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Oral Complications of Chemotherapy and Head/Neck Radiation (PDQ®): Supportive care - Health Professional Information [NCI] - Etiopathogenesis

Oral complications associated with cancer chemotherapy and radiation result from complex interactions among multiple factors. The most prominent contributors are direct lethal and sublethal damage to oral tissues, attenuation of immune and other protective systems, and interference with normal healing. Principal causes can be attributed to both direct stomatotoxicity and indirect stomatotoxicity. Direct toxicities are initiated via primary injury to oral tissues. Indirect toxicities are caused by nonoral toxicities that secondarily affect the oral cavity, including the following:

  • Myelosuppression.
  • Loss of tissue-based immune cells.
  • Loss of protective salivary constituents.

Understanding of mechanisms associated with oral complications continues to increase. Unfortunately, there are no universally effective agents or protocols to prevent toxicity. Elimination of preexisting dental/periapical, periodontal, and 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) can reduce frequency and severity of oral complications in cancer patients (refer to the Oral and Dental Management Prior to Cancer Therapy and the Management Following Cancer Therapy sections for further information).[1]

Complications can be acute (developing during therapy) or chronic (developing months to years after therapy). In general, cancer chemotherapy causes acute toxicities that resolve following discontinuation of therapy and recovery of damaged tissues. In contrast, radiation protocols typically cause not only acute oral toxicities, but induce permanent tissue damage that result in lifelong risk for the patient.

Chemotherapy-induced Complications

Risk factors for oral complications (see Table 2) derive from both direct damage to oral tissues secondary to chemotherapy and indirect damage due to regional or systemic toxicity. For example, therapy-related toxicity to oral mucosa can be exacerbated by colonizing oral microflora when local and systemic immune function is concurrently compromised. Frequency and severity of oral complications are directly related to extent and type of systemic compromise.

Table 2. Oral Complications of Cancer Chemotherapy

ComplicationDirect Risk FactorIndirect Risk Factors
DIC = disseminated intravascular coagulation; HSV = herpes simplex virus.
Oral mucositisMucosal cytotoxicityDecreased local/systemic immunity: local infections, reactivation of HSV
Physical/chemical trauma
Oral infections:  
Viral Decreased systemic immunity
Fungal Decreased oral mucosal and/or systemic immunity
Salivary gland dysfunction
Altered oral flora (decreased bacterial flora)
BacterialInadequate oral hygieneDecreased oral mucosal and/or systemic immunity
Mucosal breakdownSalivary gland dysfunction
Acquired pathogens
Taste dysfunctionTaste receptor toxicity 
XerostomiaSalivary gland toxicityAnticholinergic drugs
NeuropathiesVinca alkaloid, thalidomide, bortezomib drug use; risk for specific drug toxicity variesAnemia, dental hypersensitivity, temporomandibular dysfunction/myofascial pain
Dental and skeletal growth and development (pediatric patients)Specific drug toxicityStage of dental and skeletal maturation
Gastrointestinal mucositis causing secondary changes in oral status including taste, hygiene, and dietary intakeMucosal cytotoxicity: radiation, chemotherapyNausea and vomiting
HemorrhageOral mucositisThrombocytopenia
Physical traumaDecreased clotting factors (e.g., DIC)
Infections (e.g., HSV)
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