20Q: Head and Neck Cancer for the Speech-Language Pathologist

From the Desk of Ann Kummer

Head and neck cancer includes different malignant tumors that occur in or around the mouth, throat, larynx, nose, and sinuses. Head and neck cancer is curable if detected early. Head and neck cancers are generally treated with various combinations of surgery, radiation, and chemotherapy. Head and neck cancer and the toxicities of treatment affect structures important for speech, voice, and swallowing. Therefore, speech-language pathologists are usually involved in post-treatment rehabilitation. Therefore, I'm pleased that Dr. Barbara Pisano Messing, an expert on this topic, will answer common questions regarding the evaluation and treatment of head and neck cancer in the 20Q article.

Barbara Pisano Messing, PhD., CCC-SLP, BCS-S, FASHA, is a medical speech pathologist with over 36 years of clinical and leadership experience. She is a Clinical Specialist in Head and Neck Rehabilitation and a Board-Certified Specialist in Swallowing and Swallowing Disorders. Dr. Messing was the administrative-clinical director of the Milton J. Dance, Jr. Head and Neck Center, Head and Neck Surgery, and Johns Hopkins Voice Center at GBMC in Baltimore, Maryland, for 22 years. She has lectured nationally and internationally on dysphagia and published in peer-reviewed journals on managing patients with head and neck cancer and voice disorders. Her clinical and research interests are in the area of head and neck cancer rehabilitation, dysphagia, and voice disorders.

Now…read on, learn, and enjoy!

Ann W. Kummer, PhD, CCC-SLP, FASHA, 2017 ASHA Honors
Contributing Editor 

Browse the complete collection of 20Q with Ann Kummer CEU articles at www.speechpathology.com/20Q

20Q: Head and Neck Cancer for the Speech-Language Pathologist 

Learning Outcomes

After this course, readers will be able to: 

• Discuss head and neck cancer presentation from diagnosis to treatment planning
• Identify current surgical approaches and reconstruction options for the management of HNC
• Discuss the impact on swallowing for patients undergoing surgical and reconstructive management
• Describe the difference between potential surgical approaches and reconstruction options based on tumor and patient factors

Barbara Messing

1. I understand that Head and Neck Cancer (HNC) is a devastating disease affecting men and women of all ages worldwide. What are the current statistical trends for people with head and neck cancer?

The American Cancer Society estimates that 4% of all new cancers in the United States are head and neck cancers (HNC). In 2022, approximately 66,470 people will be diagnosed with HNC. The distribution of new HNC cases by gender is more significant in men vs. women (48,520 males; 17,950 females). The worldwide incidence of new HNC cases in 2020 was an estimated 562,328, with 277,597 deaths. In the United States, there were 15,050 HNC-related deaths (10,940 men and 4,110 women) in 2020.

Head and neck cancer statistics may seem low compared to the estimated 1,918,030 new cancer cases (all types), with approximately 5250 diagnosed daily (Siegel et al., 2020). However, HNC tumor and treatment-related effects may significantly impact functional speech, voicing, and swallowing with short-term and long-term deficits. Additionally, worldwide incident rates vary with geographical location, gender, race, ethnicity, and risk factors (Argiris et al., 2008; Howlader, 2017).

2. What are some considerations for HNC patients when seeking treatment for suspected head and neck tumors?

The complexities of HNC require a specialized, multidisciplinary team to achieve optimal oncologic and survival benefits. Intensive intervention from a team of HNC surgeons, medical oncologists, radiation oncologists, speech-language pathologists, oncology nurses, oncology dietitians, and oncology social workers is needed to preserve function, minimize detrimental tumor and treatment-related effects, and maximize functional recovery. The specialized HNC team works together with the patient and caregivers to improve survival benefits and quality of life during and post-treatment.

As the HNC multidisciplinary team aims for oncologic control, function, and quality of life, other important factors, including the patient’s voice, performance status, tumor pathology, and procedure and treatment selection, should be considered with collaborative efforts to achieve optimal results.

