Dentistry and Medical Research

REVIEW ARTICLE
Year
: 2020  |  Volume : 8  |  Issue : 1  |  Page : 10--17

Public health significance of head and neck cancer – A narrative review


Fatma Ahmed1, Sabria Al Marshoudi2, Syed Wali Peeran3,  
1 Department of Public Health and Epidemiology, University of Miami, Miami, FL, USA
2 Department of Malaria and Vectors Born Disease, Directorate of Disease Surveillance and Control, MOH, Oman
3 Department of Periodontics, Faculty of Dentistry, Sebha University, Faculty of Dentistry, Sebha University, Sebha, Libya

Correspondence Address:
Fatma Ahmed
Department of Public Health and Epidemiology, University of Miami, Miami, FL
USA

Abstract

Head and neck cancers (HNCs) are a term describing the biologically heterogeneous group of cancers that affect the upper aerodigestive tract and share a common anatomic origin. HNC is one of the most prevalent types of cancers globally. This narrative review is based on a comprehensive search of Medline, Google Scholar, the Cochrane Database of Systematic Reviews, and other electronic databases. The scientific literature in English language dealing with HNCs with relevance to public health significance was reviewed. Various topics of controversy in dealing with the public health significance of HNC have been highlighted in this report in context to the needs of the HNC patients. The search revealed significant gaps in public health delivery for HNC patients. Moreover, conclusively, we recommend that the health-care professionals should be better trained to handle the needs of HNC patients.



How to cite this article:
Ahmed F, Marshoudi SA, Peeran SW. Public health significance of head and neck cancer – A narrative review.Dent Med Res 2020;8:10-17


How to cite this URL:
Ahmed F, Marshoudi SA, Peeran SW. Public health significance of head and neck cancer – A narrative review. Dent Med Res [serial online] 2020 [cited 2020 Aug 3 ];8:10-17
Available from: http://www.dmrjournal.org/text.asp?2020/8/1/10/285212


Full Text



 Introduction



Head and neck cancers (HNCs) are a term describing the biologically heterogeneous group of cancers that affect the upper aerodigestive tract and share a common anatomic origin.[1],[2],[3] HNCs include those that affect the lips, oral cavity, pharynx, larynx, paranasal sinuses, and salivary glands.[4]

 Incidence and Prevalence



HNC comprise up to 3% of all cancers in the United States with an estimated 63,000 people affected and 13,000 deaths in 2017.[5],[6] They are the seventh most common cancers globally, accounting for over 500,000 new cases annually and affect males more than females.[1],[7],[8],[9] HNCs are described based on the cell type they start with. Most of the HNCs are squamous cell carcinomas[10] HNC is believed to be a preventable disease caused by the exposure of epithelium to carcinogens such as tobacco and alcohol or human papillomavirus (HPV), the common sexually transmitted infection.[1],[10],[11],[12],[13],[14],[15],[16],[17] Further, in South Asia, an innocuously appearing nut, betel nut, which is habitually chewed in some communities is one of the leading causes of oral cancers.[18],[19],[20] Recent studies suggest a simultaneous decline in tobacco-associated carcinomas and an increase in HPV-mediated carcinomas, especially among younger males.[3],[21],[22],[23],[24]

 Cost of Healthcare in Head and Neck Cancer Patients



HNCs may affect various aspects of human life. They result in a direct cost due to screening, diagnosis radiotherapy (RT), chemotherapy, surgery, long-term supportive care, and follow-up care as well as indirect costs such as reduced workforce participation, early death, and the resultant loss of productivity.[25],[26] Thus, costs of HNC for individual patients are substantial and the cumulative public health burden is colossal.[27] Mariotto et al. estimated that the surviving cancer patients in the US to be 18.1 million cancer and the associated costs of cancer care to be 157.77 billion US dollars in 2020 for US.[28] It was estimated that 3.6 billion was spent on HNC care in the US in 2014.[29],[30] The initial HNC treatment costs for an individual patient are 41,980 and 39,179 USD among females and males, respectively. Further, the continuing annual costs per HNC patient, female and males were 4826 USD and 4001 USD, respectively.[28],[31] In another study which used commercial and Medicare Data, a 6-month adjusted cost was 60,414 USD for metastatic HNC and 21,141 USD for recurrent disease in 2008.[32] Further, studies in developed European countries showed similar costs of HNC. In a study in Germany, they found 4,898 inpatient rehabilitations for HNC patients in 2008 and cost including direct as well as the indirect cost was €365.78 million.[33]

 Mortality



HNC patients are characterized by high levels of comorbidity, increased risk of psychosocial distress, and an exposure to highly toxic treatment strategies.[34] Hence, deaths in HNC patients can be due to cancer as well as noncancer causes. The noncancer causes that predispose HNC patients to death include advanced age and comorbid cardiopulmonary diseases.[35],[36] Mortality in HNC patients can also be due to treatment-related mortality such as sepsis, organ failure, pulmonary embolism, aspiration pneumonia, surgical complications, or vascular disease.[35],[36],[37] Due to the above-mentioned reasons, the death among the HNC patients can be rapid and unpredictable.[38] The past decades have witnessed a steady decline in the US of HNC mortality, despite a stable incidence.[36],[39],[40],[41] In addition, the incidence of HNC in African Americans has reduced considerably over the past two decades and is now lower than that in whites. The mortality rate has also seen a downtrend among African Americans, but it remains higher than that in whites.[39] Among the HNC, squamous cell carcinomas are the most common ones in incidence as well as in mortality.[38],[42] Patients with recurrent and metastatic HNC have poorer survival rates, a median overall survival for patients with recurrent and/or metastatic squamous cell HNC remains <1 year despite available advancements in treatment.[43]

