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The demand for dentists who are trained to meet the oral healthcare needs of patients battling cancer and cancer survivors is rising. There were 11.9 million people living with cancer in the United States in 2008, the latest year for published statistics.1 Today, that number has risen to an estimated 14 million, and is expected to continue to rise to over 18 million by 2020.1 This increase in the number of individuals living with cancer is influenced by two factors: a rise in incidence and an increase in survival. The aging of the Baby Boomer generation has brought with it an increase in the number of new cancer cases reported each year. Today in the United States, the chance that a man will be diagnosed with cancer at some point during his lifetime is 1 in 2. Those odds for a woman are 1 in 3.1 At the same time, advances in modern treatments have increased the survival rate for many patients with cancer.2 New drugs, techniques, and protocols have led to a deeper understanding of the disease process and more effective treatment strategies. The end result is an ever-increasing population that requires a dentist who appreciates the uniqueness of dental and oral healthcare needs of patients with cancer and knows how to render appropriate care.
Over the past few years, there has been a shift in where cancer treatment is given in the United States. More and more patients are able to receive quality cancer care closer to home rather than needing to travel to a large national cancer center. While this localized care allows the patient to remain close to family, friends, and familiar surroundings, elements of a comprehensive cancer care plan beyond actually treating the cancer may be lacking. Whereas individuals seeking treatment at large cancer centers may have easy access to all supportive aspects of care offered in the facility, a patient who chooses to receive cancer therapy close to home may have to piece together these elements from a variety of sources. Oftentimes, patients are simply unaware that such supportive services are necessary or even exist. One important, but often forgotten, area of adjunctive cancer care is dental oncology.
What is Dental Oncology?
Dental oncology is a focus of dentistry dedicated to meeting the unique dental and oral healthcare needs that arise as a result of the disease process of cancer and cancer therapy.3 The foundation of dental oncology, drawn from tenets of dentistry, oral medicine, and cancer care, is set upon improving the patient’s systemic health, oral health, and quality of life. Dental oncology goes beyond the scope of general dental treatment to include management of normal and problematic oral soft tissues, care for dental supporting structures and bone, and treatment of the direct and indirect oral effects of cancer therapy. The dentist committed to treating oncology patients must understand the relationship between systemic and oral health, know how cancer and cancer treatments can affect oral health, and be able to formulate and implement effective treatment strategies for acute and chronic oral conditions in this medically compromised population. While the obvious oncological concern for most dental professionals is oral cancer, the scope of dental oncology broadens this view and encompasses oral issues related to all forms of cancer.
The link between oral health and systemic health is well understood. Less familiar, however, are the ramifications modern cancer therapies can have on the oral environment. Modalities of cancer treatment can cause debilitating direct cytotoxic effects and indirect side effects that inflict pain, decrease quality of life, and at times even require an interruption or discontinuation of cancer care. The oral effects of cancer treatment can become so severe that the patient’s ability to eat is inhibited, thus jeopardizing essential nutrition. Similarly, these secondary effects can be so physically debilitating that they cause the patient to withdraw socially. Such psychosocial behavior, if allowed to continue, can diminish the patient’s desire to thrive. As the number of cancer survivors increases, it is becoming increasingly recognized that the aggressive management of oral toxicities is needed to ensure optimal long-term oral health and general well-being.4
The Oral and Systemic Effects of Cancer Therapy
Today’s cancer therapy may include surgery, chemotherapy, radiation therapy, hematopoietic cell transplantation, targeted cell therapy, or some combination thereof. Each modality of treatment, however, can affect oral health, which ultimately can affect systemic health. Deleterious effects of cancer and cancer therapies of concern to the dentist treating oncology patients include xerostomia and hyposalivation; chronic and acute oral mucositis; rampant dental caries and/or demineralization; periodontitis; oral infections, including oropharyngeal candidiasis, viral infections, and bacterial infections; osteonecrosis, subsequent to both radiation therapy and bisphosphonates; orofacial pain; trismus; taste and smell disorders; metastatic oral cancer; and psychosocial problems secondary to oral health issues.
The direct and indirect effects of cancer therapies can wreak havoc on the oral environment. The goal of chemotherapeutic agents is to eradicate the rapidly dividing cells of a tumor. Unfortunately, chemotherapy is often toxic to cells in the body that normally undergo rapid division such as the bone marrow, hair, and the mucosal cells along the entire gastrointestinal tract, including the oral cavity. The direct cytotoxic effects of chemotherapeutic drugs result in changes in the oral lining epithelium, changes to the oral vasculature, inhibition in the oral inflammatory and healing responses, and differentiation in the oral ecology.5 Direct damage from ionizing radiation occurs in patients treated with radiation for head-and-neck cancers. Indirectly, the immunosuppressive effects of cancer therapies affect the oral cavity. Suppression of the hemopoietic cells of the bone marrow results in anemia, thrombocytopenia, and neutropenia, thus increasing the risk of bleeding, oral infection, and systemic infection from an oral source.
