Cancer Therapies and Dental Considerations

Key Points

  • Given how common cancer is and the fact that cancer survival is increasing overall, it is likely that a dental health care provider will encounter people either with a history of cancer/cancer treatment or who are currently embarking on or undergoing treatment for cancer.
  • Oral complications of cancer therapy can be acute (i.e., developing during treatment) or delayed onset (i.e., developing months to years after treatment); local or systemic; or functional.
  • The most common oral complications related to cancer therapies are mucositis, opportunistic infection (viral or fungal), salivary gland dysfunction, taste disturbance, and pain.
  • The National Cancer Institute (NCI) recommends that dental professionals be considered part of the cancer care team in individuals undergoing cancer treatment and that people see their dentist 4 weeks prior to initiating cancer treatment (if possible) to allow for healing if any dental work is required.
  • The NCI considers routine, effective oral hygiene important before and throughout cancer treatment to help reduce the incidence and severity of adverse oral effects of cancer therapy.
Introduction

Cancer is a leading public health problem worldwide and is second only to cardiovascular disease as the most common cause of death in the U.S.1 Although the death rate due to cancer increased for most of the 20th century, peaking in 1991, the rate has fallen steadily since then, decreasing by 31% from 1991 to 2018.1 This decrease is attributed primarily to reductions in smoking and improvements in early detection and treatment.1 An estimated 1.9 million new cases of cancer will be diagnosed in 2022 and over 609,000 estimated deaths will occur in 2022.2

The term “cancer” is an umbrella term that includes over 100 neoplastic diseases, and includes solid tumors, multiple myeloma, leukemias, and lymphomas.3 At the start of 2022, there were over 18 million American survivors of cancer with more than half diagnosed in the prior 10 years, many affected by short-term and long-term effects of treatment.4 Among survivors, cancers were most commonly of the prostate, skin melanoma, and colon/rectum in the 8.3 million men and cancers of the breast, uterine corpus and thyroid among the 9.7 million women.4 Given how common cancer is and the fact that cancer survival is increasing overall,1 it is likely that a dental health care provider will encounter people either with a history of cancer/cancer treatment or who are currently embarking on or undergoing treatment for cancer.

Cancer Therapies and Oral Effects

Oral complications of cancer therapy can be acute (i.e., developing during treatment) or delayed onset (i.e., developing months to years after treatment); local or systemic; or functional.5, 6 Oral toxicities may be direct, e.g., treatments such as surgical procedures or radiation therapy causing damage directly to bony structures, tissues or salivary glands; or the effects may be caused indirectly, e.g., bleeding or infections caused by effects of therapies on rapidly dividing bone marrow cells or loss of protective salivary factors.6-8 Generally, cancer chemotherapy causes acute toxicity that typically resolves following discontinuation of therapy and recovery of damaged tissues, while radiation therapy can cause not only acute oral toxicities, but can induce permanent tissue damage, resulting in lifelong risk for the patient.6, 8 The most common oral complications related to cancer therapies are mucositis, opportunistic infection (viral or fungal), salivary gland dysfunction, taste disturbance, and pain.6, 8 These complications, in turn, may lead to secondary complications such as dehydration, dysgeusia (change in taste), dysphagia (difficulty swallowing), and nutritional compromise.6-8

Chemotherapy

Chemotherapy may be used alone (either as single-agent therapy or in combination regimens), or as an adjunct to radiation and/or surgery.9 Chemotherapy is generally administered parenterally; however, some chemotherapy drugs can also be administered orally. Patients receiving chemotherapy parenterally may have a catheter, port or central venous line inserted for ease of administration.10

Cytotoxic chemotherapy targets rapidly dividing cells like cancer cells but can also cause adverse effects in rapidly dividing normal tissues, like bone marrow (i.e., red and white blood cells, platelets), hair, skin, and the oral epithelium and underlying connective tissue.6, 9 Myelosuppression can cause anemia, susceptibility to infection because of neutropenia (low white cell count)9 and decreased local/systemic immunity,6 as well as increase the potential for bleeding because of a low platelet count (thrombocytopenia).9

