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Management of oral complications in irradiated head and neck cancer patients

Literature review

Hameed, Muhammad H; Zafar, Kamil; Ghafoor, Robia

doi: 10.4103/ijssr.ijssr_6_18
Review Article

The incidence of head and neck cancer is increasing and it is regarded as one of the leading causes of morbidity and mortality. The treatment of head and neck carcinoma is very challenging and depends on the stage of the disease. Radiotherapy is largely employed as primary therapy, adjuvant to surgery, or in combination with chemotherapy for the treatment of head and neck carcinomas. Patients undergoing radiotherapy are prone to a range of short- and long-term complications which adversely affects their health and quality of life. Management of these complications is complex and based on early detection, prevention, and oral care before, during, and after the treatment, to establish the best oral care pathway for these patients. Dental management of these patients is especially important to maintain oral hygiene, overall health, and nutrition status. Management involves multidisciplinary team approach which includes dental practitioners and the oncology team not only in the primary treatment but also in the long-term care and maintenance. It is, therefore, essential for clinicians involved in cancer treatment and cancer survivors to be aware of prevention and management these complications. The aim of this review is to highlight importance of postoperative complications associated with radiotherapy and to draw attention of multidisciplinary teams involved in cancer management toward dental needs of patients treated with radiation therapy, to ensure good quality care and better quality of life in irradiated head and neck cancer patients.

Department of Surgery, Aga Khan University, Aaga Khan University Hospital, Karachi, Pakistan

Department of Surgery, Aga Khan University, Aaga Khan University Hospital, Karachi, Pakistan

Department of Surgery, Aga Khan University, Aaga Khan University Hospital, Karachi, Pakistan

Address for correspondence:Muhammad Hameed, Department of Surgery, Aga Khan University, Aaga Khan University Hospital, Karachi, Pakistan

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Head and neck cancer is one of the most common malignancies and a major health concern. The annual incidence of head and neck cancers worldwide is more than 550,000 cases with around 300,000 deaths each year. 1 Approximately 90% of all malignant head and neck tumors are squamous cell carcinomas. 2 These cancers arise from the epithelial lining of the oral cavity, oropharynx, larynx, and hypopharynx. 3 , 4 The major risk factors for oral cancer are tobacco, alcohol, and areca nut. Other risk factors include radiation (e.g., sunlight and ionizing), infections (human papillomavirus), and immunodeficiency can play a role in oropharyngeal carcinoma. 5 Radiotherapy is largely employed as primary therapy, adjuvant to surgery, or in combination with chemotherapy for the treatment of oropharyngeal carcinoma. 6 Both therapies have increased cure rates, but unfortunately, they are also associated with several oral complications. 7 The intensity of these side effects is related to the dose, delivery (number of fractions), site, and mode of radiotherapy. These effects are observed above an absorbed dose of 60 Grays (Gy). 2 Management of oral complications is based on early detection, prevention, and oral care before, during, and after the treatment of cancer and requires multidisciplinary team approach which includes dental practitioners and the oncology team to establish the best oral care pathway for these patients. 8 The side effects associated with radiotherapy can be immediate such as mucositis, dysgeusia, and severe pain of varying intensities. Long-term sequelae include xerostomia, rampant caries, trismus, and osteoradionecrosis (ORN). 9 Management of these short- and long-term complications is summarized in Table 1.{Table 1}

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Complications Associated With Radiation Therapy


Oral mucositis is a common and very debilitating and painful complication of radiotherapy and chemotherapy that arises from damage to the oral mucosal lining. 1 Symptoms associated are oral erythema, pain, bleeding, and ulceration and they mostly occur during the 2 ndor 3 rdweek of radiation therapy. These symptoms lead to decreased intake of nutrients, fluids, and medications which results in increased weight loss and the need for nasogastric tube placement in these patients. 10 Patients are also at increased risk of systemic infections, including streptococcal infections and aspiration pneumonia which cause direct and indirect health-care costs and decrease quality of life. However, these symptoms are transient and last for weeks or months after completion of therapy. 9 , 11