Some of the effects of head-and-neck radiation, unlike chemotherapy, grow more degenerative over time and continue to be an issue of concern for cancer survivors for the remainder of their lives. Chronic fatigue of the neck muscles sometimes makes it difficult to keep the head upright and move the head backwards. Degeneration of the cervical spine is possible. Blockage or calcification of the carotid arteries, a long-term side effect of neck radiation, can restrict blood flow to the brain.6 From an oral health aspect, head-and-neck radiation patients are at extreme risk for ongoing oral complications. Meticulous attention must be paid to oral hygiene, often for the remainder of the patient’s life.
Xerostomia and Salivary Disorders
Xerostomia is perhaps one of the most common and problematic side effects encountered in dental oncology. Xerostomia is the patient’s subjective complaint of dry mouth that usually reflects a decreased presence of saliva.7 Hyposalivation is objectively assessed by the practitioner by measuring a patient’s stimulated and non-stimulated salivary flow.8 Interestingly, hyposalivation does not always correlate with the perception of dry mouth,9 so the dentist must be aware of the risk and follow the patient closely for signs of decreased salivary flow. Mild pharmaceutical-induced xerostomia may be amplified during cancer therapy in patients taking medication for systemic comorbidities, while high doses of chemotherapy and some targeted cell therapies can cause a reduction in salivary flow in their own right.10
Saliva is critical for several normal functions within the mouth. Saliva promotes the healing of damaged mucosa via growth factors and salivary antioxidants. It contains antimicrobial factors that protect against many bacteria and fungi.11,12 Saliva buffers the oral pH with bicarbonate and phosphate ions,7 and provides calcium and phosphate to maintain the integrity of dental enamel.13 The chemical process of digestion begins with the salivary enzyme, amylase, which aids in the breakdown of starch. Swallowing is facilitated by the presence of saliva through the formation of a bolus of food that can be easily swallowed.
Salivary glands are especially sensitive to radiation therapy. In head-and-neck radiation, patients receiving as little as 10 Gy may experience a decrease in salivary flow and doses greater than 30 Gy may result in permanent dysfunction.14 The degree of xerostomia is related to the radiation dose received by the salivary gland. Radiation of salivary glands results in atrophy of the secretory cells and subsequent reduction in salivary flow. Serous glands are more quickly degenerated by ionizing radiation than mucous glands. The result is saliva that is more acidic and thick and does not flow as readily as normal. Consequently, many patients undergoing head-and-neck radiation complain of thick or sticky saliva. These patients often describe their saliva as stringy and hard to clear. This condition generally lasts for weeks to months after the completion of treatment but may persist long term.15
The loss of normal saliva can be detrimental to oral homeostasis. Demineralization of the dentition is a likely sequela of hyposalivation. It is thought that the loss of saliva diminishes the buffering of the oral pH and decreases the availability of calcium and phosphate, ions important in the process of enamel remineralization. A reduction in the salivary antimicrobial protection may lead to a shift toward more cariogenic bacteria such as Streptococcus mutans and the Lactobacillus species.16 Sequestering remineralization and facilitating opportunistic overgrowth of cariogenic bacteria often lead to rampant caries. Rampant caries can lead to pain, infection, and even systemic illness in the immunocompromised patient. Beyond the structural damage of rampant dental caries, demineralization can lead to advanced periodontal disease and even osteoradionecrosis.17
Cariogenic bacteria are not the only microorganisms that experience overgrowth in the absence of saliva. The loss of saliva increases the propensity for non-bacterial oral infections, especially candidiasis. Oropharyngeal candidiasis is a frequent complication in immunosuppressed patients. Oral fungal infections are often described as eliciting a burning or scalding sensation.18 Oropharyngeal fungal infections can result in pain, dysgeusia, malnutrition, and esophageal infection leading to dysphagia.