Normal oral mucosal epithelium turns over every 9 to 16 days.6 Toxic effects of chemotherapy in the oral cavity may include ulcerative mucositis/stomatitis, xerostomia, salivary gland dysfunction, oral infections, and oral sores.7, 9 Oral infections can result in periodontal changes with advanced attachment loss and mobility.5-7, 9 Damage to salivary glands can change the volume and character of saliva, making it more viscous.5, 6 Xerostomia and reduced salivary flow can increase a person’s susceptibility to enamel demineralization and caries, particularly on root surfaces.5, 7 Reduced salivary flow can also result in chewing and swallowing difficulty. 6

Certain types of chemotherapy (e.g., vinca alkaloids) can cause dental neurotoxicity, which typically manifests as a persistent deep aching or burning pain in a tooth for which no dental or mucosal source can be found.6, 8, 9 High doses of chemotherapy in pediatric patients can cause abnormal dental development, such as altered tooth development, craniofacial growth or skeletal development, especially in those children younger than 9 years of age.8, 11

More recently developed “targeted” therapies used in cancer applications specifically interact with extracellular or intracellular molecular pathways.12, 13 Biologic agents such as monoclonal antibodies, and small-molecule inhibitors of intracellular kinases, proteasomes, epidermal growth factors, or other metabolic signaling pathways, may be used in treatment of certain cancers such as leukemias, lung, ovarian, or colon cancer.12, 13 Immunotherapies such as the “checkpoint inhibitors” pembrolizumab and nivolumab target cancer cells’ protective mechanisms, allowing the body’s own immune system to destroy the cancer cells.12, 13 These targeted agents can cause orofacial adverse effects that include stomatitis, dry mouth, oral pain or lesions, dysphagia, or dysgeusia.12, 13

High-dose bisphosphonates used to treat bone metastases or hypercalcemia of malignancy and antiangiogenic therapies used in cancers such as multiple myeloma may be associated with a specific oral adverse effect known as medication-related osteonecrosis of the jaw (MRONJ).13 More information on this topic may be found at the ADA Oral Health Topic page, “Oncology Agents and Medication-Related Osteonecrosis of the Jaw.

Radiation

Radiation, especially for head and neck cancer, can induce oral damage resulting in permanent dysfunction of vasculature, connective tissue, salivary glands, muscle, and bone.6, 14 Loss of bone vitality occurs secondary to injury to osteocytes, osteoblasts, and osteoclasts or from a relative hypoxia due to reduction in vascular supply.6 This may result in adverse effects to salivary glands; supportive structures in the mouth, jaw, and throat; and to vulnerable bony tissue (e.g., the mandible) within the radiation field.6 Unlike chemotherapy, radiation damage is anatomically site-specific; toxicity is localized to irradiated tissue volumes.6 Radiation regimen-related factors, including approach and type of radiation used, total dose administered, and field size/fractionation will have an effect on the amount of damage incurred.6 Radiation-induced damage also differs from chemotherapy-induced changes in that irradiated tissue damage tends to be permanent and puts the patient at continued risk for oral complications, including damage from subsequent toxic drug or radiation exposure; normal physiologic repair mechanisms may also be compromised as a result of the permanent cellular damage.6

Adverse effects of radiotherapy such as xerostomia, mucositis, trismus, bone exposure, dysphasia/dysgeusia, soft tissue fibrosis, and, rarely, later-stage osteoradionecrosis (ORN) of the bone may develop.6, 7 Although ORN may be associated with dental manipulations to the bone or tissue in the exposed area, it may also occur spontaneously. A 2010 systematic review of dental disease in people undergoing cancer therapy found that people who had undergone radiation therapy for head and neck cancer had the highest prevalence of decayed, missing, or filled teeth (DFMT).15 Similar to chemotherapy, radiation therapy in pediatric patients can cause abnormal dental development, such as altered tooth development, craniofacial growth or skeletal development, especially in those children younger than 9 years of age.8

Surgical Procedures

Surgical procedures such as removal of removal of the tumor and possible neck node dissection in the head and neck area may result in injury to and/or removal of muscle, bone, or glandular tissue that supports oral function such as chewing, swallowing, or salivary production.5

