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Prevention and management of hard- and soft-tissue complication in patient undergoing radiotherapy and chemotherapy

Literature review

Gul, Meisha; Badar, Sheikh B; Ghafoor, Robia

doi: 10.4103/ijssr.ijssr_7_18
Review Article
Free
SDC

Head and neck cancer is among the leading causes of death globally. Its treatment includes surgical resection, radiotherapy, chemotherapy, or the combination of these therapies depending on the extent of disease. Radiotherapy and chemotherapy have a pivotal role in minimizing the morbidity and mortality; however, they also bring about many adverse effects. Both hard and soft tissues of the oral cavity are affected by these therapies ranging from oral mucositis to osteoradionecrosis of jaw thus affecting the quality of life of patients. Prevention and timely management of these complications are essential for better treatment outcomes. The present literature review, therefore, focuses on the prevention and management of hard- and soft-tissue complications associated with patients undergoing radiotherapy and chemotherapy. Comprehensive oral and dental examination of the patient should be performed and all the potential sources of infection should be electively treated appropriately before initiation of the radiotherapy and chemotherapy to reduce the risk of complications associated with the cancer treatment. Management of complication that arises during radiation and chemotherapy is also essential which requires thorough knowledge and skills. Mutual participation of oncology team and dental surgeon is the key to reduce these complications.

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

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

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

Address for correspondence:Meisha Gul, Department of Surgery, Aga Khan University, Aga Khan University Hospital, Karachi, Pakistan meishagul@gmail.com

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Introduction

Cancer comprises of extensive burden on the society, and its occurrence is increasing due to aging and growth of the world population. 1 Head and neck cancer is one of the leading cancers throughout the world. 2 It accounts for >550,000 cases and 380,000 deaths annually. 3 The management of cancer patients presents a challenge from dental perspective. The management of cancer includes surgical resection, radiotherapy, chemotherapy, or the combination of these therapies. The radiation doses for head and neck cancer depend on the size and site of tumor; it ranges from 19.2 Gy to 70 Gy. 4 Radiation dose of 30 Gy impairs the proliferation of osteoblastic cells. Radiation dose >50 Gy can cause intravascular or perivascular fibrosis leading to obliterating endarteritis. 5 Therefore, patients requiring radiation therapy and chemotherapy pose threat to the acute conditions during active cancer therapy. 6 , 7

A detailed comprehensive oral examination should be carried out before the initiation of the therapy along with radiographic assessment, using a dental panoramic radiograph (orthopantomogram), which help in the assessment of third molars and will give the global condition of the periodontal and endodontic status of the patient. 6 , 8 , 9 This panoramic radiograph should be assisted with area-specific periapical or bitewing radiographs depending on the need. 8 The focus of dental practitioner should be to identify and remove potential sources of infection in the oral cavity. 6 The dentist should provide preventive advices and perform necessary fillings, oral prophylaxis, and extractions. 10 Beside the pretreatment dental care, management of complication that arises during radiation and chemotherapy is also essential which requires thorough knowledge and skills. These complications can be broadly classified into hard-tissue and soft-tissue complications.

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Hard-Tissue Complications

Hard-tissue complications arise due to decreased protective action of saliva, increased bacterial load, inability to maintain good oral hygiene, and suppressed immunity. Complications include dental caries and osteoradionecrosis (ORN).

Dental caries

Teeth with small carious lesions can be treated with simple restorations while teeth with irreversible pulpitis or periapical pathosis may require an alteration from the conventional treatment. Ideally, a delay of at least 7 days should be sought between endodontic therapy and onset of chemotherapy. 10 Fluoride application should be performed, and if time does not permit definitive restoration, then provisional glass ionomer restorations should be carried out. 11 For effective remineralization, the literature supports the use of remineralization products containing casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) for the most effective caries remineralization and caries prevention. 12 , 13 , 14 The CPP-ACP readily incorporates fluoride ions, forming casein phosphopeptide-amorphous calcium fluoride phosphate, and this leads to the emergence of products which would be preferred for patients use from the initial workup to the posttreatment maintenance. 15 Guidelines for caries management are given in Table 1.{Table 1}

