According to the National Cancer Institute, approximately 1.7 million new cases of cancer were diagnosed, and 600,000 people died of cancer in the US in 2014.1 The number of cancer patients increases each year, and, as is obvious, the number of living cancer patients continues to grow. That also means that the percentage of cancer patients in the dental practice continues to rise.

All of us know that cancer therapies can cause adverse effects, including hair loss, nausea, and vomiting, etc. However, many people, including dental professionals, are not aware of the especially morbid adverse effects that cancer and cancer therapies can cause in the mouth. These include xerostomia and candidiasis, but also the more damaging and painful oral mucositis. These side effects of therapy can have serious consequences on quality of life, and even survival, of cancer patients.

It is thus important to understand the oral care needs of these patients, and the role dental hygienists can, and should, play in their care. Hygienists can help treat or even prevent these conditions, and perhaps even more importantly, can teach patients steps they can take to help prevent or reduce their severity.

Xerostomia

Xerostomia (dry mouth) is a problem that is increasingly more prevalent in the general population and is a major issue in cancer patients. It is estimated that 20% of Americans suffer from dry mouth. Those numbers are higher in the elderly population where xerostomia affects up to 50% of elderly Americans. Sali- vary glands produce less saliva as we age. Furthermore, most elderly people take daily medications for various conditions, and an estimated 80% of commonly prescribed drugs are known to cause dry mouth. These include medications such as antihistamines, prescription pain medications, drugs for heartburn or acid reflux, high blood pressure, depression, anxiety, and others.2

Head and neck radiation therapy, and many chemotherapy drugs, are notorious for causing dry mouth. Chemotherapeutic drugs can alter salivary gland function and make saliva thicker. They can also damage salivary glands and result in permanent xerostomia, and radiotherapy can damage or even destroy salivary glands.3 Indeed, quality of life in 40% of head and neck cancer patients who undergo radiotherapy is severely impaired due to dry mouth from salivary gland damage.4 Xerostomia can be so severe that people wake up with their tongues stuck to the roof of their mouth or their lips stuck to their teeth, and they have to force water into their mouths to help free attached tissues. They can- not swallow food without sipping water or some other liquid to wet the food. Many people avoid certain foods altogether. Dry mouth can cause other uncomfortable situations, such as an altered sense of taste or difficulty speaking and sleeping. Because of reduced salivary functions, more serious problems can include tooth decay, periodontitis, cracked lips and cheeks, painful tongue, mouth ulcers, and fungal infections. Xerostomia is a contributor to malnutrition in the elderly. All of these conditions can be especially serious in cancer patients who are more susceptible to secondary infections, and for whom a good nutritional status is extremely important.2,5

Xerostomia patients should be instructed to avoid products that can exacerbate dryness, such as alcohol and caffeine-containing products. Salivary substitutes, such as sugarless gums, lozenges, sprays, and rinses may help. However, these products are not therapeutic and do not adequately reduce the risk of oral disease, including caries and periodontitis, which is a serious problem in cancer patients. Good oral hygiene is therefore extremely important, and emphasis should be placed on hygiene procedures practiced throughout the day. Regular professional application of fluoride rinses and daily use of prescription fluoride toothpaste is recommended. Mouth rinses are ideal additions to the daily regimen to help reduce gin- givitis.6,7

Candidiasis

Candida albicans is a fungus commonly found in the mouth (other candida species may also inhabit the mouth, and can cause the problems discussed below; however, C. albicans is the species most commonly involved). Overgrowth of C. albicans results in the infection, candidiasis, and can be an especially serious problem in cancer patients because chemo- and radiotherapy is a major cause of candidiasis. Oral candidiasis (thrush) is also commonly associated with xerostomia.8,9

Oral candidiasis can cause a burning sensation and alter the sense of taste. It is also associated with angular cheilitis (fissures in the corners of the mouth). Candidiasis lesions can bleed and be painful. In normal, healthy people, oral candidiasis usually causes no serious problems. However, in cancer patients, whose immune systems are usually suppressed, much more serious, and even life-threatening, issues may arise. Candida can spread to the intestines and interfere with receiving adequate nutrition, which can be much more consequential in cancer patients than in healthy people. It can also enter the bloodstream and cause disseminated candidiasis that can affect the brain, lungs, liver, heart valves, and other organs. The mortality rate of these gravely ill patients varies with the type of cancer involved, but, not surprisingly, can be well over 50%.10

Treatment of oral candidiasis involves anti-fungal agents taken orally or used topically. Unfortunately, many anti-fungal agents are relatively cytotoxic and damage host cells and many candida species have developed resistance to these agents.10 Prevention of oral candidiasis involves good oral hygiene to help keep the oral fungal population under control. Denture care is not always a major concern of hygienists, but, with these patients, it is extremely important. Because dentures are a “haven” for plaque, cancer patients must understand the need to be fastidious in their denture care. Oral rinses are recommended for use several times each day for all cancer patients and can be especially important with denture wearers. A good diet is vital, and a reduction of sugar and yeast-containing foods is also important.