Oral mucositis can be reduced by employing intensity-modulated radiation therapy (IMRT) which produces a custom-tailored radiation dose that limits and maximizes dose to the tumor and minimizes the dose to adjacent normal tissues, keeping radiation fields to the minimum necessary. 12 The use of benzydamine oral rinse (Difflam™, 3M Health Care) 15 milliliters 4–8 times per day during radiotherapy and up to 3 weeks after its completion has been recommended. 13 Other treatment modalities which include ice chips, antibiotics, hematopoietic growth factors, hydrolytic enzymes, and amifostine have also been advocated which is a cytoprotectant and used for prophylaxis of mucositis in those treated with concomitant chemoradiotherapy. 14 Dental health and oral hygiene are adversely affected by mucositis. Patients usually discontinue oral care because of caustic feeling when using standard toothpastes and mouthwashes. 15 The use of very soft brush along with diluted alcohol-free chlorhexidine mouthwash is advised in these patients. 14 Fluoride-containing products must be prescribed as an adjunct if the patient is able to tolerate it. Options include either high fluoride toothpaste (Duraphat 5000™, Colgate), fluoride gel (Fluorigard Gel™ [stannous fluoride 0.4% w/w] in carrier trays for 10 min/day), or alcohol-free fluoride mouth rinse. 9 , 15


Xerostomia accounts for most common long-standing problem following orofacial radiotherapy and acts as a major risk factor for the development of caries. 2 Reduction in salivary flow occurs from the 1 stweek of radiation treatment and consequently leads to long-term or permanently dry mouth. Salivary tissue is sensitive to radiation therapy, and cumulative doses above 20 Grays (Gy) are associated with the loss of up to 90% of salivary acinar cells. 16 It is particularly severe when both parotid glands are in the radiotherapy field.


It can be prevented by decreasing the radiation dose to the salivary glands, either with three-dimensional conformal radiotherapy or intensity-modulated radiotherapy (IMRT). 17 , 18 Amifostine has been used to protect against radiation-induced xerostomia; however, associated adverse effects and requirement for daily injections have limited its use. If there is unaffected salivary gland tissue, salivary stimulating agents can be used. 19 , 20 Sialogogues such as sugar-free chewing gums (xylitol) and the cholinergic agonist pilocarpine are used to stimulate remaining healthy glandular tissue which relief symptoms and may also offer some dental protection. 21 However, adverse effects of pilocarpine such as excessive perspiration, bladder and bowel motility, diarrhea, and bronchospasm may limit its use in some people. 21 , 22 In patients where there is no production of saliva even with the use of stimulating agents, salivary substitutes (glycerin and lemon, carboxymethylcellulose, or mucin) and regular nonmedicated oral rinses offer symptom relief. 23 , 24 Patients are instructed to take frequent sips of cold water/milk or other sugar-free nonacidic cool drinks. Milk lubricates and buffers acids and also contributes to enamel remineralization through its calcium and phosphate content. 25 Patients must be made aware that dry mouth is a symptom of systemic dehydration and drinking large volumes of fluid will not overcome xerostomia. In patients taking medications that cause xerostomia (antianxiety medications, antidepressants, antihypertensives, or opioid analgesics), consultation with patient's primary physician is required to reduce the dose below the threshold level. 26 Patients should also avoid caffeine because it leads to a reduction in saliva production. 27

Radiation-associated caries

Patients undergoing radiation therapy are at increased risk of developing caries because of decreased production of saliva, cariogenic diet, and the altered level of cariogenic flora. 28 In addition, effects of direct radiation on the tooth structure also weaken dentin-enamel bonds which results in microfractures, rapidly developing and aggressive lesions. 29 These lesions occur circumferentially along the cementoenamel junction and gingival margins, and most common sites involved are the labial surfaces of the cervical, cuspal, and incisor areas. 29 , 30


Management can be either preventive or restorative and prevention plays the key role. 28 , 31 Emphasis should be placed on appropriate dental hygiene measures such as regular rinses, brushing, flossing, and the management of xerostomia. 32 The use of sodium fluoride (0.05%) alcohol-free mouth rinse daily for xerostomic patients helps arrest any initial carious lesions and reduces sensitivity from preexisting areas of exposed dentin where the protective action of saliva is lost. 33 Several studies have claimed that caries can be successfully controlled by daily self-applications of 1% sodium fluoride gel in custom-made applicator trays even without dietary restrictions. 32 , 33 If fluoride alone is ineffective, then combined use of fluoride and chlorhexidine gel is recommended. 34 Chlorhexidine gel can be substituted for fluoride for 2 weeks at 3 months intervals as it has shown to keep the level of mutans streptococci under control for at least 3 months. 2 , 34