 Quality of Life in Head and Neck Cancer Patients



Quality of life (QoL) is reflective of the patient's point of view about his/her general well-being. It is a subjective, multidimensional concept that includes physical, occupational, social functional, and psychological well-being. It encompasses within it both positive and negative features of life.[44],[45],[46] The World Health Organization defines QoL as an “individual's perception of their position in life in the context of the culture and value systems in which they live and in relation to their goals, expectations, standards and concerns.”[47],[48],[49] It is of paramount consideration in the management of HNC.[50] The head and neck region is an anatomically complex and functionally significant region. HNC patients encounter various challenges prior and post HNC treatment, including dysphagia, pain, xerostomia, dietary restrictions, physical restrictions, and psychological stress besides facial disfigurement and problems in sexual life.[45],[46] HNC problems can cause profound long-term adverse effects on the QoL of a patient for many years even after treatment. QoL in HNC patients is affected by different factors, such as patient's age, occupation, performance, status, comorbid medical conditions, compliance, pathology, and its extension and advance, timing of presentation, availability of experienced specialists in the required fields, relative impact of the treatment options such as extensive surgical resection, neck dissection, and postoperative radiation.[50],[51] The major problem experienced by the HNC patients is pain. It requires high levels of attention by the clinicians to improve their QoL.[51] Studies have shown varying results with QoL in HNC patients with some finding no improvement in the QoL in HNC patients despite intervention.[46] In a prospective study, Mehanna and Morton found that at 10 years following diagnosis, overall QoL (life satisfaction), decreased significantly in HNC patients.[52] The Institute of Medicine in 2001 constituted a report titled Crossing the Quality Chasm: A New Health System for the 21st Century reporting on a national initiative to improve the quality of care and consequently QoL in the US. The aims articulated in the report emphasized increasing safety and avoiding injuries to the HNC patients, delivering services based on scientific knowledge, to deliver treatment which is individualized and tailor-made for patients, timely delivery of patient care, increasing efficiency, and avoiding wastage of care delivery. The report also articulated placing emphasis on equitable delivery of care which is devoid of variance of health-care delivery based on personal characteristics, patient gender, ethnicity, geography, and socioeconomic status.[53],[54]

 Treatment Kinds



The primary options available for HNC treatment are surgery, radiation therapy, systemic therapy including chemotherapy and molecularly targeted agents; the targeted therapy.[10],[55] The selection of treatment options in HNC treatment largely depends on the stage, location, and severity of the neoplasm along with the general health consideration of the patient.[56] A single-modality treatment is generally sufficient to manage the HNC in the early stages, whereas a multidisciplinary approach is necessary in HNC with advanced stages of the neoplasm.[8]

Surgery remains the first and foremost option for the treatment of in early-stage HNC patients. The neoplasm in such patients can be treated with surgery without functional impairment.[8] In cases with oral cancer, it remains the mainstay of therapy even in advanced stages of the disease.[17] Some of the various surgical procedures that are undertaken in the treatment of HNC are partial glossectomy, “commando” procedure, transoral laser surgery, various types of neck dissections including selective neck dissection, modified radical neck dissection, radical neck dissection, extended radical neck dissection, and reconstructive surgery.[17],[57] The side effects of the surgery depend on the location and type of surgery carried over and may include difficulty in chewing, swallowing, speaking, damage to the adjacent nerves, and facial disfigurement.[58]

RT is the use of high-energy radiation to destroy cancer cells by causing DNA damage at a cellular level or by an indirect effect of free radical formation.[57],[59] It remains a viable tool in treatment of HNC.[60] However, advances in surgical techniques and reconstructive options have led to a decrease in the use of RT.[57] RT for HNC patients can be classified into external irradiation and brachytherapy.[61] External beam radiation therapy with or without concomitant brachytherapy is used in HNC patients as an alternative to surgery.[17] Hyperfractionated RT with platinum-based chemotherapy (PC) is used in the treatment of recurrent squamous cell HNC.[8] Moreover, RT is also used as palliative therapy for treating symptomatic metastatic sites.[62] RT often follows with side effects including reversible ones such as mucositis and dysgeusia (taste loss) and the irreversible lifelong challenges with hyposalivation, xerostomia, radiation-related caries (RRC), progressive periodontal loss, soft-tissue necrosis, and osteoradionecrosis (ORN).[63],[64],[65] These side effects of RT are dose-related and have an immense detrimental effect on the QoL of the HNC patients.[65],[66]

Chemotherapy employs drugs and it destroys all rapidly dividing cells such as the cancer cells, usually by stopping their ability to grow and divide.[67],[68] Conventionally, it has been used in HNC therapy. PC with either cisplatin or carboplatin is used as the first-line treatment in cases of inoperable recurrent or metastatic HNC. In cases of squamous cell HNC, PC along with 5-fluorouracil and cetuximab has been shown to result in increased overall median survival.[62],[69],[70],[71]

Targeted therapy is similar to conventional chemotherapy. However, the pharmacological agents in the case of targeted therapy are designed to specifically inhibit cancer cell growth, increase their death, and restrict their spread without harming normal cells.[67],[68] Cetuximab (Erbitux) is an IgG1 monoclonal antibody. It binds to a protein on the surface of the cancer cells, inhibits the epidermal growth factor receptor and thus stops them growing and dividing. Hence, it is used a target therapy to treat the colorectal cancer and HNCs. It is generally administered in conjunction with RT.[67],[68],[72]

The tumor cells prevent detection and elimination by the suppression of the host immune system. Immune checkpoint inhibitors (ICIs), a recent addition in cancer therapeutics, interrupt the immunosuppressive pathways called inhibitory checkpoints used by cancer cells.[73] This immunotherapy has evolved as an attractive treatment option for recurrent and metastatic HNC with encouraging preliminary data from studies involving ICIs (e.g., pembrolizumab and nivolumab) and toll-like receptor agonists (e.g., motolimod).[43] Asymptomatic HNC patients with a low disease burden, are often treated with single-agent regimens to keep the side effects of therapy at the minimum. In case of recurrent and metastatic squamous cell HNC commonly used drugs for treatment include docetaxel, paclitaxel, cetuximab, capecitabine, pemetrexed, and methotrexate.[62]

Photodynamic therapy (PDT) is a newly emerging, minimally invasive therapeutic modality which is clinically approved for cancer therapy.[74],[75] PDT is based on the principle that light has the ability to interact with certain substances called photosensitizers which are light activatable to produce cytotoxic species. When a photosensitizer absorbs light energy of a specific wavelength, in the presence of light, photochemical reactions take place. The end products of these reactions, singlet oxygen and other reactive oxygen species, directly damage biomolecules, and subcellular organelles and consequently produce cell death. Thus, PDT a two-stage procedure, that starts with administration of photosensitizer followed by a locally directed light exposure, is employed for confined tumor destruction.[74] In addition, because of cancer, the QoL will be affected either directly or indirectly and as a result there will be oral health needs and care is required.