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BRONJ

Another oral condition related to cancer therapies is bisphosphonate-related osteonecrosis of the jaw (BRONJ or BON). A newer term is now coming into use, medication-related osteonecrosis of the jaw; MRONJ, like other medications, can also cause this condition. These include other anti-resorptive medications and anti-angiogenic medications used in cancer therapy. This discussion will center on BRONJ, but prevention and treatment are identical for all these conditions. Bisphosphonates are anti-resorptive medications used to prevent bone loss due to a variety of conditions. These include osteoporosis, osteogenesis imperfecta (brittle bone disease), primary hyperparathyroidism, Paget's disease, and others. Intravenous bisphosphonates are also used to prevent bone metastasis and/or pain in various cancers such as those of breast, lung, and prostate, and to prevent lytic lesions of the skull and spine from the plasma cell cancer, multiple myeloma.11 Bisphosphonates work because they are toxic to osteoclasts, cells important for normal bone remodeling. The goal is to prevent the demineralization of bone, increase bone density and strength, and thus hopefully prevent fracture. Bisphosphonates must be taken for several months before benefits are seen. The true incidence of BRONJ is yet to be determined. The reported ranges of incidence are wide. Fortunately, BRONJ occurs in a small percentage of patients on oral bisphosphonates (0.1-0.4%); however, the range for those on IV bisphosphonates (usually cancer patients) is ~1-12%.11 Long- term use increases the chance of BRONJ. Ironically, fractures of long bones, usually the femur, can result from the use of these drugs. The reasons for this are not clear, but this is most often seen in patients who have been taking these drugs for several years.

The exact cause for BRONJ is not clear, but it is known that in addition to their effects on bone cells, bisphosphonates are also toxic to fibroblasts and keratinocytes, cells that are important in the health of soft tissues such as oral mucosa. BRONJ usually occurs after dental procedures such as tooth extraction or periodontal procedures, where surgical wounds require healing. But because bone and soft tissue cells have been exposed to these toxic drugs, these tissues can- not heal properly. The result is exposed to the bone, with pain and lack of healing of both bone and soft tissue.11
To help prevent BRONJ, these patients should have dental procedures (especially surgery) performed before initiation of bisphosphonate therapy and should be placed on a 3-month recall regimen for professional oral hygiene to keep the mouth as clean and healthy as possible. Good home care should be stressed.

When BRONJ does occur, because of exposed bone, secondary infection is a significant concern for these patients. Treatment of BRONJ, therefore, centers on the prevention of secondary infection (as well as pain relief). These patients may need to be placed on systemic antibiotics. They obviously need to practice good oral hygiene, i.e. flossing and brushing. Oral rinses are also recommended to help inhibit oral microbial growth.11

Oral Mucositis

Of all the side effects commonly associated with cancer therapies, the most morbid and debilitating is oral mucositis. Oral mucositis can result from both chemo- and radiotherapy. The etiology is complex. In simple terms, chemotherapeutic agents and/or radiation damage the DNA of the basal cells of the mucosa. This causes cell death and release of inflammatory cytokines, chemicals secreted by immune cells. Tissue damage results and ulcers usually appear 5-8 days after initiation of treatment. Oral mucositis is extremely painful and can even result in the suspension of cancer therapy because patients are unable to eat or drink.

About 40% of chemo- and/or radiotherapy patients, 80% of bone marrow and stem cell transplant patients, and the majority of head and neck cancer patients who receive radiation therapy will develop mucositis.12 Even worse, between 5 and 15% of patients on chemotherapy, and approximately 50% of patients receiving radiation to the head and neck, will develop grade 3 or 4 mucositides.13 Because of intense pain, these patients are either on a liquid diet only (grade 3) or can- not swallow anything at all (grade 4). (see photos) This can result in hospitalization and/or suspension of cancer therapy.14

To complicate matters, oral mucositis is almost always accompanied by xerostomia, which contributes to discomfort. In addition, because these patients have multiple ulcerations and are almost always immunocompromized, they are subject to secondary infections from oral bacteria, fungi, and viruses.