Restorative management poses many challenges because of limited access due to trismus or scarring, isolation problems due to marginal gingivitis, and altered dental substrate These problems must be taken into account during selection of appropriate restorative material. 8 Haveman et al. 35 in a study reported that there was no significant difference in caries incidence between amalgam and glass ionomers in patients who used fluoride. Wood et al. 36 studied glass ionomers and resin composite restorations in head and neck radiation patients and concluded that composite restorations frequently failed in patients who used fluoride as well as in patients who did not use fluoride. Based on these studies, both amalgam and glass ionomers are recommended restorative materials and composites are not desirable. 35 , 36 , 37

Endodontic therapy should be considered whenever possible to preserve teeth or tooth roots even if tooth has questionable prognosis and teeth should only be extracted from areas receiving <5000 cGy. 38 , 39 If extractions are obligatory from regions receiving more than 5000 cGy, consideration of hyperbaric oxygen (HBO) therapy before and after extraction is recommended. 39 , 15 Although survival rates of dental implants are negatively affected by radiotherapy, recent reviews suggest that dental implants can be considered a viable treatment option for replacement of missing teeth in head and neck radiation patients because they not only allow effective oral and facial rehabilitation but also improve the quality of life. 40 , 41 Appropriate comprehensive planning, patient selection, and timing of implant placement are essential before proceeding with treatment. 42 Several studies have reported that dental implants should be placed after a delay of 6 months after radiotherapy to allow osseointegration. 43 , 44 However, to avoid early complications of radiation therapy, most clinicians prefer to wait a minimum of 6 to12 months. 45 Others have recommended waiting a little longer (12–18 months typically) to allow enough time for bone remodeling and muscle healing. 41 , 46


ORN is defined as an area of exposed devitalized irradiated bone that fails to heal over a period of 3–6 months in the absence of local neoplastic disease. 47 , 48 It may cause pain, erythema, swelling, altered sensation, skin fistulae, and fractures or may be asymptomatic. 49 ORN is potentially a most serious long-term adverse effect of radiotherapy and its incidence varies widely in the literature ranging from 1% to 56%. 50 , 51 The risk of developing ORN is reported to be greater for the mandible compared to maxilla because mandible has relatively reduced blood supply than maxilla. 50 , 52 Development of ORN is directly related to the dose and the period for which bone is subjected to radiation. 2 , 50 Dental extractions, uncontrolled periodontal disease, wearing of removable dentures, and procedures that traumatize the mucosa along with are considered as potential causes of ORN. 53 Infection is now not considered as the primary cause of ORN; however, it occurs from radiation-triggered production of free radicals, endothelial changes, inflammation, fibrosis, and necrosis. 54 There is a high chance of superinfection of exposed bone by oral microorganisms. 55

Store and Boysen 56 described a three-stage clinical staging system of ORN:

  • Stage 0 – Only mucosal defects
  • Stage I – Intact mucosa with radiographic evidence of necrotic bone
  • Stage II – Exposed bone intraorally with radiographic evidence
  • Stage III – Clinically exposed radionecrotic bone, along with skin (extraoral) fistulas and infection.


Prevention is generally considered as the best strategy. Dental extraction is potentially considered as the main factor causing ORN in irradiated patients. Those teeth that are supposed to be extracted either due to any periodontal disease, unrestorable caries, or endodontic infections, if possible, should be extracted before radiotherapy. 55 Dental extraction of irradiated patients should be referred to secondary care for adequate management. 57 Consideration should be given to every possible chance of endodontic treatment first. If endodontic treatment is not possible, then extraction should be done as atraumatically as possible ensuring soft-tissue primary closure where possible. Limited number of teeth should be removed per appointment. 7 , 58 Dental extractions in irradiated patients require antioxidant medication, such as a combination of pentoxifylline 400 mg BID and tocopherol (Vitamin E) 1000 units daily for a minimum of 8 weeks, with 1 week preoperatively as a prophylaxis. 49 If ORN develops, the same regimen should be followed but at least for 6 months. HBO can also be employed in healing of patients with the purpose to increase blood tissue oxygen gradient. This will, in turn, stimulate fibroblast proliferation, angiogenesis, and collagen formation. 48 , 59 HBO therapy (HBOT) promotes angiogenesis and thus reduces ORN in patients undergoing extraction. HBOT involves breathing O 2under increased atmospheric pressure (22.5 atm pressure) for 1.5–2 h/day in a specially manufactured chamber. Depending on the severity of ORN, up to 80 sessions have been recommended to treat ORN. 60 , 61 Exposed nonvital bone must be excised with primary closure followed by appropriate HBOT is recommended. Recent studies concluded that HBO is associated with improvement in healing outcomes in selected patients; however, there are some economic implications and the data lack evidence for the optimum timing of therapy. 62 In summary, treatment of ORN ranges from conservative management through debridement of necrotic bone/sequestrum, resection, and closure of wound using free flaps, with or without using adjuncts' including HBO, pentoxifylline, and tocopherol Table 1. 57 , 63 , 64 , 65