 Oral Health-related Complications of Head and Neck Cancer Patients



Salivary gland function

Saliva in the oral cavity serves the important role of maintaining the oral and general homeostasis.[76] Radiation induces damage to the salivary glands diminishes both amount of salivary output as well as affects its quality.[77] This, salivary hypofunction predisposes HNC patients to oral discomfort or pain, difficulty in speaking, chewing, or swallowing, xerostomia, and retrograde infection of the salivary glands.[76],[78],[79]

Radiation-related caries

RRC is an aggressive and clinically seen side effect of RT.[80] RRC development is suggested to be an indirect effect of radiation-induced salivary gland damage.[79],[81] As damage to salivary glands with concomitant hyposalivation and alteration to the chemical composition of saliva are common irreversible side-effect of RT in HNC.[63],[64],[82] An alteration in the oral microbiota with an increase in the number of cariogenic bacteria following RT is also noticed.[64] Moreover, the tooth substrate is also affected by the direct exposure of radiation, altering and compromising the structural and mechanical properties of enamel, coronal dentin as well as root dentin.[83],[84],[85] Further, the intake of soft and carbohydrate-rich diet along with poor oral hygiene could contribute to the progress of this atypical caries.[80] RRC is generally encountered clinically in the cervical and incisal area of the tooth. The pattern of RRC appears as a “cervical ring” and hence does not appear like caries in patients who have not been exposed to radiation.[63],[80] This characteristic appearance of involving more than one surface gives it the name “caries circularis.”[86] As radiation-related caries remains a lifelong, irreversible threat, robust programs should be put in place for its prevention.[87] A recent review by Hong et al. stated that cancer patients, post-RT had the highest DMFT (Decayed Missing and Filled teeth) compared to those post-chemotherapy and healthy controls.[88],[89] The review also showed that the use of fluoride products and chlorhexidine rinses was of benefit.[88]

Disfigurement due to head and neck cancer

HNC involves the most visible and recognizable parts of a human being.[90] HNC patients at times face extensive treatment protocols including surgery with excision of the affected tissue.[91] Thereby, HNC patients could suffer facial disfigurement and experience substantial psychological trauma. Further, partners of HNC patients can be psychologically distressed. It can also have an impact on partners.[92],[93],[94],[95],[96],[97] Reconstructive surgery to improve the QoL of HNC patients along with patient counseling to overcome anxieties and calm emotional reactions and partner and public education are necessary.[91],[98],[99],[100]

Osteoradionecrosis

ORN of the jaws is an infrequent complication.[101] It is avascular, aseptic necrosis of the jaws caused as a late complication of RT for HNC.[102],[103] ORN is characterized by bone tissue necrosis, decreased bone density with fractures, destruction of bony cortex, and loss of spongiosa trabeculations in spongy bone and failure to bone healing.[104],[105] It is seen in HNC patients who receive more than 6000 cGy (centigrays) of ionizing radiation even decades after treatment.[106] ORN increases in incidence in HNC patients who are tobacco smokers or use bisphosphonates.[107] Moreover, ORN affects mandible more than maxilla as mandible has dense bone and is poorly vascularized when compared to maxilla.[64] Dental trauma such as extractions, periodontal disease, denture induce trauma can trigger ORN in post-RT patients.[108],[109] Hence, extractions are to be carried over in HNC patients prior to RT.[110],[111]

Trimus

Trismus is characterized by restricted mouth opening due to a decrease in the range of motion of the mastication muscles.[77],[112] Surgery or RT involving the muscles of mastication and temporomandibular joints can cause trismus and can adversely affect QoL in HNC patients.[64],[113],[114],[115] It is a common late-term side-effect of RT.[115]

 Oral Health Care Guidelines for Head and Neck Cancer Patients



Given the above factors that affect the oral health care of the patients as a result of HNC and the treatment complications, it is necessary to provide suitable oral health care that will help the patients to avoid the complications. HNC is a complicated disease. The oral health needs of HNC are wide ranging which include early detection of oral malignancy, treatment of the oral complications of HNC and its treatment and maintenance of oral hygiene and plaque control in HNC.[116],[117]

Plaque control

Dental plaque is the primary cause of the most common dental ailments, dental caries and periodontal disease and also contributes to HNC risk.[118],[119] Diagnosis and treatment of HNC has a severe negative impact on psychosocial functioning of the patients and causes a relatively high rate of depression among HNC patients.[120],[121],[122] HNC and its treatment can also lead to mutilation of oral tissues. Thus, rendering oral hygiene maintenance and plaque control an uphill task. Therefore, plaque control and oral hygiene maintenance in HNC patients are of significance.[64]

Guidelines for oral health care in head and neck cancer patients

The guidelines for oral hygiene and health care among HNC cancer patients provided by the National Institute of Dental and Craniofacial Research include several recommendations.[123] First, the guidelines include regular use of a soft toothbrush after every meal and before going to sleep, as well as regular but careful use of dental floss while avoiding hurting the periodontal tissues. Another recommendation is the use of alcohol-free mouth rinse and fluoride gels. The guidelines also include avoidance of alcohol, tobacco products, spicy food, and sweetened drinks. Finally, jaw exercise could be of help in patients with jaw stiffness following radiation.[123] Assessing and promoting knowledge of these guidelines among HNC patients can be an important part of health promotion.