Stem-Cell Transplant

People with certain types of cancer may undergo autologous or allogeneic stem-cell transplant, which is a procedure in which a patient receives healthy blood-forming stem cells to replace their own diseased stem cells. The healthy stem cells may come from the blood or bone marrow of the patient themselves (autologous) or from a related or unrelated donor (allogeneic). In the past, acute systemic adverse effects of doses of chemotherapeutic drugs used to ablate the patient’s bone marrow (myeloablative) tended to be severe.5 However, current nonmyeloablative or reduced-intensity marrow-conditioning regimens tend to have fewer regimen-related toxicities.5 A specific complication of allogeneic stem-cell transplant with an oral manifestation is chronic graft-versus-host disease (cGvHD), in which the engrafted stem cells mount an immune response to the recipient’s native cells.5, 16 Patients experiencing cGvHD may present with mucosal lesions, salivary gland dysfunction, or reduction in mouth opening because of cutaneous sclerosis; patients also may experience symptoms of xerostomia, dysphagia, or oral pain.16

Dental Treatment Considerations

Pretreatment Considerations

The National Cancer Institute (NCI)6, 17 recommends that dental professionals be considered part of the cancer care team for individuals undergoing cancer treatment and that people see their dentist 4 weeks prior to initiating cancer treatment (if possible) to allow for healing if any dental work is required.6, 17 The involvement of a dental team experienced with oral oncology may reduce the risk of oral complications, either by direct examination of the patient or in consultation with the patient’s community-based dentist.6 Dental work should generally prioritize treatment of teeth that have a risk of infection or decay to help avoid the need for dental treatment during cancer treatment.6, 17 According to the NCI, there is no universally accepted pre-cancer therapy dental protocol because of the lack of clinical trials evaluating the efficacy of a specific protocol.6 However, elimination of preexisting dental/periapical, periodontal, or mucosal infections; institution of comprehensive oral hygiene protocols during therapy; and reduction of other factors that may compromise oral mucosal integrity (e.g., physical trauma to oral tissues) may help reduce frequency and severity of oral complications in cancer patients.6 In some cases, such as acute leukemia, where induction chemotherapy may begin within days of diagnosis, there may be no time to institute elective dental therapy.18 On the other hand, in some cases of solid cancers (e.g., lung, breast, prostate, or colon cancer), there may be less of a need for urgent pretreatment dental evaluation if myelosuppression (specifically, neutropenia) is anticipated to be limited in severity.18

The NCI also recommends that in people undergoing chemotherapy or hematopoietic stem cell therapy, a comprehensive plan for oral disease stabilization be established between the oncology team and dental care providers.6 This includes communication from the oncology team about cancer details (type, stage, etc.), treatment approach, blood counts, and comorbid conditions.6, 7, 9, 18 Communication from the dental provider might include data regarding active caries, periodontal or endodontic disease, teeth requiring extraction, or other urgent dental care, with the goal of treatment planning and treating or stabilizing oral disease that could potentially cause complications during cancer treatment.6, 7, 9 If the individual is unable to receive medically urgent care in the community, the oncology team may intervene with inpatient care.6

The NCI emphasizes that dental treatment plans need to be realistic, relative to the type and extent of dental disease and define how long it could be until routine dental care can be resumed.6 For example, in teeth with minor caries, conservative stabilization procedures such as aggressive topical fluoride management, temporary restorations, or dental sealants may be considered.6

General features of pretreatment dental evaluation and care may include, for example7, 9, 18:

  • thorough dental examination with radiographs and periodontal charting to establish the patient’s baseline oral health and to attempt to identify problems that may interfere with or interrupt cancer treatment;
  • institution of instruction and support for optimal oral hygiene;
  • planning for and reducing the risk for potential oral adverse effects, including infections, nutritional compromise, pain, and mucositis/xerostomia;
  • elimination of potential sources of intraoral trauma (e.g., sharp restorations, broken teeth, ill-fitting prostheses or orthodontic appliances) that may injure compromised tissues;
  • extraction of non-restorable teeth that could be sources of infection during cancer treatment;
  • taking impressions of the dentition in order to fabricate fluoride delivery trays to facilitate instituting fluoride administration in people undergoing radiation therapy for head and neck cancer;
  • educating dental patients as to what they may expect in terms of oral adverse effects of therapy, such as xerostomia or mucositis, and approaches to take to manage these adverse effects.