3. What are the early and long-term treatment-related effects encountered by many HNC patients?

Despite the best efforts of the multidisciplinary team, many patients undergoing HNC management will experience multiple short and long-term functional changes, most significantly, dysphagia, that have the potential to negatively affect their overall quality of life (Garcia-Peris et al., 2007; Murphy & Gilbert, 2009; Petkar et al., 2016; Platteaux et al., 2010; Rosenthal et al., 2006; Wang & Eisbruch, 2016; Ziegler et al., 2004). HNC patients are at high risk of experiencing early and long-term toxicities resulting in physiological, functional, and sensory deficits impacting health-related quality of life (HRQOL) (Barnhart et al., 2018; Dirix et al., 2009; Tribius et al., 2015). Early treatment-related toxicities include oropharyngeal mucositis, pain, xerostomia, dysgeusia, odynophagia, nausea, fatigue, neuropathy, and edema.

4. When a patient presents with a head and neck tumor, it can be painful and impact eating/swallowing and voicing depending on the location, extension, and size of the tumor. Is surgery the best option for treatment of HNC tumors?

Surgical interventions for HNC have been a primary treatment modality for many centuries and continue to play an integral role with new surgical advances. HNC surgical and reconstructive goals are to achieve oncologic control while optimizing functional outcomes. Surgical and non-surgical medical approaches to the management of head and neck cancer aim to improve survival, cosmesis, speech and swallow function, and maximize quality of life (QOL). While curative treatment is often the goal, optimal functional outcomes are not always attainable due to the influences of tumor size and extension and other treatment-related toxicities. Patients with larger tumors and extracapsular spread or extension and lymphatic invasion to the lymph nodes in the neck may require adjuvant treatment with radiation and chemotherapy. Treatment-related toxicities such as dysphagia, xerostomia, dysgeusia, lymphedema, and other issues may impact the patient's early and long-term recovery and impact quality of life.

5. Primary surgery for treatment of HNC tumors results in a surgical defect area once the tumor is removed. What are some considerations when surgery is the primary treatment for the head and neck tumor?

The history of head and neck cancer treatment has shifted from radical surgery to chemoradiation therapy and, more recently, to a treatment approach tailored to a patient’s unique physiologic status while trying to achieve oncologic control, positive functional results, and the best possible quality of life. Reconstruction considerations include tumor size and stage, anticipated surgical defect, impact on function, previous HNC treatments, patients' age and medical comorbidities, the potential for airway compromise, and cosmesis. HNC surgeons with specialized skills can perform minimally invasive techniques. Compared to traditional open surgical approaches to oropharyngeal tumors, minimally invasive transoral robotic surgical (TORS) approaches significantly decrease morbidity. Additional benefits of TORS are excellent oncologic results and reduced length of hospitalization (reduced from 7 to 10 days to 2 to 4 days on average).

6. Human papillomavirus (HPV) is a sexually transmitted pathogen that is etiologically responsible for a growing subset of oropharyngeal squamous cell carcinomas (OPSCC). Over the past decade, there has been more research on the human papillomavirus (HPV) and its relationship to HNC tumors. Is HPV known to contribute to HNC tumors?

Viral etiology has been linked to HNC formation, such as the human papillomavirus (HPV) and the Epstein-Barr virus (EBV). Historical patterns revealed the incidence of HNC in the United States decreased significantly from 1974 to 1999, however, at the same time a rise in the incidence of OPC was reported, possibly explained by virally mediated. With respect to HPV-related HNC, it is estimated that 60-70% of HNCs are attributable to the HPV and most often related to oropharyngeal squamous cell carcinoma (OPSCC) in the lingual and palatine tonsils and base of tongue (Cohen et al., 2016; Marur & Forastiere, 2008). Since 1983 there has been a notable increase in OPSCCs in HPV-positive, younger men and women (< 60 years of age) internationally indicating HPV as a potential factor in the increasing incidence of OPSCC worldwide (Chaturvedi et al., 2013). A study by Gooi et al in 2016 stated that there is a 3 to 10-fold higher rate of HPV-positive OPSCCs with anticipation that rates will continue to increase (Gooi et al., 2016b).