 Factors That May Promote or Act as Barrier to Oral Health Care among Head and Neck Cancer Patients



However, some factors may promote or act as barriers to oral health care among HNC patients such as the need/availability of access to dental care and dental literacy among HNC patients.

Access to dental care

Access to oral health care is important for HNC patients.[124] Many HNC patients can have poor oral hygiene even before the diagnosis of HNC. The disease can compound the poor oral hygiene status, with depression of patient and with the mutilation of oral tissues both by disease as well as treatment. Yet, the number of HNC patients surviving the disease and living longer has also increased with advancements in treatment.[124],[125] This requires attention to be given to oral health care. Dental health professionals with sound knowledge to address HNC patients' needs should be part of the team of professionals that provide cancer care.[124],[125] Dental health-care providers should be at the cancer center, nearby hospital dental programs or in community.[125]

Dental health literacy

An adequate and accurate knowledge of the dental caries, periodontal disease among HNC patients their burden, as well as the oral complications due to HNC and its treatment, is necessary part of the dental literacy of the HNC patients. The dental health-care provider should provide oral hygiene instructions regarding brushing and flossing. Oral hygiene practices should be taught and reinforced both before and after cancer therapy is imparted.[126] Dental education and treatment of dental ailments prior to cancer therapy can minimize some oral complications of cancer treatments.[127]