Dental Treatment Considerations During Active Therapy

Although as stated previously, dental care may optimally be provided prior to starting chemotherapy, dental interventions might also need to be provided during active cancer treatment.9 Consulting with the patient’s oncologist/oncology team can help to determine the patient’s current health status and ability to undergo invasive dental treatment, especially hematologic (red cell, white cell, platelet counts) status.7 In the past, recommended minimum thresholds for platelet count and neutrophil count (i.e., white count) for patients undergoing active cancer therapy to receive invasive dental procedures had been published; however, these varied based on the published source.19 The NCI has specific assessment and management recommendations relative to invasive dental procedures in people undergoing chemotherapy or hematopoietic stem-cell transplantation in Tables 3 and 4 of the online resource, “Oral Complications of Chemotherapy and Head/Neck Radiation (PDQ®) Health Professional Version.”6

Consideration may be appropriate, also in consultation with the oncology team, to empiric antibiotic prophylaxis protocols prior to invasive dental procedures in people undergoing cancer treatment, for example, those who have implanted vascular access devices, central venous catheters, or ports.6, 7, 18

Oral and Dental Manifestations and Management Considerations

Mucositis. Oral mucositis can be a painful and potentially debilitating adverse effect of cancer therapy.20-22 In severe oral mucositis, patients experience oral erythema and ulcers that can cause extreme pain and can be associated with poor oral intake and may even affect a person’s ability to tolerate optimal treatment regimens.20-23 Oral mucositis increases the risk of local and systemic infection, and can add significantly to health care resource use and cost.20, 22 General recommendations to help minimize effects of oral mucositis may include6, 21-25:

  • Maintaining good oral hygiene;
  • Avoiding hard, rough-textured, acidic, or spicy foods or alcohol;
  • Avoiding tobacco;
  • Eating soft, moist foods that are easy to swallow or eating chilled foods;
  • Using mild or non-flavored toothpastes;
  • Using saline/bland mouthrinses as often as necessary;
  • Removing prostheses if irritation, mucositis, or ulceration occurs.

More advanced measures for mucositis management may be required in patients undergoing certain chemotherapy types or high-dose chemotherapy with or without stem-cell transplant.21 The National Cancer Institute’s resource, “Oral Complications of Chemotherapy and Head/Neck Radiation (PDQ®) Health Professional Version6 outlines the details of certain more advanced interventions that may be implemented by the oncology team (e.g., palifermin therapy, oral cryotherapy at the time of chemotherapy administration).6, 26 The American Cancer Society recommends that individuals undergoing cancer therapy contact their health care team if they experience24:

  • Redness or shininess in the mouth that lasts more than 48 hours;
  • Bleeding gums;
  • A temperature of 100.5 degrees F or higher (taken by mouth);
  • White patches on the tongue or inside the mouth;
  • Little food or fluid intake for 2 days;
  • Inability to swallow medication because of mouth sores.

Normal saline solution may be prepared by adding approximately 1 teaspoon of table salt to 1 quart (4 cups) of water.6 The solution can be administered either at room temperature or refrigerated, depending on patient preference.6 The patient is generally instructed to rinse and swish approximately 1 tablespoon of the solution and spit it out; this may be repeated as often as necessary to maintain oral comfort.6 Sodium bicarbonate (baking soda) may be added (1 to 2 tablespoons per quart of water), if viscous saliva is present.6 Saline solution can enhance oral lubrication, directly, as well as by stimulating salivary glands to increase salivary flow.6

Topical corticosteroid ointments for oral use are commercially available or can be compounded by pharmacies.27 For oral lesions that can be accessed by the patient, ointment may be applied 3 to 4 times daily, using a cotton-tip applicator.27