One of the most difficult aspects of the treatment phase is the management of severe caries and teeth with endodontic pathology. If the patient's blood profile is acceptable and sufficient time exists for healing of the extraction sites, removal of chronically infected or exfoliating deciduous teeth and endodontically compromised nonrestorable permanent teeth can be contemplated. Ideally, extractions should be taken place 7–10 days before the commencement of radiotherapy or chemotherapy and sufficient time should be provided for adequate healing. 16 , 17 , 18 , 19 It should be supported with the prophylactic antibiotics when the granulocytes count is <2000/mm 3, and platelet transfusion should be considered if the platelet count is <40,000/mm. 3 , 6 Table 2.{Table 2}

A minimally traumatic surgical approach with alveolectomy should be carried out for primary closure with appropriate suturing technique. Extractions should be carried out as part of plan developed with full collaboration of oncology team rather than just the decision of the dental practitioner. Decisions regarding the removal of tooth are important in patients undergoing radiotherapy of head and neck region. The patient should be evaluated carefully for any broken down and unrestorable tooth before initiating the radiotherapy. Several guidelines exist for this decision-making because the key issue is the prevention of ORN after commencement of extraction in postradiotherapy. 20 , 21 , 22 , 23

The guidelines were proposed for endodontic treatment 24 and extractions 24 as shown in Table 1and Table 2, respectively. These guidelines varied greatly among different centers and remain debatable due to lack of proper outcome-oriented randomized controlled trial. Ultimately, the decision on the type of dental treatment provided was based on the dental practitioner assessment and judgment of the present clinical and radiographical status of the patient. Experts also concluded that studies should be conducted to evaluate the risk-benefit ratio of dental procedure before the chemotherapy and radiotherapy. Further studies should be carried out to evaluate the effect of periodontal, dental, and pericoronal diseases on complications during the cancer treatment. 25

Osteoradionecrosis

ORN develops due to radiation-induced hypovascular, hypocellular, and hypoxic changes that lead to deterioration of bone, clinically presents initially as lysis of bone covered with mucosa and gingiva. 26 Healing occurs by sequestration of damaged bone. In case of soft-tissue break down, exposed bone becomes contaminated. More aggressive form can occur as a result of complication after surgery or dental extraction, producing extreme pain or even bone fracture, and requires extensive resection. Antibiotic treatment and local debridement can be helpful if diagnosed earlier; high-pressure oxygen along with necrotic bone removal is indicated in severely diseased patients. 27 , 28

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Soft-Tissue Complications

Effects of radiation on oral soft tissues include mucositis, periodontitis, impaired tissue healing, infection, taste loss, xerostomia, and esophagitis leading to nutritional impairment and ultimately affect the quality of life. 29 Among all, management of mucositis is the most important.

Oral mucositis

It occurs in up to 80% of the patients undergoing radiotherapy. 30 After exposure to radiation, acute inflammation starts within 7–98 days involving tongue, palate, oral mucosa, and pharynx and is regarded as a normal tissue injury. 30 Major risk factors associated with this condition include bad oral hygiene, poor nutritional status, smoking, concomitant chemotherapy, and lack of antibiotic use at early stage mucositis. 31 Typical presentation includes erythema, swelling, ulceration, atrophy, and pseudomembrane formation, usually accompanied by bacterial and fungal colonization. 32 It has a significant impact on health and interruption in radiation session and also increase cost for the patients. 33

Management

Management of mucositis can be divided into preventive and symptomatic treatments that mainly focus on oral hygiene maintenance and mucosal protection and topical and systemic agents to reduce pain and discomfort and antimicrobial agents Table 3a and Table 3b.{Table 3}{Table 4}

Periodontal complications

Oral hygiene instructions should be emphasized with demonstration of correct tooth brushing method and use of interdental cleaning aid. Oral prophylaxis, polishing of restorations, evaluation and management of overhanging restorations and sharp edges should be carried out to maximize the gingival and periodontal health. 6 , 11 Impression should be taken for fabrication of mouth guard is also important. Denture should be well fitting, free of any sharp corners to reduce the risk of trauma leading to ulceration. 11 The triclosan dentifrices use results in reduction of gingival inflammation and plaque and delays the progress of periodontitis. 56 , 57 , 58

Xerostomia and other complications

When salivary glands are within field of radiation, irreversible salivary glands damage occurs in 63%–93% of the patients. 59 This results in dry mouth, difficulty in chewing, swallowing, speech, altered taste sensation and increased risk of infections.