Further, it is also important that dental professionals are aware of and understand the methods for care of HNC patients.[127] They must possess a thorough knowledge of prevention and treatment of complications that arise from cancer therapy.[125] Studies have shown that many dental health professionals have inconsistent knowledge.[128],[129],[130],[131],[132],[133],[134],[135],[136] Hence, there is also a need to improve the knowledge and impart the required skills among the dental professionals to serve HNC patients.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1Rettig EM, D'Souza G. Epidemiology of head and neck cancer. Surg Oncol Clin N Am 2015;24:379-96.
2Parkin DM. Tobacco-attributable cancer burden in the UK in 2010. Br J Cancer 2011;105 Suppl 2:S6-13.
3Sturgis EM, Cinciripini PM. Trends in head and neck cancer incidence in relation to smoking prevalence: An emerging epidemic of human papillomavirus-associated cancers? Cancer 2007;110:1429-35.
4Menzin J, Lines LM, Manning LN. The economics of squamous cell carcinoma of the head and neck. Curr Opin Otolaryngol Head Neck Surg 2007;15:68-73.
5Siegel RL, Miller KD, Jemal A. Cancer statistics, 2017. CA Cancer J Clin 2017;67:7-30.
6Daraei P, Moore CE. Racial disparity among the head and neck cancer population. J Cancer Educ 2015;30:546-51.
7Morinière S. Epidemiology of head and neck cancer. Rev Prat 2006;56:1637-41.
8Denaro N, Russi EG, Adamo V, Merlano MC. State-of-the-art and emerging treatment options in the management of head and neck cancer: News from 2013. Oncology 2014;86:212-29.
9Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin 2013;63:11-30.
10Argiris A, Karamouzis MV, Raben D, Ferris RL. Head and neck cancer. Lancet 2008;371:1695-709.
11Warnakulasuriya S. Causes of oral cancer-An appraisal of controversies. Br Dent J 2009;207:471-5.
12Lee LA, Huang CG, Tsao KC, Liao CT, Kang CJ, Chang KP, et al. Increasing rates of low-risk human papillomavirus infections in patients with oral cavity squamous cell carcinoma: Association with clinical outcomes. J Clin Virol 2013;57:331-7.
13Kreimer AR, Johansson M, Waterboer T, Kaaks R, Chang-Claude J, Drogen D, et al. Evaluation of human papillomavirus antibodies and risk of subsequent head and neck cancer. J Clin Oncol 2013;31:2708-15.
14Chaturvedi AK. Epidemiology and clinical aspects of HPV in head and neck cancers. Head Neck Pathol 2012;6 Suppl 1:S16-24.
15D'Souza G, Kreimer AR, Viscidi R, Pawlita M, Fakhry C, Koch WM, et al. Case–control study of human papillomavirus and oropharyngeal cancer. N Engl J Med 2007;356:1944-56.
16Tabrizi SN, Brotherton JML, Kaldor JM, Skinner SR, Cummins E, Liu B, et al. Fall in human papillomavirus prevalence following a national vaccination program. J Infect Dis 2012;206:1645-51.
17Day TA, Davis BK, Gillespie MB, Joe JK, Kibbey M, Martin-Harris B, et al. Oral cancer treatment. Curr Treat Options Oncol 2003;4:27-41.
18Doyle K. Asia's deadly secret: The scourge of the betel nut-BBC News. BBC News; 22 March, 2015. Available from: http://www.bbc.com/news/health-31921207. [Last accessed on 2017 Jun 08].
19Sharan RN, Mehrotra R, Choudhury Y, Asotra K. Association of betel nut with carcinogenesis: Revisit with a clinical perspective. PLoS One 2012;7:e42759.
20Hernandez BY, Zhu X, Goodman MT, Gatewood R, Mendiola P, Quinata K, et al. Betel nut chewing, oral premalignant lesions, and the oral microbiome. PLoS One 2017;12:e0172196.
21Mifsud M, Eskander A, Irish J, Gullane P, Gilbert R, Brown D, et al. Evolving trends in head and neck cancer epidemiology: Ontario, Canada 1993-2010. Head Neck 2017;39:1770-8.
22Hocking JS, Stein A, Conway EL, Regan D, Grulich A, Law M, et al. Head and neck cancer in Australia between 1982 and 2005 show increasing incidence of potentially HPV-associated oropharyngeal cancers. Br J Cancer 2011;104:886-91.
23Westra WH. The changing face of head and neck cancer in the 21st century: The impact of HPV on the epidemiology and pathology of oral cancer. Head Neck Pathol 2009;3:78-81.
24Chaturvedi AK, Engels EA, Pfeiffer RM, Hernandez BY, Xiao W, Kim E, et al. Human papillomavirus and rising oropharyngeal cancer incidence in the United States. J Clin Oncol 2011;29:4294-301.
25Wissinger E, Griebsch I, Lungershausen J, Foster T, Pashos CL. The economic burden of head and neck cancer: A systematic literature review. Pharmacoeconomics 2014;32:865-82.
26Bradley CJ, Yabroff KR, Dahman B, Feuer EJ, Mariotto A, Brown ML. Productivity costs of cancer mortality in the United States: 2000-2020. J Natl Cancer Inst 2008;100:1763-70.
27Lang K, Menzin J, Earle CC, Jacobson J, Hsu MA. The economic cost of squamous cell cancer of the head and neck: Findings from linked SEER-Medicare data. Arch Otolaryngol Head Neck Surg 2004;130:1269-75.
28Mariotto AB, Yabroff KR, Shao Y, Feuer EJ, Brown ML. Projections of the cost of cancer care in the United States: 2010-2020. J Natl Cancer Inst 2011;103:117-28.
29Graph by Cancer Site and Phase of Care. Cancer Prevalence and Cost of Care Projections. Available from: https://costprojections.cancer.gov/graph.php. [Last accessed on 2017 Jun 08].
30A Snapshot of Head and Neck Cancer. National Cancer Institute. Available from: https://www.cancer.gov/research/progress/snapshots/head-and-neck. [Last accessed on 2017 Jun 08].
31Annual Costs of Cancer Care. Cancer Prevalence and Cost of Care Projections. National Cancer Institute. Available from: https://costprojections.cancer.gov/annual.costs.html. [Last accessed on 2017 Jun 07].
32Kim Le T, Winfree KB, Yang H, Marynchenko M, Yu AP, Frois C, et al. Treatment patterns and economic burden of metastatic and recurrent locally-advanced head and neck cancer patients. J Med Econ 2012;15:786-95.
33Klussmann JP, Schädlich PK, Chen X, Rémy V. Annual cost of hospitalization, inpatient rehabilitation, and sick leave for head and neck cancers in Germany. Clinicoecon Outcomes Res 2013;5:203-13.
34Ringash J. Facing head and neck cancer deaths head on: Lessons for survival. Cancer 2014;120:1446-9.
35Argiris A, Brockstein BE, Haraf DJ, Stenson KM, Mittal BB, Kies MS, et al. Competing causes of death and second primary tumors in patients with locoregionally advanced head and neck cancer treated with chemoradiotherapy. Clin Cancer Res 2004;10:1956-62.