7. HPV-positive OPSCC is on the rise as reported by Gooi et al. (2016). What factors indicate that patients with HPV-positive OPSCC may have a better prognosis than HPV-negative OPSCC?

HPV-positive tumors are most often located in the lingual tonsils, palatine tonsils, or base of tongue.  In early-stage primary-site disease treated in a timely manner, patients may have better survival outcomes than in a more advanced stage. HNC presenting with HPV-positive OPSCC have generally been younger with fewer comorbidities and less likely to have a heavy smoking history potentially resulting in improved oncologic outcome and survival (Dong et al., 2021). Improved mortality rates for early-stage head and neck tumors are contributing to greater numbers of patients surviving the effects of HNC and its management for these tumors. Also, trends in smoking have been linked to incidences of lung cancer with an observed decline in lung cancer with a corresponding increase in OPSCCs, thereby potentially linking HPV as a contributing risk factor to the rising incidence of HPV-related OPSCC (Chaturvedi et al., 2008). Considering patient and tumor characteristics (e.g., cancer staging for OPSCC), pathology, and risk factors (i.e., tobacco and alcohol use and medical history/comorbidities), patients with HPV-positive OPSCC may have better overall survival (https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1437).

8. There has been extensive research in the area of HPV-related OPSCC and treatment outcomes over the past few decades. What are some of the findings from recent studies in this area?

Over the past few years, research has shown that the biological entities of HPV-positive OPSCC differ from HPV-negative OPSCC, however, more research is needed to determine the appropriate treatment recommendations and whether de-escalation (less intensive) treatment is indicated without a negative impact on survival outcomes (Bigelow et al., 2020). Future research trials are needed to study optimal treatment for HPV-related OPSCC to ensure survival outcomes are not negatively impacted by de-escalation protocols (Mirghani & Blanchard, 2018). Recent results from two large de-escalation trials resulted in unexpected findings suggesting an inferior survival outcome compared to standard therapy for HPV-positive patients (Ventz et al., 2019). More research is needed to better understand the biology of HPV-positive OPSCC and implications for future research and treatment protocols that aim to reduce treatment-related toxicities and increase overall survival outcomes.

9. Ongoing research investigating treatment de-escalation for HPV-related OPC seeks to determine which patients will benefit from less intensive protocols without having a detrimental effect on patient survival outcomes (Bigelow et al., 2020). What other benefits should future research demonstrate deintensified treatment would be indicated for select patient populations who present with HPV-positive OPSCC?

Mirghani et al. (2018) reported that only “low-risk” patients may be eligible for less intensive treatment but additional clinical trials are needed. Patients with more advanced HNC will undergo standard-of-care treatment, that is, surgery, +/- radiation therapy with or without chemotherapy and they will suffer significant treatment-related toxicities. De-escalation treatment will reduce treatment-related toxicities and improve patients' function and lessen the negative effects of treatment. Patients may have better swallow function, as well as fewer symptoms of dry mouth and taste loss, early and long-term, contributing to better overall HRQOL. In fact, in 2018, a new staging system was published by the American Joint Committee on Cancer (AJCC) with changes in the treatment protocols considering a deintensification protocol for HPV-positive OPSCC tumors with the goal of reducing early and long-term treatment-related effects.

10. It is known that HNC patients suffer early and long-term effects of tumor and treatment-related toxicities. What are the most common tumor and treatment-related effects that patients should be educated about and managed by the HNC multidisciplinary team?