Salivary loss can also lead to exaggerated tongue fissures, difficulty speaking, halitosis, oral soreness and burning, and an inability to wear dentures. Although these conditions may not directly affect systemic health, such maladies brought about by reduced saliva can have an unfavorable effect on the patient’s quality of life.19
Regardless of the etiology, moderate to severe xerostomia is a serious condition that must be addressed by the dentist committed to treating individuals battling cancer. In 1977, Dr. Ira Shannon made the following statement that still holds true today: “The maintenance of oral health in xerostomic patients is demanding for both the patient and the dentist. It requires cooperation and compliance on the part of the patient, with a commitment of time and effort well beyond that required for normal oral care. The dentist must promote and inspire this cooperation, provide detailed instructions and guidance, and follow the patient meticulously. Only in this way can the ravaging form of caries often found in these patients be prevented.”20
Mucositis
Mucositis is an inflammatory process that results from tissue damage secondary to chemotherapy or head-and-neck radiation therapy. Some chemotherapeutic agents—notably the antimetabolites, anthracyclines, alkylating agents, platinum-based agents, vinca alkaloids, and taxanes—are associated with a higher incidence and increased severity of mucositis.21 The severity of chemotherapy-induced mucositis is directly correlated to the degree of neutropenia and is most severe at the patient’s nadir, or the lowest point of immunosuppression. Mucositis in radiation patients is a factor of radiated volume-area diameter, overall treatment time, and cumulative dose.22 Clinical oral mucositis typically begins about 5 to 10 days after the initiation of the treatment regimen and usually lasts for 7 to 14 days,23 although occurrence can be prolonged up to one month.
Some patient parameters are believed to influence incidence and severity of mucositis: age and gender24; comorbid diseases such as AIDS, diabetes, and renal disease; preexisting periodontal disease25; genetic factors26; nutritional status; oral microflora; and the use of alcohol and/or tobacco. In mucositis, the submucosa, basal epithelium, and extracellular matrix are targeted, and thus the injury may not be clinically visible until the damage has progressed to an ulcerative phase.27 During the ulcerative phase, mucositis can become so debilitating that it causes the patient to quit eating or drinking, a behavior that risks systemic nutrition or dehydration and compromises the patient’s ability to fight the cancer. Fungi and bacteria, including anaerobic organisms, can colonize damaged mucosa resulting from the ulceration. This microbial assault combined with simultaneous immunosuppression is believed to be the primary source for systemic infections from an oral origin. Symptoms can even become so severe that it may become necessary to alter the patient’s treatment schedule until the mucositis is resolved.
Osteonecrosis of the Jaw
Osteoradionecrosis and bisphosphonate-related osteonecrosis of the jaw are osseous complications secondary to radiation therapy to the maxilla and/or mandible and use of bisphosphonates, respectively. Both conditions are brought about by an impaired capacity for the bone to heal. Osteoradionecrosis is a complex process that stems from changes to small blood vessels, and is usually seen in the mandible. Although it can occur after lower doses, osteoradionecrosis is most often seen in patients receiving more than 60 Gy. Osteoradionecrosis is a late effect of radiation therapy and the risk of osteoradionecrosis increases over time.28 Because of the ongoing risk of a necrotic bone event, the dentist committed to caring for patients who have a history of head-and-neck radiation should be diligent to understand the cumulative dose and what anatomical structures were affected by the radiation therapy.
Bisphosphonates are a class of drugs used to treat metastatic disease to the bone as well as osteopenia, Paget’s disease, and osteogenesis imperfecta. These drugs affect osteoclastic activity through various mechanisms of action with a similar end result of reduction of osseous resorption. Patients who have received bisphosphonates intravenously are at risk for osteonecrosis of the jaws.29 Like osteoradionecrosis, trauma to the bone (eg, extraction of a tooth) can elicit a necrosis in the bone that is very difficult to manage. Because bisphosphonates have a long half-life, in some cases up to 10 years, the dentist should be aware of a patient’s cancer care history and take precautions if therapy included the intravenous administration of bisphosphonates.
Recently, a new class of drug has been made available for conditions previously treated by bisphosphonates. Receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitors are a class of human monoclonal antibodies used in the treatment of osteoporosis, bone metastases, multiple myeloma, giant cell tumor of bone, and rheumatoid arthritis. Although RANKL inhibitors may exhibit a similar risk as bisphosphonates for necrosis, the necrosis may be less severe and respond more favorably to treatment than bisphosphonate-related osteonecrosis.30 As with bisphosphonates, the dentist caring for patients with a history of RANKL inhibitors must be aware of the risks of osteonecrosis and take appropriate steps to avoid a necrotic event.
Conclusion
Caring for patients before, during, or after their fight with cancer can be the most rewarding experience of a lifetime. More dental professionals are needed to commit to meeting the unique dental and oral healthcare needs of patients battling cancer. As epidemiological forecasts continue to predict an increase in the number of new cancer cases as well as an increase in the population of survivors and as more and more people seek care for cancer closer to home, dentists must be prepared to meet the demand of this growing population. Clearly, a dentist with an understanding of dental oncology is a valuable asset to any cancer care team.
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About the Author
Dennis M. Abbott, DDS
Dental Oncology Professionals of North Texas
Garland, Texas