36Mell LK, Dignam JJ, Salama JK, Cohen EE, Polite BN, Dandekar V, et al. Predictors of competing mortality in advanced head and neck cancer. J Clin Oncol 2010;28:15-20.
37Madan R, Kairo AK, Sharma A, Roy S, Singh S, Singh L, et al. Aspiration pneumonia related deaths in head and neck cancer patients: A retrospective analysis of risk factors from a tertiary care centre in North India. J Laryngol Otol 2015;129:710-4.
38Fullarton M, Pybus S, Mayland C, Rogers SN. Analysis of deaths between 2007 and 2012 of patients with cancer of the head and neck on a surgical ward at a regional centre and in an independent hospice. Br J Oral Maxillofac Surg 2016;54:62-7.
39A Snapshot of Head and Neck Cancer. National Cancer Institute. Available from: https://www.cancer.gov/research/progress/snapshots/head-and-neck. [Last accessed on 2017 Jun 15].
40Available from: http://planning.cancer.gov/disease/Head_and_Neck-Snapshot.pdf. [Last accessed on 2017 Jun 15].
41Pulte D, Brenner H. Changes in survival in head and neck cancers in the late 20th and early 21st century: A period analysis. Oncologist 2010;15:994-1001.
42Sanderson RJ, Ironside JA. Squamous cell carcinomas of the head and neck. BMJ 2002;325:822-7.
43Jacob LA, Chaudhuri T, Lakshmaiah KC, Babu KG, Dasappa L, Babu M, et al. Current status of systemic therapy for recurrent and/or metastatic squamous cell carcinoma of the head and neck. Indian J Cancer 2016;53:471-7.
44School IB. Quality of Life: Everyone Wants It, But What Is It? Forbes; 4 September, 2013. Available fom: https://www.forbes.com/sites/iese/2013/09/04/quality-of-life-everyone-wants-it-but-what-is-it/. [Last accessed on 2017 Jun 19].
45Murphy BA, Ridner S, Wells N, Dietrich M. Quality of life research in head and neck cancer: A review of the current state of the science. Crit Rev Oncol Hematol 2007;62:251-67.
46Majid A, Sayeed BZ, Khan M, Lakhani M, Saleem MM, Rajani H, et al. Assessment and improvement of quality of life in patients undergoing treatment for head and neck cancer. Cureus 2017;9:e1215.
47Saxena S, Orley J; WHOQOL Group. Quality of life assessment: The world health organization perspective. Eur Psychiatry 1997;12 Suppl 3:263s-6s.
48WHO. WHOQOL: Measuring Quality of Life; March, 2014. Available from: http://www.who.int/healthinfo/survey/whoqol-qualityoflife/en/. [Last accessed on 2017 Jul 21].
49Rogers SN, Semple C, Babb M, Humphris G. Quality of life considerations in head and neck cancer: United Kingdom National Multidisciplinary Guidelines. J Laryngol Otol 2016;130:S49-52.
50Rathod S, Livergant J, Klein J, Witterick I, Ringash J. A systematic review of quality of life in head and neck cancer treated with surgery with or without adjuvant treatment. Oral Oncol 2015;51:888-900.
51Onakoya PA, Nwaorgu OG, Adenipekun AO, Aluko AA, Ibekwe TS. Quality of life in patients with head and neck cancers. J Natl Med Assoc 2006;98:765-70.
52Mehanna HM, Morton RP. Deterioration in quality-of-life of late (10-year) survivors of head and neck cancer. Clin Otolaryngol 2006;31:204-11.
53Institute of Medicine (US) Committee on Quality of Health Care in America. Crossing the Quality Chasm: A New Health System for the 21st Century. Washington (DC): National Academies Press (US); 2014.
54Weber RS. Improving the quality of head and neck cancer care. Arch Otolaryngol Head Neck Surg 2007;133:1188-92.
55Treatment Options. Head and Neck Cancer. Available from: https://head-neck-cancer.canceraustralia.gov.au/treatment. [Last accessed on 2017 Jun 22].
56Head and Neck Cancer. Available from: https://www.cancer.gov/types/head-and-neck/head-neck-fact-sheet. [Last accessed on 2017 Jun 22].
57Watkinson J, Gilbert RW. Stell and Maran's Textbook of Head and Neck Surgery and Oncology. 5th ed. UK: CRC Press; 2011.
58Treatment Options. Head and Neck Cancer. Available from: https://head-neck-cancer.canceraustralia.gov.au. [Last accessed on 2017 Jun 23].
59Head and Neck Cancer: Treatment Options; 25 June, 2012. Available from: http://www.cancer.net/cancer-types/head-and-neck-cancer/treatment-options. [Last accessed on 2017 Jun 23].
60Jham BC, da Silva Freire AR. Oral complications of radiotherapy in the head and neck. Braz J Otorhinolaryngol 2006;72:704-8.
61Matsuzaki H, Tanaka-Matsuzaki K, Miyazaki F, Aoyama H, Ihara H, Katayama N, et al. The role of dentistry other than oral care in patients undergoing radiotherapy for head and neck cancer. Jpn Dent Sci Rev 2017;53:46-52.
62Price KA, Cohen EE. Current treatment options for metastatic head and neck cancer. Curr Treat Options Oncol 2012;13:35-46.
63Kielbassa AM, Hinkelbein W, Hellwig E, Meyer-Lückel H. Radiation-related damage to dentition. Lancet Oncol 2006;7:326-35.
64Tolentino Ede S, Centurion BS, Ferreira LH, Souza AP, Damante JH, Rubira-Bullen IR. Oral adverse effects of head and neck radiotherapy: Literature review and suggestion of a clinical oral care guideline for irradiated patients. J Appl Oral Sci 2011;19:448-54.
65van der Molen L, Heemsbergen WD, de Jong R, van Rossum MA, Smeele LE, Rasch CR, et al. Dysphagia and trismus after concomitant chemo-Intensity-Modulated Radiation Therapy (chemo-IMRT) in advanced head and neck cancer; dose-effect relationships for swallowing and mastication structures. Radiother Oncol 2013;106:364-9.
66Vissink A, Burlage FR, Spijkervet FK, Jansma J, Coppes RP. Prevention and treatment of the consequences of head and neck radiotherapy. Crit Rev Oral Biol Med 2003;14:213-25.
67Treatment Options. Head and Neck Cancer. Available from: https://head-neck-cancer.canceraustralia.gov.au/treatment. [Last accessed on 2017 Jun 24].
68Baudino TA. Targeted cancer therapy: The next generation of cancer treatment. Curr Drug Discov Technol 2015;12:3-20.
69Vermorken JB, Mesia R, Rivera F, Remenar E, Kawecki A, Rottey S, et al. Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med 2008;359:1116-27.
70de Mello RA, Gerós S, Alves MP, Moreira F, Avezedo I, Dinis J. Cetuximab plus platinum-based chemotherapy in head and neck squamous cell carcinoma: A retrospective study in a single comprehensive European cancer institution. PLoS One 2014;9:e86697.