HNC patients are at high risk of experiencing early and long-term toxicities resulting in physiological, functional, and sensory deficits impacting HRQOL (Barnhart et al., 2018; Dirix et al., 2009; Tribius et al., 2015). Early treatment-related toxicities include oropharyngeal mucositis, pain, xerostomia, dysgeusia, odynophagia, nausea, fatigue, neuropathy, and edema. These symptoms often contribute to dysphagia, reduced oral intake, weight loss, gastrostomy tube dependency, reduced nutritional intake, lymphedema, fibrosis, trismus, and muscle atrophy (Barnhart et al., 2018; Hawkins et al., 2018; Kraaijenga et al., 2016; Kraaijenga et al., 2015; Kraaijenga et al., 2017; Kraaijenga et al., 2014; B. P. Messing et al., 2017; Moroney et al., 2017; Siddiqui & Movsas, 2017). Technological advances in HNC management have contributed to improved tumor control and better survival outcomes, yet early and late toxicities persist with potentially negative consequences on the patient’s HRQOL (Dirix & Nuyts, 2010; Hammerlid et al., 2017; Hawkins et al., 2018; Pulte & Brenner, 2010; Trotti et al., 2003). Severe and complex tumor and treatment-related toxicities may occur from the primary tumor, surgery, radiation, and chemotherapy treatments. Some of these symptoms and anatomical changes result in collateral damage from excision of the primary tumor site and adjacent anatomical areas, mucositis, pain, hyposalivation, dysphagia, stricture, dysgeusia, nausea, fatigue, neuropathy, edema, internal and external lymphedema, fibrosis, trismus, muscle atrophy, malnutrition, weight loss, and cachexia (B. Messing et al., 2017). Other studies report treatment toxicities and a pattern of symptoms compromising patients’ swallow function and oral intake, resulting in potentially life-threatening complications such as severe dysphagia and aspiration pneumonia (Barnhart et al., 2018; Dirix et al., 2009; Dirix & Nuyts, 2010; Hawkins et al., 2018; Kamal et al., 2018).

11. It seems as though patients who present with HNC will experience pain and other symptoms that would affect their quality of life. What is the impact of long-term treatment-related effects on patients’ quality of life?

Several recent studies report the loss of function post-treatment, with persistent toxicities impacting HRQOL (Barnhart et al., 2018; Dirix et al., 2009; Hawkins et al., 2018; Kamal et al., 2018; Wan Leung et al., 2011). Lazarus et al. (Lazarus et al., 2014) reported that dry mouth, voice, and speech problems tend to persist long-term. HNC treatment-toxicities result in impaired function, including reduced tongue strength, restricted incisal opening, and other physiological swallow impairments with adverse effects on HRQOL (Lazarus et al., 2014). Long-term symptoms of taste alteration and dry mouth contribute to difficulties chewing and swallowing, reduced oral intake, restricted diet level, fatigue, anxiety, depression, osteoradionecrosis, and poorer HRQOL over time (Barnhart et al., 2018; Dirix et al., 2009; Dirix & Nuyts, 2010; Hawkins et al., 2018; Kamal et al., 2018; Quinten et al., 2011).

Effects of treatment often persist which highlights the importance of investigating patient outcomes long-term. Recent research highlighted treatment-related toxicities' impact on oral intake based on patient-report from HRQOL tools. In a long-term prospective study of treatment-related toxicities and impacts on oral intake, Barnhart et al. (2018) reported that many treatment toxicities resolved over time, with improved oral intake and fewer barriers to eating well by 6 months post-treatment. Barnhart et al. (2018) reported that the severity of dry mouth and taste changes persisted long-term, however, patient perceptions of these symptoms on oral intake lessened somewhat over time. Such data show that patients may experience a degree of adaptation to long-term deficits, potentially leading to a lessening of perceived influence on HRQOL.

12. As noted above, HNC patients experience significant treatment-related effects both early and long-term. What can the HNC multidisciplinary team do to monitor and track patients' functional and physical symptoms as well as health-related quality of life (HRQOL)?

