Oral Effects of Cancer Care

First in a two-part series: This is the first in a two-part series exploring the oral complications of cancer treatment. Appearing in a future issue, Part 2 will focus on managing additional sequelae in this patient population.

Although cancer has typically been associated with significant mortality, therapeutic advances have increased the number of cancer survivors. However, cancer care regimens are associated with morbidity that can impact quality of life for these individuals. The purpose of this review is to discuss the oral manifestations of nonoral cancers, oral side effects of cancer therapy, and the role of dental professionals in cancer management.

Cancer has become one of the most common noncommunicable human diseases, with 43.2 million individuals living with cancer in 2014.¹ Moreover, 14.1 million new cases were diagnosed in 2012. With increasing life expectancy, this number is projected to increase to 23.6 million by 2030.¹ The negative impact of cancer treatment on oral health is a particular concern to the dental team. Yet the management of patients with cancer before, during, and after treatment presents challenges. Patients usually present with findings that either directly relate to their cancer (such as leukemia-induced gingival enlargement) or cancer treatment (such as radiation-induced xerostomia).

Oral health professionals are charged with developing individualized strategies for managing the oral complications of cancer care regimens, as 97% of patients who start chemotherapy or radiotherapy experience oral health problems.² The pre-establishment and maintenance of oral health by formulating an individualized treatment plan can help prevent or minimize the adverse consequences of cancer treatment. While these complications take many forms, this paper will limit its discussion to hyposalivation, xerostomia, taste alteration, dental caries and periodontitis. Part 2 will explore additional complications, including oral mucositis, osteoradionecrosis, candidiasis, viral infections and trismus.

The treatment of any cancer can involve a combination of modalities, but for most types it can be divided into surgery, chemotherapy and radiation. New treatment options include immunotherapy, hormone therapy, targeted drug therapy, gene therapy, nanotherapy and photodynamic therapy, among others.³

Surgery is the most established form of cancer treatment and is commonly used in combination with other interventions. The need for surgery is typically driven by the cancer’s size, location, presence of metastases, and relationship to vital structures.⁴ Surgical removal of the cancer is often accompanied by reconstructive surgery of the resected portion. Radiation therapy can be administered as a stand-alone therapy or in combination with surgery (usually for head and neck, laryngeal and uterine cancer) and chemotherapy (commonly for sarcoma, breast, esophageal, lung and rectal cancer). Radiation therapy is a successful treatment modality for cancers that are localized and encompassed within the proposed field of radiation. Radiation is also useful as a palliative treatment for inoperable cancers.⁵ Both surgery and radiation therapy, though usually localized, affect the surrounding tissues and organs.

Chemotherapy is a useful treatment modality for many cancers, including hairy cell leukemia, choriocarcinoma, acute leukemia, testicular cancer and nonHodgkin’s lymphoma. Chemotherapeutic agents can be administered either singly or as multi-agent regimens. Although chemo­therapeutic drugs are meant to target cancer cells only, most significantly impact normal cells — as well as the patient’s systemic health — as these drugs are usually administered intravenously.

From the dental team’s perspective, caring for these patients begins with pretreatment evaluation and extends to management strategies involving the short- and long-term oral sequela of cancer care regimens.

PRETREATMENT ASSESSMENT

The importance of pretreatment screening for cancer patients has been well documented.⁶ A thorough medical and dental history should be obtained, with a specific focus on the patient’s particular cancer and treatment. A discussion with the medical team is warranted to understand the nature of the cancer, as well as the timing and details of treatment.

Assessment involves a comprehensive facial and oral examination that includes soft tissues, hard tissues and lymph nodes. The intraoral examination should also look for any signs of pathology that may be a consequence of the cancer or could be exacerbated during cancer treatment (xerostomia, for example). Additionally, the focus of any infections should be identified and examined. Some of these conditions include endodontically involved teeth, untreated periodontal disease and defective restorations. Additionally, radiographic examination should be used to confirm clinical findings and rule out incipient problems and the possibility of cancer metastasis. If available, previous dental records should be reviewed.

Teeth with a hopeless prognosis (either due to caries, trauma or periodontal involvement) should be extracted before the start of cancer treatment. This is to prevent the need for emergency procedures or conditions that can be exacerbated once cancer treatment has begun. However, there is some concern that an aggressive treatment philosophy for extraction of teeth in patients undergoing cancer treatment may negatively impact their health.^7,8 Extractions should be completed at least 10 days prior to the start of cancer treatment.⁹ When appropriate, permanent restorations and prophylaxis or scaling and root planing should be performed. Additionally, the majority of patients with cancer will benefit from in-office fluoride applications. In the event cancer care cannot be delayed and therapy has to be initiated immediately, tooth extraction can be postponed until after treatment. However, the dental team should help the patient maintain optimal oral hygiene.

HYPOSALIVATION AND XEROSTOMIA

Impairment of salivary gland function and subsequent hyposalivation or xerostomia are common complications of cancer care (via both radiotherapy and use of cytostatic drugs). Cancer treatment, especially radiation to the head and neck area, can result in damage to the acinar cells and replacement of those cells with ductal and inflammatory cells.¹⁰ The quality of saliva also changes, with the saliva becoming more viscous and acidic — leading to increased plaque accumulation, overgrowth of opportunistic organisms (such as Candida albicans), and a shift in the oral microbiome toward more acidogenic bacteria.