71Guo Y, Shi M, Yang A, Feng J, Zhu X, Choi YJ, et al. Platinum-based chemotherapy plus cetuximab first-line for Asian patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck: Results of an open-label, single-arm, multicenter trial. Head Neck 2015;37:1081-7.
72Kimura H, Sakai K, Arao T, Shimoyama T, Tamura T, Nishio K. Antibody-dependent cellular cytotoxicity of cetuximab against tumor cells with wild-type or mutant epidermal growth factor receptor. Cancer Sci 2007;98:1275-80.
73Argiris A, Harrington KJ, Tahara M, Schulten J, Chomette P, Ferreira Castro A, et al. Evidence-based treatment options in recurrent and/or metastatic squamous cell carcinoma of the head and neck. Front Oncol 2017;7:72.
74van Straten D, Mashayekhi V, de Bruijn HS, Oliveira S, Robinson DJ. Oncologic Photodynamic Therapy: Basic Principles, Current Clinical Status and Future Directions. Cancers (Basel) 2017;9:19. Published 2017 Feb 18. doi:10.3390/cancers9020019.
75Benov L. Photodynamic therapy: Current status and future directions. Med Princ Pract 2015;24 Suppl 1:14-28.
76Saleh J, Figueiredo MA, Cherubini K, Salum FG. Salivary hypofunction: An update on aetiology, diagnosis and therapeutics. Arch Oral Biol 2015;60:242-55.
77Buglione M, Cavagnini R, Di Rosario F, Maddalo M, Vassalli L, Grisanti S, et al. Oral toxicity management in head and neck cancer patients treated with chemotherapy and radiation: Xerostomia and trismus (Part 2). Literature review and consensus statement. Crit Rev Oncol Hematol 2016;102:47-54.
78Mirabile A, Numico G, Russi EG, Bossi P, Crippa F, Bacigalupo A, et al. Sepsis in head and neck cancer patients treated with chemotherapy and radiation: Literature review and consensus. Crit Rev Oncol Hematol 2015;95:191-213.
79Vissink 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.
80Lieshout HF, Bots CP. The effect of radiotherapy on dental hard tissue — A systematic review. Clin Oral Investig 2014;18:17-24.
81Silva AR, Alves FA, Berger SB, Giannini M, Goes MF, Lopes MA. Radiation-related caries and early restoration failure in head and neck cancer patients. A polarized light microscopy and scanning electron microscopy study. Support Care Cancer 2010;18:83-7.
82Deng J, Jackson L, Epstein JB, Migliorati CA, Murphy BA. Dental demineralization and caries in patients with head and neck cancer. Oral Oncol 2015;51:824-31.
83Qing P, Huang S, Gao S, Qian L, Yu H. Effect of gamma irradiation on the wear behaviour of human tooth enamel. Sci Rep 2015;5:11568.
84Qing P, Huang S, Gao S, Qian L, Yu H. Effect of gamma irradiation on the wear behavior of human tooth dentin. Clin Oral Investig 2016;20:2379-86.
85Soares CJ, Castro CG, Neiva NA, Soares PV, Santos-Filho PC, Naves LZ, et al. Effect of gamma irradiation on ultimate tensile strength of enamel and dentin. J Dent Res 2010;89:159-64.
86Dobroś K, Hajto-Bryk J, Wróblewska M, Zarzecka J. Radiation-induced caries as the late effect of radiation therapy in the head and neck region. Contemp Oncol (Pozn) 2016;20:287-90.
87Schweyen R, Hey J, Fränzel W, Vordermark D, Hildebrandt G, Kuhnt T. Radiation-related caries: Etiology and possible preventive strategies. What should the radiotherapist know?. Strahlenther Onkol 2012;188:21-8.
88Hong 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.
89Michelet M. Caries and periodontal disease in cancer survivors. Evid Based Dent 2012;13:70-3.
90Taneja MK. Life style management in head and neck cancer patients. Indian J Otolaryngol Head Neck Surg 2013;65:289-92.
91Villaret AB, Cappiello J, Piazza C, Pedruzzi B, Nicolai P. Quality of life in patients treated for cancer of the oral cavity requiring reconstruction: A prospective study. Acta Otorhinolaryngol Ital 2008;28:120-5.
92Vickery LE, Latchford G, Hewison J, Bellew M, Feber T. The impact of head and neck cancer and facial disfigurement on the quality of life of patients and their partners. Head Neck 2003;25:289-96.
93Callahan C. Facial disfigurement and sense of self in head and neck cancer. Soc Work Health Care 2004;40:73-87.
94Verdonck-de Leeuw IM, Eerenstein SE, Van der Linden MH, Kuik DJ, de Bree R, Leemans CR. Distress in spouses and patients after treatment for head and neck cancer. Laryngoscope 2007;117:238-41.
95Hassanein KA, Musgrove BT, Bradbury E. Functional status of patients with oral cancer and its relation to style of coping, social support and psychological status. Br J Oral Maxillofac Surg 2001;39:340-5.
96Argerakis GP. Psychosocial considerations of the post-treatment of head and neck cancer patients. Dent Clin North Am 1990;34:285-305.
97Semple C, Parahoo K, Norman A, McCaughan E, Humphris G, Mills M. Psychosocial interventions for patients with head and neck cancer. Cochrane Database Syst Rev 2013;7:CD009441. Published 2013 Jul 16. doi:10.1002/14651858.CD009441.pub2.
98Adsett CA. Emotional reactions to disfigurement from cancer therapy. Can Med Assoc J 1963;89:385-91.
99Partridge J. Facial disfigurement. Both counselling for patients and education for the public are necessary. BMJ 1997;315:120.
100Edwards D. Facial disfigurement. Counselling is important in healing the whole patient. BMJ 1997;315:120.
101Sultan A, Hanna GJ, Margalit DN, et al. The Use of Hyperbaric Oxygen for the Prevention and Management of Osteoradionecrosis of the Jaw: A Dana-Farber/Brigham and Women's Cancer Center Multidisciplinary Guideline [published correction appears in Oncologist 2017;22:1413]. Oncologist 2017;22:343-50. doi:10.1634/theoncologist.2016-0298.
102Chronopoulos A, Zarra T, Ehrenfeld M, Otto S. Osteoradionecrosis of the jaws: Definition, epidemiology, staging and clinical and radiological findings. A concise review. Int Dent J 2018;68:22-30.
103Zehr L. Osteoradionecrosis, mandible. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2017.
104Jereczek-Fossa BA, Orecchia R. Radiotherapy-induced mandibular bone complications. Cancer Treat Rev 2002;28:65-74.
105Chrcanovic BR, Reher P, Sousa AA, Harris M. Osteoradionecrosis of the jaws—a current overview—part 1: Physiopathology and risk and predisposing factors. Oral Maxillofac Surg 2010;14:3-16.