Single-agent oral elixirs or rinses containing dexamethasone, diphenhydramine, benzydamine, or doxepin have been used to alleviate oral mucositis.27-29 In many cases, these elixirs require compounding at pharmacies.23, 30 Mixed medication mouthwashes, often referred to as “magic mouthwash” combinations, have also been used for oral mucositis;27, 30 however, many experts do not recommend them, citing a lack of evidence of efficacy.27, 30, 31 These mouthwashes consist of various combinations of anticholinergic agents (e.g., the antihistamine diphenhydramine), antacids and/or mucosal protective agents (e.g., sucralfate, aluminum hydroxide), anesthetics (e.g., lidocaine), and sometimes antibacterials, antifungals, opioids, and corticosteroids.27, 30 The NCI states that, “The use of compounded topical anesthetic rinses should be considered carefully relative to the cost of compounding these products versus their actual efficacy.”6

A systematic review of the management of oral mucositis by McGuire et al.32 concluded that there was no evidence supporting the use of mixed medication mouthwashes for management of mucositis in patients with cancer. A placebo-controlled, head-to-head comparison of doxepin mouthwash versus diphenhydramine-lidocaine-antacid mouthwash in patients undergoing head and neck radiation therapy found that although both mouthwashes with active ingredients statistically significantly reduced oral mucositis pain the first 4 hours after administration compared with placebo, the effect size was less than the minimally clinically important difference.28 The authors called for further research into the longer-term safety and efficacy of these mouthwashes,28 as did the authors of an accompanying editorial.33

Xerostomia. Cancer treatment, especially radiation therapy for head and neck cancer, may cause salivary gland hypofunction, resulting in xerostomia/dry mouth, which may be severe.34 People with severe xerostomia may be susceptible to dental caries, periodontal disease, and oral candidiasis.35 Various prevention (e.g., radioprotective agents, intensity-modulated radiotherapy) and advanced treatment strategies (e.g., surgical transfer of the submandibular gland) have been investigated.34 A systematic review and meta-analysis of the cholinergic agent pilocarpine for radiation-induced xerostomia in head and neck cancer patients found limited evidence for its use and recommended a need for further study.36

More information on this topic may be found at the ADA Oral Health Topic page, “Xerostomia (Dry Mouth).”

Osteoradionecrosis. While radiotherapy techniques for head and neck cancer have become more targeted and conformal, more effectively treating the tumor while sparing organs at risk (i.e., brainstem, salivary glands, or mandibular bone),37 osteoradionecrosis of the jaw (ORNJ) remains a potentially severe risk of this therapy.35, 37 ORNJ is hypothesized to result from radiation injury to bone within the irradiated field causing it to become hypovascular and hypoxic, leading to aseptic, avascular necrosis and increased risk for infection, tooth loss and jaw fracture.38 ORNJ occurs rarely in people receiving less than 6000 centiGrays (cGy) of radiation and generally occurs months or years following radiotherapy.38, 39 ORNJ is often associated with pain and morbidity, is difficult to treat, and may require surgical resection and reconstruction for management.40

Prevalence estimates for ORNJ range from 2% to 15%.35, 39-42 The range, may in part, reflect differences in lesion definition; as a recent study of 572 individuals undergoing radiotherapy for head and neck cancer, reported a 6.1% incidence of exposed bone, but an incidence rate of ORNJ of 3.1%.43

Although there is an association of surgical dental interventions such as extractions or other procedures where bone or soft tissue is manipulated with the development of postradiotherapy ORNJ, whether dental intervention prior to radiotherapy is associated with lower rates of post-RT ORNJ is unclear.44 A recent systematic review and meta-analysis found mostly very low certainty evidence suggesting that patients with head and neck cancer who need dental intervention prior to radiation therapy may have an increased risk of developing ORNJ compared to those who do not.44 Maintaining optimal oral health may help reduce the need for urgent preradiotherapy dental treatment, potentially reducing ORNJ risk and minimizing delay of oncologic treatment in patients with head and neck cancer.44

Oral Lesions. Patients undergoing therapies for cancer may present with opportunistic oral infections because of their immunocompromised status.18 Viral infections such as exacerbation of oral or perioral herpes simplex virus or varicella zoster virus may require systemic antiviral therapy.9, 18 Presence of oral candidiasis (thrush, angular cheilitis, erythematous candidiasis) or deep fungal infections may be treated with topical or systemic antifungal medications, depending on the site and extent of the infection.9, 18