When salivary gland is not completely damaged, salivary stimulants can be used such as sialogogue medications (such as pilocarpine and cevimeline) and sugar-free gums containing xylitol. Salivary substitutes can also be used such as animal mucin, carboxymethylcellulose, and artificial saliva (Hypozalix) enzyme-enriched mouth care products. Other modalities include hyperthermic, supersaturated humidification, low-level laser therapy, acupuncture, herbal compound containing alcea digitata powder and malva sylvestris and stem cell replacement. 60 , 61 , 62 Altered taste affects patient nutrition and has significant effect on quality of life. 63 Taste gradually becomes normal, few months after therapy. 64 Cancer treatments often suppress the patient's immune system, which results in infections by opportunistic microorganisms often leading to septicemia. 65 Management includes meticulous oral hygiene and use of antimicrobial agents Table 4.{Table 5} 72

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Conclusion

Dentist plays an important role in health-care management of cancer patients. Detailed dental evaluation of these patients should be done before starting radiotherapy and chemotherapy to reduce morbidity. Proper treatment plan should be made with mutual understanding of oncology team and dental surgeon to provide care that is best on the part of patient care and to reduce complications that arise during and after the definitive treatment phase.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

1. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A, et al Global cancer statistics, 2012 CA Cancer J Clin. 2015;65:87–108
2. Sankaranarayanan R, Masuyer E, Swaminathan R, Ferlay J, Whelan S. Head and neck cancer: A global perspective on epidemiology and prognosis Anticancer Res. 1998;18:4779–86
3. Global Burden of Disease Cancer Collaboration, Fitzmaurice C, Allen C, Barber RM, Barregard L, Bhutta ZA, et al Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years for 32 cancer groups, 1990 to 2015: A Systematic analysis for the global burden of disease study JAMA Oncol. 2017;3:524–48
4. Lambert EM, Gunn GB, Gidley PW. Effects of radiation on the temporal bone in patients with head and neck cancer Head Neck. 2016;38:1428–35
5. Williams HJ, Davies AM. The effect of X-rays on bone: A pictorial review Eur Radiol. 2006;16:619–33
6. Walsh LJ. Clinical assessment and management of the oral environment in the oncology patient Aust Dent J. 2010;55 Suppl 1:66–77
7. Kelly SL, Jackson JE, Hickey BE, Szallasi FG, Bond CA. Multidisciplinary clinic care improves adherence to best practice in head and neck cancer Am J Otolaryngol. 2013;34:57–60
8. Bishay N, Petrikowski CG, Maxymiw WG, Lee L, Wood RE. Optimum dental radiography in bone marrow transplant patients Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1999;87:375–9
9. Donker AE, van Merkesteyn JP, Bredius RG, van Weel-Sipman MH. Value of panoramic radiographs in paediatric pre-bone marrow transplantation oral evaluation Int J Oral Maxillofac Surg. 2002;31:170–2
10. Athanassiadis B, Abbott PV, Walsh LJ. The use of calcium hydroxide, antibiotics and biocides as antimicrobial medicaments in endodontics Aust Dent J. 2007;52:S64–82
11. Beech N, Robinson S, Porceddu S, Batstone M. Dental management of patients irradiated for head and neck cancer Aust Dent J. 2014;59:20–8
12. Reynolds EC. Calcium phosphate-based remineralization systems: Scientific evidence? Aust Dent J. 2008;53:268–73
13. Llena C, Forner L, Baca P. Anticariogenicity of casein phosphopeptide-amorphous calcium phosphate: A review of the literature J Contemp Dent Pract. 2009;10:1–9
14. Neuhaus KW, Lussi A. Casein phosphopeptide – Amorphous calcium phosphate (CPP-ACP) and its effect on dental hard tissues Schweiz Monatsschr Zahnmed. 2009;119:110–6