Tumor characteristics (site-stage) and treatment modalities, whether surgical, non-surgical, or mixed, influence recovery and contribute to persistent issues in different ways. Worsening of symptoms and patterns of functional loss and recovery from HNC treatments may affect the quality of patient survivorship and HRQOL. Patient education on treatment-related toxicities and survivorship outcomes associated with specific treatment approaches may help increase patient involvement in treatment decisions and impact their early and long-term quality of life (Paleri et al., 2014; van Linden van den Heuvell et al., 2017). Members of the HNC multidisciplinary team may gain valuable information through monitoring patients longitudinally using self-reported quality-of-life questionnaires to better understand the extent and impact of these functional deficits and symptomatic issues reported from a patient-centered vantage point (Barnhart et al., 2018; Quinten et al., 2011; Quon et al., 2016). There are many HRQOL questionnaires available. For example, the European Organization of Research and Treatment of Cancer (EORTC) QoL Questionnaires - Quality of Life Core Questionnaire (EORTC QLQ-C30) and the specific HNC module (EORTC QLQ-H&N35), are frequently used to monitor patient-reported changes of functional and symptom-related problems (Lazarus et al., 2014; Murphy et al., 2007; Yang et al., 2015).

13. HNC patients undergo different treatment protocols depending on the TNM stage (T = tumor size and location, N = local metastasis to the neck, and M = distant metastasis to other locations in the body). What are the implications of surgery on the HNC patient?

Surgery for the primary tumor and when there is a possible extension to more than one site alters anatomical structures and neurological processes depending on size and location of the tumor as well as type of reconstruction (Kreeft et al., 2009).

14.  If a patient presents with a tumor in the head and neck region and is recommended to undergo surgery as the primary treatment modality followed by radiation with or without chemotherapy, what is the primary goal of surgery?

The primary goal of surgery is curative intent with optimal post-surgical cosmoses along with consideration of swallow function, nutritional status, and quality of life. Surgical treatments in the head and neck have the potential to impact bolus formation, mastication, efficient and timely bolus transport, and airway protection.

15. Surgery for HNC patients can result in collateral damage to nearby anatomical structures. Are there minimally invasive surgical techniques that result in better swallowing outcomes?

The optimization of functional outcomes and quality of life is paramount to the rehabilitation of HNC patients. Minimally invasive techniques, such as transoral robotic surgery (TORS), have become widespread treatment modalities. Recent literature suggests patients who undergo TORS realize better swallow function post-treatment as compared to patients treated with chemoradiation (More et al., 2013).

16. If a patient presents with a tumor in the head and neck region and is recommended to undergo chemoradiation as the primary treatment, what are the current considerations and goals of chemoradiation protocols for the HNC patient?

Chemoradiation protocols are designed to achieve tumor control while preserving anatomical areas from extensive surgical procedures and reconstruction methods. The effects of radiation include vascular, muscle, connective tissue, bone, and salivary gland changes, occurring both early during treatment and continuing long-term post-treatment. Technological advances in delivering radiation therapy using Intensity Modulated Radiation Therapy (IMRT) (Ghosh et al., 2016) has lessened some of the impact burden of these treatments by minimizing the dose to critical anatomical structures involved in swallowing. IMRT is often combined with chemotherapy to maximize tumor control. Currently, HNC patients with advanced oropharyngeal cancer (OPC) treated with multimodalities continue to experience significant toxicities. Al-Mamgani et al. (2013) reported on 204 patients with advanced OPC requiring multimodality treatment of CRT and found that oncologic outcomes were improved – however, this came with increased burden of significant toxicities. Chemotherapy was also found to increase the level of toxicities suffered by patients with dysphagia and xerostomia persisting long-term (Al-Mamgani et al., 2013).

17. HNC patients may present with mild to severe swallowing difficulties. What is the impact of HNC treatments on swallowing function?

