018;8:267.
- Chen PJ, Chen YY, Lin CW et al. Effect of periodontitis and scaling and root planing on risk of pharyngeal cancer: a nested case-control study. Int J Environ Res Public Health. 2020;18:8.
- Moraes RC, Dias FL, Figueredo CM, Fischer RG. Association between chronic periodontitis and oral/oropharyngeal cancer. Braz Dent J. 2016;27:261–266.
- Sun CX, Bennett N, Tran P, et al. A pilot study into the association between oral health status and human papillomavirus-16 infection. Diagnostics (Basel). 2017;7:11.
- Seneviratne CJ, Balan P, Suriyanarayanan T, et al. Oral microbiome-systemic link studies: perspectives on current limitations and future artificial intelligence-based approaches. Crit Rev Microbiol. 2020;46:288–299.
- Theodoratou E, Timofeeva M, Li X, Meng X, Ioannidis J. Nature, nurture, and cancer risks: genetic and nutritional contributions to cancer. Annu Rev Nutr. 2017;37:293–320.
- Thomas C, Minty M, Vinel A, et al. Oral microbiota: a major player in the diagnosis of systemic diseases. Diagnostics (Basel). 2021;11:1376.
- Mahasneh SA, Mahasneh AM. Probiotics: a promising role in dental health. Dent J (Basel). 2017;5:26.
- Martinon P, Fraticelli L, Giboreau A, Dussart C, Bourgeois D, Carrouel F. Nutrition as a key modifiable factor for periodontitis and main chronic diseases. J Clin Med. 2021;10:197.
From Decisions in Dentistry. January 2023;9(1)30-33.