15. Cross KJ, Huq NL, Reynolds EC. Casein phosphopeptides in oral health – Chemistry and clinical applications Curr Pharm Des. 2007;13:793–800
16. Mainali A, Sumanth KN, Ongole R, Denny C. Dental consultation in patients planned for/undergoing/post radiation therapy for head and neck cancers: A questionnaire-based survey Indian J Dent Res. 2011;22:669–72
17. Rothstein JP. Radiation therapy and oral care Dent Today. 2005;24:66
18. Ben-David MA, Diamante M, Radawski JD, Vineberg KA, Stroup C, Murdoch-Kinch CA, et al Lack of osteoradionecrosis of the mandible after intensity-modulated radiotherapy for head and neck cancer: Likely contributions of both dental care and improved dose distributions Int J Radiat Oncol Biol Phys. 2007;68:396–402
19. Wahl MJ. Osteoradionecrosis prevention myths Int J Radiat Oncol Biol Phys. 2006;64:661–9
20. Andrews N, Griffiths C. Dental complications of head and neck radiotherapy: Part 2 Aust Dent J. 2001;46:174–82
21. Andrews N, Griffiths C. Dental complications of head and neck radiotherapy: Part 1 Aust Dent J. 2001;46:88–94
22. Mod D, Mod H, Jha AK. Oral and dental complications of head and neck radiotherapy and their management J Nepal Health Res Counc. 2013;11:300–4
23. Kanatas AN, Rogers SN, Martin MV. A practical guide for patients undergoing exodontia following radiotherapy to the oral cavity Dent Update. 2002;29:498–503
24. Peterson DE. Pretreatment strategies for infection prevention in chemotherapy patients NCI Monogr. 1990;9:61–71
25. Hong CH, Napeñas JJ, Hodgson BD, Stokman MA, Mathers-Stauffer V, Elting LS, et al A systematic review of dental disease in patients undergoing cancer therapy Support Care Cancer. 2010;18:1007–21
26. Marx RE. Osteoradionecrosis: A new concept of its pathophysiology J Oral Maxillofac Surg. 1983;41:283–8
27. Wong JK, Wood RE, McLean M. Conservative management of osteoradionecrosis Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1997;84:16–21
28. Annane D, Depondt J, Aubert P, Villart M, Géhanno P, Gajdos P, et al Hyperbaric oxygen therapy for radionecrosis of the jaw: A randomized, placebo-controlled, double-blind trial from the ORN96 study group J Clin Oncol. 2004;22:4893–900
29. Joshi VK. Dental treatment planning and management for the mouth cancer patient Oral Oncol. 2010;46:475–9
30. Muanza TM, Cotrim AP, McAuliffe M, Sowers AL, Baum BJ, Cook JA, et al Evaluation of radiation-induced oral mucositis by optical coherence tomography Clin Cancer Res. 2005;11:5121–7
31. Luo DH, Hong MH, Guo L, Cao KJ, Deng MQ, Mo HY, et al Analysis of oral mucositis risk factors during radiotherapy for nasopharyngeal carcinoma patients and establishment of a discriminant model Ai Zheng. 2005;24:850–4
32. Vissink A, Jansma J, Spijkervet FK, Burlage FR, Coppes RP. Oral sequelae of head and neck radiotherapy Crit Rev Oral Biol Med. 2003;14:199–212
33. Scully C, Sonis S, Diz PD. Oral mucositis Oral Dis. 2006;12:229–41
34. Lalla RV, Bowen J, Barasch A, Elting L, Epstein J, Keefe DM, et al MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy Cancer. 2014;120:1453–61
35. Kanuga S. Cryotherapy and keratinocyte growth factor may be beneficial in preventing oral mucositis in patients with cancer, and sucralfate is effective in reducing its severity J Am Dent Assoc. 2013;144:928–9
36. Praetorius NP, Mandal TK. Alternate delivery route for amifostine as a radio-/chemo-protecting agent J Pharm Pharmacol. 2008;60:809–15
37. Kaanders JH, Fleming TJ, Ang KK, Maor MH, Peters LJ. Devices valuable in head and neck radiotherapy Int J Radiat Oncol Biol Phys. 1992;23:639–45