A variety of treatments are used for mucositis, including those for pain relief, oral hydration, and antimicrobial activity. Agents ranging from saltwater rinses to antimicrobial rinses and antimicrobial agents are common. A “Magic Mouthwash” combination “cocktail” is used by many clinics. Each clinic tends to have its own recipe, but each Magic Mouthwash cocktail usually contains an antimicrobial agent, an anti-inflammatory drug, a topical anesthetic, and a cytoprotective agent used to cover and protect the affected tissue. Unfortunate- ly, no standard treatment has proven to be satisfactory for pain relief.15

Little progress has been made in the reduction of incidence of mucositis. However, two recent studies demonstrated that professional oral hygiene procedures did significantly reduce the incidence of oral mucositis.12,13 Although oral microbes are not directly involved in the development of oral mucositis, it is clear from these studies that clean, healthy tissues are less likely to break down than are unhealthy tissues. It should be noted that both these studies involved weekly professional hygiene procedures. Cancer is expensive and time- consuming, and weekly visits to the hygienist is not a likely scenario for the vast majority of patients. Therefore, as above, good home care must be stressed with these patients.

The Dental Hygienist - First Line of Defense

Cancer patients must be educated about the potential adverse oral effects of cancer therapies. Unfortunately, oncology doctors and nurses do not always do an adequate job in this regard. Because most, or at least many, patients are on a routine professional oral hygiene regimen, they spend much more time with the hygienist than the dentist. It is therefore incumbent upon the hygienist to take the lead in the education of cancer patients about the potential oral side effects of therapy and steps the patient can take to help prevent, or at least reduce the severity, of these morbid conditions. Professional oral hygiene should be performed regularly, and excellent home care should be taught and stressed.
As mentioned several times above, oral rinses are an important option for these patients. They require no manual dexterity, can help cleanse all areas of the mouth, and are generally effective in killing oral pathogens. Unfortunately, none of these products should be swallowed due to potential toxicities. Also, almost all contain harsh chemicals, such as alcohol and other ingredients, that can cause unwanted side effects, including, ironically, many of those associated with cancer therapy. Some of these are dry mouth, burning mouth, and mouth sores. Prescription antimicrobial rinses that contain chlorhexidine are often prescribed. While very effective, common side effects of chlorhexidine include all of the above, as well as an altered sense of taste (sometimes permanent). Less common adverse effects include blistering, ulceration, or swelling of face, hands or feet, and even life-threatening anaphylactic shock.

Standard oral rinses are designed to only address microbial populations in the mouth. They do not alleviate pain or aid in healing. In fact, many of these products may actually slow the healing process because they contain ingredients that are extremely toxic to the cells involved in wound healing.16-18 What has been needed is an oral rinse that is safe to swallow, is non-toxic, and that addresses pain, microbial populations, and wound healing. Research has shown that certain food ingredients are able to provide these benefits.

Foods/Nutrients as Oral Rinses

Acemannan is a complex carbohydrate found in Aloe vera. It binds sodium ions readily and helps inhibit the pain impulse. It also enhances the healing process by stimulating macrophage activities. Studies with acemannan have demonstrated faster healing in both animals and humans.
Essential oils are natural preservatives found in various food plants. When two or more of these oils are combined they act synergistically and have antimicrobial activities against bacteria, fungi, and viruses.
Xylitol is an alcohol sugar that has been used for years as a sugar substitute because it is safe for diabetics. Xylitol does not promote dental caries because xylitol most plaque bacteria cannot ferment xylitol to caries-producing metabolic end-products, and it prevents bacterial colonization (biofilm formation), of certain bacterial species that cause decay.19,20

An oral rinse that consists entirely of plant-based food ingredients (mannose polysaccharides (acemannan), essential oils, and xylitol) in water was shown to be very effective against bacterial and fungal species found in the mouth (see chart). A gel formulation of ingredients with identical properties also demonstrated significant pain relief following tooth extraction.21 In addition, mannose polysaccharides (acemannan) promote wound healing.22,23

The use of topically applied natural food ingredients to help promote healthier mouths represents a new paradigm in oral care and portends a new era of safe, effective care for all dental patients, including those with cancer. They can provide three important benefits: pain relief, protection of oral lesions and wounds from contamination, and promotion of healing.
In conclusion, cancer therapies can cause serious adverse events in the mouth. These can affect not only quality of life, but can also be life-threatening. Good oral hygiene is critical in reducing the incidence, as well as the severity of these side effects. The dental hygienist is thus in a position to play a critical role in the overall care of these cancer patients.

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Dental hygienists must be aware of the common adverse effects of cancer therapy on oral tissues and be willing and able to teach patients how to best prevent and/or treat these conditions.​

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References
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