Chronic Graft Versus Host Disease (cGvHD). Specific management strategies for dental/oral manifestations of cGvHD may include5:

  • Antivirals or antifungals for localized infections;
  • Topical corticosteroids, retinoic acid, or immunomodulators (e.g., cyclosporine, azathioprine)
  • Psoralen plus ultraviolet A therapy (PUVA)
  • Symptom management: mucosal coating agents, anesthetics, analgesics, sialagogues, salivary substitutes
  • Fibrosis management: physical therapy

Hygiene and Home Oral Care Practices During and After Treatment

The NCI considers routine, effective oral hygiene important before and throughout cancer treatment to help reduce the incidence and severity of adverse oral effects of cancer therapy.6 Patients should be instructed to use a soft, nylon-bristled toothbrush (powered toothbrushes may be used if the patient is able to use them without causing trauma) and a mild-flavored fluoride toothpaste twice daily, rinsing frequently.6, 7, 9 If a patient cannot use a conventional toothbrush, foam toothbrushes may be used; in cases where routine brushing and interdental cleaning is not possible, antimicrobial rinses may be used.6 If toothpaste is not tolerated, 0.9% saline or water may be used, instead.6 It is recommended that mouthrinses containing alcohol be avoided.7

Interdental cleaning using atraumatic technique or less-traumatic interventions such as waxed floss or dental tape, should be done once daily.6, 7, 9 Fluoride gel products (1.1% neutral sodium fluoride or 0.4% unflavored stannous fluoride) can be used once daily for 2 to 3 minutes.6, 7 Bland mouthrinses such as 0.9% saline, sodium bicarbonate solution, or a mixture of the two can be used every 2 to 4 hours or as needed to alleviate mouth discomfort.6 Hydrogen peroxide solutions are not recommended for daily rinsing.6, 9 Patients with dry mouth may benefit from frequent sipping of water, sucking on ice chips or sugar-free candy, or chewing sugar-free gum; use of artificial saliva substitutes may also be considered.7

Dental Considerations Following Completion of Cancer Treatment

Following completion of cancer therapy, dental patients may have long-lasting residual oral effects, such as dry mouth, increased caries risk, or, rarely, latent adverse effects such as osteoradionecrosis of the jaw. Adult survivors of childhood cancer may be at increased risk for poor oral and dental health because of late effects of treatment.11, 45 Early identification of oral and dental morbidity and early interventions can help optimize health and quality of life.11, 45 Dental health care providers can take a proactive approach in identifying those people who may be at increased risk because of past cancer treatment with health histories and actively monitor patients for adverse sequelae or other treatment-related interventions (e.g., routine use of dental fluoride gels or high-concentration fluoride dentifrices). Following completion of cancer therapy, patients should be encouraged to maintain a normal dental recall schedule and maintenance of optimal oral health.9

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Other Resources

National Institute of Dental and Craniofacial Research (NIDCR):

Dental Provider’s Oncology Pocket Guide (Archived; Reprinted September 2009)
Oral Complications of Cancer Treatment: What the Dental Team Can Do (NIH Publication No. 09–4372; Reprinted September 2009)
Oncology Pocket Guide to Oral Health (Reprinted September 2009)
Three Good Reasons to See A Dentist Before Cancer Treatment (NIH Publication No. 14-5172 August 2014)

National Cancer Institute:

Oral Complications of Chemotherapy and Head/Neck Radiation (PDQ®)–Health Professional Version (Last Updated: July 14, 2021)
Oral Complications of Chemotherapy and Head/Neck Radiation (PDQ®)–Patient Version (Last Updated: April 26, 2019)

American Cancer Society:

Mouth Dryness or Thick Saliva (Last Revised: February 1, 2020)
Mouth Sores and Pain (Last Revised: September 24, 2021)

Last Updated: August 30, 2022

Prepared by:

Department of Scientific Information, Evidence Synthesis & Translation Research, ADA Science & Research Institute, LLC.

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