38. Bensadoun RJ, Franquin JC, Ciais G, Darcourt V, Schubert MM, Viot M, et al Low-energy He/Ne laser in the prevention of radiation-induced mucositis.A multicenter phase III randomized study in patients with head and neck cancer Support Care Cancer. 1999;7:244–52
39. Barber C, Powell R, Ellis A, Hewett J. Comparing pain control and ability to eat and drink with standard therapy vs.gelclair: A preliminary, double centre, randomised controlled trial on patients with radiotherapy-induced oral mucositis Support Care Cancer. 2007;15:427–40
40. Hawley P, Hovan A, McGahan CE, Saunders D. A randomized placebo-controlled trial of manuka honey for radiation-induced oral mucositis Support Care Cancer. 2014;22:751–61
41. Huang EY, Leung SW, Wang CJ, Chen HC, Sun LM, Fang FM, et al Oral glutamine to alleviate radiation-induced oral mucositis: A pilot randomized trial Int J Radiat Oncol Biol Phys. 2000;46:535–9
42. Eldridge A, Fan M, Woloschak G, Grdina DJ, Chromy BA, Li JJ, et al Manganese superoxide dismutase interacts with a large scale of cellular and mitochondrial proteins in low-dose radiation-induced adaptive radioprotection Free Radic Biol Med. 2012;53:1838–47
43. LeVeque FG, Parzuchowski JB, Farinacci GC, Redding SW, Rodu B, Johnson JT, et al Clinical evaluation of MGI 209, an anesthetic, film-forming agent for relief from painful oral ulcers associated with chemotherapy J Clin Oncol. 1992;10:1963–8
44. Barker G, Loftus L, Cuddy P, Barker B. The effects of sucralfate suspension and diphenhydramine syrup plus kaolin-pectin on radiotherapy-induced mucositis Oral Surg Oral Med Oral Pathol. 1991;71:288–93
45. Davies AN, Singer J. A comparison of artificial saliva and pilocarpine in radiation-induced xerostomia J Laryngol Otol. 1994;108:663–5
46. Ferreira PR, Fleck JF, Diehl A, Barletta D, Braga-Filho A, Barletta A, et al Protective effect of alpha-tocopherol in head and neck cancer radiation-induced mucositis: A double-blind randomized trial Head Neck. 2004;26:313–21
47. Oshitani T, Okada K, Kushima T, Suematsu T, Obayashi K, Hirata Y, et al Clinical evaluation of sodium alginate on oral mucositis associated with radiotherapy Nihon Gan Chiryo Gakkai Shi. 1990;25:1129–37
    48. Roopashri G, Jayanthi K, Guruprasad R. Efficacy of benzydamine hydrochloride, chlorhexidine, and povidone iodine in the treatment of oral mucositis among patients undergoing radiotherapy in head and neck malignancies: A drug trail Contemp Clin Dent. 2011;2:8–12
      49. Berger A, Henderson M, Nadoolman W, Duffy V, Cooper D, Saberski L, et al Oral capsaicin provides temporary relief for oral mucositis pain secondary to chemotherapy/radiation therapy J Pain Symptom Manage. 1995;10:243–8
      50. Saunders DP, Epstein JB, Elad S, Allemano J, Bossi P, van de Wetering MD, et al Systematic review of antimicrobials, mucosal coating agents, anesthetics, and analgesics for the management of oral mucositis in cancer patients Support Care Cancer. 2013;21:3191–207
      51. Sonis ST, Lindquist L, Van Vugt A, Stewart AA, Stam K, Qu GY, et al Prevention of chemotherapy-induced ulcerative mucositis by transforming growth factor beta 3 Cancer Res. 1994;54:1135–8
      52. Mose S, Adamietz IA, Saran F, Thilmann C, Heyd R, Knecht R, et al Can prophylactic application of immunoglobulin decrease radiotherapy-induced oral mucositis? Am J Clin Oncol. 1997;20:407–11
      53. Leborgne JH, Leborgne F, Zubizarreta E, Ortega B, Mezzera J. Corticosteroids and radiation mucositis in head and neck cancer.A double-blind placebo-controlled randomized trial Radiother Oncol. 1998;47:145–8
      54. Scott RW, Tew GN. Mimics of host defense proteins; strategies for translation to therapeutic applications Curr Top Med Chem. 2017;17:576–89