Although HNC treatments target malignancies, they trigger a multitude of treatment-related toxicities that transiently or permanently alter anatomical structures and function essential for swallowing safety, oral intake, and quality of life. Treatments for HNC contribute to the disruption of critical functions, such as feeding, eating, and swallowing, resulting in life-altering changes and potentially death (Chera et al., 2014; Nguyen et al., 2005). Critical anatomical and physiological swallowing structures or dysphagia/aspiration-related structures (DARS) (Eisbruch et al., 2004) are at high risk of mucosal and structural damage from intensive treatment likely contributing to late and ongoing dysphagia and aspiration (Eisbruch et al., 2004). Surgery, radiation, and/or chemotherapy are selected with the intent to cure HNC. However, the tumor and treatment(s) disrupt normal function. Disuse quickly results in muscle atrophy from reduced muscle use, movement, and motion. Muscle atrophy results in reduced frequency of swallow, edema, and lymphedema (King et al., 2016). Muscle fibrosis, tissue scarring, anatomical changes from excision of structures, muscle atrophy from neuromuscular changes, cranial nerve denervation, stricture, trismus, xerostomia, and taste loss all increase the risk and severity of dysphagia and malnutrition post-treatment. Long-term effects of muscle atrophy from disuse result in tissue and muscle fiber changes resulting in fibrosis and functional abnormalities contributing to moderate or severe oropharyngeal dysphagia (King et al., 2016).

18. What is the symptom burden for the HNC patient?

The intensity level of symptom burden increases during and post-treatment resulting in a rapid decline in function and physical health status with devastating effects on psychosocial well-being and overall HRQOL (Murphy et al., 2007). These symptoms often contribute to dysphagia, reduced oral intake, weight loss, gastrostomy tube dependency, reduced nutritional intake, lymphedema, fibrosis, trismus, and muscle atrophy (Barnhart et al., 2018; Hawkins et al., 2018; Kraaijenga et al., 2016; Kraaijenga et al., 2015; Kraaijenga et al., 2017; Kraaijenga et al., 2014; B. P. Messing et al., 2017; Moroney et al., 2017; Siddiqui & Movsas, 2017). Several recent studies report the loss of function post-treatment, with persistent toxicities impacting HRQOL (Barnhart et al., 2018; Dirix et al., 2009; Hawkins et al., 2018; Kamal et al., 2018; Wan Leung et al., 2011). Lazarus et al. (Lazarus et al., 2014) reported that dry mouth, voice, and speech problems tend to persist long-term. Depending on the HNC stage, comorbidities, age, risk factors, and previous cancer history, patients suffer treatment-related toxicities that impair function, including reduced tongue strength, restricted incisal opening, and other physiological swallow impairments with adverse effects on HRQOL (Lazarus et al., 2014).

19. HNC patients are faced with a diagnosis that unexpectedly disrupts their normal daily life, activities of daily living, relationships and normal function. How does the HNC patient manage their symptoms and life changes over time?

Early and long-term monitoring of HRQOL increases our understanding of the impact that persistent symptoms may have on an HNC patient. Studies report that many patients will adjust to ongoing persistent symptoms and come to accept a ‘new normal’ (Barnhart et al., 2018; Nund et al., 2014). Findings from a recent study showed that even though patients continued to report moderate-severe dry mouth long-term, Global QoL scores remained consistently higher (Braam et al., 2007). Recent research showed that patients perceived the impacts of taste changes and dry mouth to lessen over time even though the presence of these symptoms had not improved (Barnhart et al., 2018). Hence a level of adjustment to these ongoing issues is assumed to have occurred. For some patients, persistent symptoms may continue to contribute to increased levels of distress and anxiety (Nguyen et al., 2005). Ongoing, longitudinal monitoring of the patient’s ability to cope post-treatment is critical to ensure timely management of any adverse psychological impacts, with early implementation of strategies to assist adjustment and improve HRQOL.

20. Surgical and non-surgical medical approaches to the management of head and neck cancer aim to improve survival, cosmesis, speech and swallow function, and maximize quality of life. What are some of the physiological and structural changes from HNC treatments?