Trismus is defined as limitation in mouth opening or mandibular hypomobility, i.e., <20 mm interincisal distance or approximately two finger widths. Trismus results due to contraction and fibrosis that result from surgery and radiation therapy. Although it varies from study to study, according to numerous studies, 5%–38% of patients develop trismus after receiving radiation therapy for oropharyngeal carcinoma. 66 , 67 , 68 Trismus is the factor that limits the minimally invasive operative dentistry and patient's self-care compromising patient's oral hygiene. Feeding and removable prosthesis fabrication and insertion are severely compromised as well due to limited access and range of jaw motions. Unfortunately, trismus can be progressive and so patient motivation is very important at an early stage.


Management of trismus begins with prevention rather than its treatment. 69 Patients should be advised home-based exercises to maintain maximal jaw opening and mobility as soon as radiation therapy begins. 9 , 70 There is currently lack of evidence to support the use of preradiotherapy exercise regimens to prevent or reduce the risk of trismus. There are also insufficient data in support of exercise regimens to manage trismus. 71 However, patients may get benefit from active exercises that involve the opening of jaw actively using TheraBite jaw motion rehabilitation system and a stack of wooden tongue depressors inserted between the upper and lower teeth. Numerous studies have reported the efficacy of TheraBite system in comparison with wooden spatulas and other manual stretching exercises. 72 , 73 , 74 , 75 All these kinds of exercises are patient dependent, and motivation and encouragement is essential for their success.

In case of a patient requiring dental intervention, it is useful to employ certain treatment strategies. As patient's mouth opening is already compromised, it is prudent to keep appointments short to give patient rest. A mouth prop and short-shanked burs, coupled with pediatric handpieces, may help in providing restorative care Table 1. For impression making, stock trays can be modified by the reduction of the flange areas with cutters or burs. Alternatively, fabrication of custom tray may also be advantageous. 8

Altered taste

Taste alteration can occur as a result of effect of radiation on taste buds and changes in the quality and quantity of saliva. The taste change varies from decreased ability to taste (hypoageusia) or distorted taste (dysgeusia) to inability to taste (ageusia). This loss or distortion commences at a rapid rate and aggravated once the threshold dose of 20 Gy is reached, affecting perception of all four tastes, that is, sweet, sour, salty, and bitter. 2 Loss of umami taste (which recognizes amino acids) has the greatest effect on the quality of life. 76


Taste alteration has a great impact on general health and nutritional status as it affects the choice and desire for food. 8 Taste sensation is partly restored in 4–8 weeks postradiation treatment, and in majority of patients, it is restored completely within 4 months. Nevertheless, some patients may experience permanent alteration or loss of taste. 77 A healthy diet, high sugar-containing food supplements should be prescribed to maintain caloric intake and preventing weight loss. 2

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Although radiotherapy increases the rate of survival of tumor, it is associated with adverse side effects that can even persist for life. Regular monitoring and follow-ups of these patients are required in an effort to reduce the severity of associated side effects. These patients have high susceptibility of oral disease and must be seen three times per year. After resolution of acute side effects, a strict dental hygiene care plan and preventive program must be employed. Patients' oral hygiene must be optimized through oral health education, modification of risk factors (including xerostomia and changes in nutritional needs), caries prevention regimens, fluoride supplementation, and annual caries screening radiographs.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

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78. . .;:

    Cancer of head and neck; hyperbaric oxygen therapy; intensity-modulated radiotherapy; osteoradionecrosis; xerostomia

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