      55. Schmidt M, Haagen J, Noack R, Siegemund A, Gabriel P, Dörr W, et al Effects of bone marrow or mesenchymal stem cell transplantation on oral mucositis (mouse) induced by fractionated irradiation Strahlenther Onkol. 2014;190:399–404
      56. Davies RM, Ellwood RP, Davies GM. The effectiveness of a toothpaste containing triclosan and polyvinyl-methyl ether maleic acid copolymer in improving plaque control and gingival health: A systematic review J Clin Periodontol. 2004;31:1029–33
      57. Gunsolley JC. A meta-analysis of six-month studies of antiplaque and antigingivitis agents J Am Dent Assoc. 2006;137:1649–57
      58. Blinkhorn A, Bartold PM, Cullinan MP, Madden TE, Marshall RI, Raphael SL, et al Is there a role for triclosan/copolymer toothpaste in the management of periodontal disease? Br Dent J. 2009;207:117–25
      59. Rogers SN, Ahad SA, Murphy AP. A structured review and theme analysis of papers published on 'quality of life' in head and neck cancer: 2000-2005 Oral Oncol. 2007;43:843–68
      60. Plemons JM, Al-Hashimi I, Marek CL; American Dental Association Council on Scientific Affairs. Managing xerostomia and salivary gland hypofunction: Executive summary of a report from the American Dental Association Council on Scientific Affairs J Am Dent Assoc. 2014;145:867–73
      61. Criswell MA, Sinha CK. Hyperthermic, supersaturated humidification in the treatment of xerostomia Laryngoscope. 2001;111:992–6
      62. Wolff A, Fox PC, Porter S, Konttinen YT. Established and novel approaches for the management of hyposalivation and xerostomia Curr Pharm Des. 2012;18:5515–21
      63. Jawad H, Hodson NA, Nixon PJ. A review of dental treatment of head and neck cancer patients, before, during and after radiotherapy: Part 1 Br Dent J. 2015;218:65–8
      64. Nelson GM. Biology of taste buds and the clinical problem of taste loss Anat Rec. 1998;253:70–8
      65. Lalla RV, Sonis ST, Peterson DE. Management of oral mucositis in patients who have cancer Dent Clin North Am. 2008;52:61–77, viii
      66. Pappas PG, Kauffman CA, Andes DR, Clancy CJ, Marr KA, Ostrosky-Zeichner L, et al Clinical practice guideline for the management of candidiasis: 2016 update by the infectious diseases society of America Clin Infect Dis. 2016;62:e1–50
      67. Lalla RV, Latortue MC, Hong CH, Ariyawardana A, D'Amato-Palumbo S, Fischer DJ, et al A systematic review of oral fungal infections in patients receiving cancer therapy Support Care Cancer. 2010;18:985–92
      68. Nicolatou-Galitis O, Velegraki A, Sotiropoulou-Lontou A, Dardoufas K, Kouloulias V, Kyprianou K, et al Effect of fluconazole antifungal prophylaxis on oral mucositis in head and neck cancer patients receiving radiotherapy Support Care Cancer. 2006;14:44–51
      69. Glenny AM, Fernandez Mauleffinch LM, Pavitt S, Walsh T. Interventions for the prevention and treatment of herpes simplex virus in patients being treated for cancer? Cochrane Database Syst Rev ;CD. 6;: Interventions for the prevention and treatment of herpes simplex virus in patients being treated for cancer Cochrane Database Syst Rev 2009;CD006706 doi: 101002/14651858CD006706
        70. Chilukuri S, Rosen T. Management of acyclovir-resistant herpes simplex virus Dermatol Clin. 2003;21:311–20
        71. Bhandarkar SS, MacKelfresh J, Fried L, Arbiser JL. Targeted therapy of oral hairy leukoplakia with gentian violet J Am Acad Dermatol. 2008;58:711–2
        72. Moura MD, Haddad JP, Senna MI, Ferreira e Ferreira E, Mesquita RA. A new topical treatment protocol for oral hairy leukoplakia Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2010;110:611–7
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          Keywords:

          Head and neck cancer; oral mucositis; osteoradionecrosis; xerostomia

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