106Hanley M, Cooper J. Osteoradionecrosis. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2017.
107Caparrotti F, Huang SH, Lu L, Bratman SV, Ringash J, Bayley A, et al. Osteoradionecrosis of the mandible in patients with oropharyngeal carcinoma treated with intensity-modulated radiotherapy. Cancer 2017;123:3691-700.
108Nabil S, Samman N. Incidence and prevention of osteoradionecrosis after dental extraction in irradiated patients: A systematic review. Int J Oral Maxillofac Surg 2011;40:229-43.
109Koga DH, Salvajoli JV, Alves FA. Dental extractions and radiotherapy in head and neck oncology: Review of the literature. Oral Dis 2008;14:40-4.
110Sulaiman F, Huryn JM, Zlotolow IM. Dental extractions in the irradiated head and neck patient: A retrospective analysis of Memorial Sloan-Kettering Cancer Center protocols, criteria, and end results. J Oral Maxillofac Surg 2003;61:1123-31.
111Reuther T, Schuster T, Mende U, Kübler A. Osteoradionecrosis of the jaws as a side effect of radiotherapy of head and neck tumour patients—a report of a thirty year retrospective review. Int J Oral Maxillofac Surg 2003;32:289-95.
112Loh SY, Mcleod RWJ, Elhassan HA. Trismus following different treatment modalities for head and neck cancer: A systematic review of subjective measures. Eur Arch Otorhinolaryngol 2017;274:2695-707.
113Teguh DN, Levendag PC, Voet P, van der Est H, Noever I, de Kruijf W, et al. Trismus in patients with oropharyngeal cancer: Relationship with dose in structures of mastication apparatus. Head Neck 2008;30:622-30.
114van der Molen L, van Rossum MA, Burkhead LM, Smeele LE, Rasch CR, Hilgers FJ. A randomized preventive rehabilitation trial in advanced head and neck cancer patients treated with chemoradiotherapy: Feasibility, compliance, and short-term effects. Dysphagia 2011;26:155-70.
115Nagaraja S, Kadam SA, Selvaraj K, Ahmed I, Javarappa R. Trismus in head and neck cancer patients treated by telecobalt and effect of early rehabilitation measures. J Cancer Res Ther 2016;12:685-8.
116Access Angst: A CDHA Position Paper on Access to Oral Health Services. The Canadian Dental Hygienists' Association; 23 March, 2003. Available from: http://www.cdha.ca/pdfs/Profession/Resources/position_paper_access_angst.pdf. [Last accessed on 2017 Jul 01].
117Samim F, Epstein JB, Zumsteg ZS, Ho AS, Barasch A. Oral and dental health in head and neck cancer survivors. Cancers Head Neck 2016;1:14.
118Khalid M, Hassani D, Bilal M, Butt ZA, Hamayun M, Ahmad A, et al. Identification of oral cavity biofilm forming bacteria and determination of their growth inhibition by Acacia arabica, Tamarix aphylla L. and Melia azedarach L. medicinal plants. Arch Oral Biol 2017;81:175-85.
119Hashim D, Sartori S, Brennan P, Curado MP, Wünsch-Filho V, Divaris K, et al. The role of oral hygiene in head and neck cancer: Results from International Head and Neck Cancer Epidemiology (INHANCE) consortium. Ann Oncol 2016;27:1619-25.
120Chen AM, Daly ME, Vazquez E, Courquin J, Luu Q, Donald PJ, et al. Depression among long-term survivors of head and neck cancer treated with radiation therapy. JAMA Otolaryngol Head Neck Surg 2013;139:885-9.
121Balcı Şengül MC, Kaya V, Şen CA, Kaya K. Association between suicidal ideation and behavior, and depression, anxiety, and perceived social support in cancer patients. Med Sci Monit 2014;20:329-36.
122Suicide Rate High in Patients with Head and Neck Cancer. Parsippany, NJ, USA.: Frontline Medical Communications Inc.; 2015. Available from: http://www.mdedge.com/clinicalpsychiatrynews/article/104337/head-neck-cancers/suicide-rate-high-patients-head-and-neck. [Last accessed on 2017 Jul 01].
123Oral Complications of Cancer Treatment: What the Dental Team Can Do. Available from: http://www.nidcr.nih.gov/oralhealth/topics/cancertreatment/oralcomplicationscanceroral.htm. [Last accessed on 2017 Jun 06].
124Lawrence M, Aleid W, McKechnie A. Access to dental services for head and neck cancer patients. Br J Oral Maxillofac Surg 2013;51:404-7.
125Epstein JB, Güneri P, Barasch A. Appropriate and necessary oral care for people with cancer: Guidance to obtain the right oral and dental care at the right time. Support Care Cancer 2014;22:1981-8.
126Andrews N, Griffiths C. Dental complications of head and neck radiotherapy: Part 2. Aust Dent J 2001;46:174-82.
127Rhodes-Nesset S, Laronde DM. Dental hygiene care of the head and neck cancer patient and survivor. Cancer J Dent Hyg 2014;48:20-6.
128Yellowitz J, Horowitz AM, Goodman HS, Canto MT, Farooq NS. Knowledge, opinions and practices of general dentists regarding oral cancer: A pilot survey. J Am Dent Assoc 1998;129:579-83.
129Applebaum E, Ruhlen TN, Kronenberg FR, Hayes C, Peters ES. Oral cancer knowledge, attitudes and practices: A survey of dentists and primary care physicians in Massachusetts. J Am Dent Assoc 2009;140:461-7.
130Patton LL, Elter JR, Southerland JH, Strauss RP. Knowledge of oral cancer risk factors and diagnostic concepts among North Carolina dentists. Implications for diagnosis and referral. J Am Dent Assoc 2005;136:602-10.
131Pakfetrat A, Falaki F, Esmaily HO, Shabestari S. Oral cancer knowledge among patients referred to Mashhad Dental School, Iran. Arch Iran Med 2010;13:543-8.
132López-Jornet P, Camacho-Alonso F, Molina-Miñano F. Knowledge and attitudes about oral cancer among dentists in Spain. J Eval Clin Pract 2010;16:129-33.
133Razavi SM, Zolfaghari B, Foroohandeh M, Doost ME, Tahani B. Dentists' knowledge, attitude, and practice regarding oral cancer in Iran. J Cancer Educ 2013;28:335-41.
134Forrest JL, Horowitz AM, Shmuely Y. Dental hygienists' knowledge, opinions, and practices related to oral and pharyngeal cancer risk assessment. J Dent Hyg 2001;75:271-81.
135Patel Y, Bahlhorn H, Zafar S, Zwetchkenbaum S, Eisbruch A, Murdoch-Kinch CA. Survey of Michigan dentists and radiation oncologists on oral care of patients undergoing head and neck radiation therapy. J Mich Dent Assoc 2012;94:34-45.
136Vijay Kumar KV, Suresan V. Knowledge, attitude and screening practices of general dentists concerning oral cancer in Bangalore city. Indian J Cancer 2012;49:33-8.