Numerous products are available that can be used to relieve the effects of xerostomia. Adding toothpastes, gels, and mouth­rinses with a neutral pH and those containing carboxymethylcellulose to a patient’s oral hy­giene regimen may help mitigate symptoms. Toothpastes and mouthrinses with plant-based ingredients can also help soothe dry mouth symptoms.¹¹ Some evidence suggests these patients may benefit from using edible oils, such as olive or vegetable oils, as well as milk products. There are reports on the benefits of using probiotics to help in hyposalivation.¹² Although they have limited duration of action, saliva substitutes can be useful in managing the symptoms associated with dry mouth. Pilocarpine is a useful pharmacological agent that can stimulate salivary flow. Additional emerging techniques include the use of cytoprotective drugs (such as amifostine), salivary-gland-sparing radiation techniques, stem cell therapy¹³ and bioprinted nanotechnology.¹⁴

ALTERED TASTE

Taste alteration is a complication of xerostomia and radiation therapy on the taste buds. It can range from dysgeusia (altered taste) to ageusia (complete loss of taste). Sweet sensations are affected first, followed by abnormal taste, and, finally, loss of taste sensation. The reported incidence of taste alteration in patients undergoing cancer radiation is 70%.^15–17

Radiation doses greater than 30 Gy cause significant alterations that are usually restored within 20 to 60 days (except in rare cases). Additionally, chemotherapy can alter taste sensation, as patients often complain of a metallic or chemical taste due to secretion of the drug in the saliva. This side effect can lead to a general lack of interest in food intake and contribute to weight loss and nutritional deficiencies. The management of taste alteration includes increasing the seasoning and umami flavor in food.¹⁸ Zinc supplements have shown promising effects in clinical research.¹⁹ Other treatment modalities under investigation include clonazepam, dronabinol,^20–22 low-level light therapy and photobiomodulation.²³

DENTAL CARIES

Cancer patients face increased risk for dental caries during and following treatment, which can be attributed to changes in salivary flow rates, salivary composition and bacterial dysbiosis. Cancer care, especially radiotherapy to the head and neck, changes the chemical composition of saliva by decreasing pH, increasing viscosity, and decreasing its buffering capacity.²⁴ Clinically, it may present as rampant caries, with increased risk for smooth surface caries, including cusp tips, incisal edges and cervical regions.^25,26 Patients should be educated about the benefits of a noncariogenic diet and maintaining optimal oral hygiene.^27–32

Professional fluoride application, along with optimal daily doses of fluoride, are both key in reducing caries risk. Additionally, xylitol products are useful, as they can inhibit Streptococcus mutans.³³ Patients may wish to use milk and probiotic products, although there is a lack of substantial evidence to support an added benefit. The use of chlorhexidine mouthrinse has a beneficial effect, especially in patients with high streptococcal counts (> 106 colony forming units/ml of saliva). However, a recent guideline suggests that chlorhexidine should be avoided in cancer patients to prevent systemic spread of alpha-hemolytic S. viridans and Candida albicans.¹²

Products containing arginine bicarbonate and calcium carbonate may support the maintenance of a neutral pH in the oral cavity, as well as healthy enamel.³⁴ Therapies with amorphous calcium phosphate (ACP), casein phosphopeptide-ACP, calcium sodium phosphosilicate, and tricalcium phosphate may encourage remineralization and reduce caries risk.¹¹

Patients with cancer are advised to seek more frequent dental care during and after cancer treatment, as some of these effects are long lasting.

PERIODONTAL CONDITIONS

Periodontal disease is known to progress during cancer treatment, especially radiotherapy.³⁵ The periodontium is sensitive to the effects of cancer chemotherapy and radiotherapy because they not only affect the blood supply, but also the regenerative and reparative potential of the periodontium.^36,37 Additionally, xerostomia and radiation-induced caries adversely impact preexisting chronic periodontitis. Severe periodontal involvement of teeth can also lead to osteonecrosis.³⁸ Additionally, other factors, such as hematopoietic changes and superimposed infections, affect the gingiva.³⁹ Indeed, patients receiving chemotherapy can develop acute exacerbations of chronic periodontal disease due to neutropenia.^40,41 Compared with control groups, researchers have reported that oral sources of septicemia can be reduced by 50% in patients receiving professional oral prophylaxis and reinforced oral hygiene.⁴²

Pretreatment assessment and prevention are key for patients prior to starting cancer therapy. Patients undergoing chemotherapy (especially in individuals who can become neutropenic) and radiotherapy to the head and neck should receive pretreatment screening. Periodontal disease should be treated either nonsurgically or via extraction of questionable teeth (although in noncancerous patients, those teeth maybe kept under observation).³⁹ Oral hygiene instruction and monitoring are also essential before, during and after cancer care. A healing period of two weeks following dental treatment is recommended prior to the start of cancer therapy.³⁹

Some studies have dispelled the concern that periodontal maintenance increases the risk of systemic bacteremia in patients with leukemia.^42,43 There is also evidence to suggest periodontal treatment prior to the start of a cancer care regimen can reduce the risk of mucositis.⁴⁴ Antibiotic coverage for such treatment (in cases in which it cannot be delayed) should be considered if neutropenia is present and neutrophil counts are less than 500 cells/ml.

MANAGEMENT SUMMARY

A recurring theme in various practice guidelines for individuals receiving cancer treatment is they should be been seen before the start of cancer therapy and at regular recare visits (90 days or less) during the course of treatment. Although some forms of dental care should be postponed until after completing cancer treatment, maintaining oral hygiene, caries control, and managing incipient issues (as well as oral complications) should be performed during cancer treatment. Following the completion of cancer care, oral health conditions that could not be addressed previously should then be addressed.⁴⁵

Management of patients with cancer should be based on broad knowledge of the oral complications that can arise from cancer treatment, as well as an understanding of the critical roles of prevention and pretreatment screening when caring for this population. When planning dental therapy, close communication between oral health professionals and the medical team is key to establishing personalized care strategies.

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Featured image by  DIANE LABOMBARBE/E+/GETTY IMAGES PLUS

From Decisions in Dentistry. November 2018;4(11):28–30.