Tumors that develop anywhere in the nerves, muscles, or other structures in the swallow mechanism can cause problems with swallowing. Surgery, radiation, and/or chemotherapy for head and neck cancer can significantly impair a patient's ability to speak or swallow and contribute to a multitude of physiological and structural changes. Surgical treatments in the head and neck have the potential to impact bolus formation, mastication, efficient and timely bolus transport, and airway protection. Initial surgery, +/- reconstruction, and adjuvant treatment (radiation and/or chemotherapy) are indicated in patients presenting with advanced disease. Multimodality protocols are needed for curative intent; however, the treatments contribute to additional negative impact on swallow function early and long term. Patients who undergo surgery and require post-operative chemoradiotherapy experience additional acute and long-term treatment-related toxicities.

References

Al-Mamgani, A., van Rooij, P., Verduijn, G. M., Mehilal, R., Kerrebijn, J. D., & Levendag, P. C. (2013). The impact of treatment modality and radiation technique on outcomes and toxicity of patients with locally advanced oropharyngeal cancer. Laryngoscope, 123(2), 386-393. 

Argiris, A., Karamouzis, M. V., Raben, D., & Ferris, R. L. (2008). Head and neck cancer. Lancet, 371(9625), 1695-1709.

Barnhart, M. K., Robinson, R. A., Simms, V. A., Ward, E. C., Cartmill, B., Chandler, S. J., & Smee, R. I. (2018). Treatment toxicities and their impact on oral intake following non-surgical management for head and neck cancer: a 3-year longitudinal study. Support Care Cancer, 26(7), 2341-2351. 

Bigelow, E. O., Seiwert, T. Y., & Fakhry, C. (2020). Deintensification of treatment for human papillomavirus-related oropharyngeal cancer: Current state and future directions. Oral Oncol, 105, 104652-104652. 

Braam, P. M., Roesink, J. M., Raaijmakers, C. P. J., Busschers, W. B., & Terhaard, C. H. J. (2007). Quality of life and salivary output in patients with head-and-neck cancer five years after radiotherapy.(Research). Radiat Oncol, 2.

Chaturvedi, A. K., Anderson, W. F., Lortet-Tieulent, J., Curado, M. P., Ferlay, J., Franceschi, S., Rosenberg, P. S., Bray, F., & Gillison, M. L. (2013). Worldwide trends in incidence rates for oral cavity and oropharyngeal cancers. J Clin Oncol, 31(36), 4550-4559. 

Chaturvedi, A. K., Engels, E. A., Anderson, W. F., & Gillison, M. L. (2008). Incidence trends for human papillomavirus-related and -unrelated oral squamous cell carcinomas in the United States. J Clin Oncol, 26(4), 612-619. 

Chera, B. S., Eisbruch, A., Murphy, B. A., Ridge, J. A., Gavin, P., Reeve, B. B., Bruner, D. W., & Movsas, B. (2014). Recommended patient-reported core set of symptoms to measure in head and neck cancer treatment trials. J Natl Cancer Inst, 106(7). 

Cohen, E., LaMonte, S. J., Erb, N. L., Beckman, K. L., Sadeghi, N., Hutcheson, K. A., Stubblefield, M. D., Abbott, D. M., Fisher, P. S., Stein, K. D., Lyman, G. H., & Pratt-Chapman, M. L. (2016). American Cancer Society Head and Neck Cancer Survivorship Care Guideline. CA Cancer J Clin, 66(3), 203-239. 

Dirix, P., Abbeel, S., Vanstraelen, B., Hermans, R., & Nuyts, S. (2009). Dysphagia after chemoradiotherapy for head-and-neck squamous cell carcinoma: dose-effect relationships for the swallowing structures. Int J Radiat Oncol Biol Phys, 75(2), 385-392. 

Dirix, P., & Nuyts, S. (2010). Evidence-based organ-sparing radiotherapy in head and neck cancer. Lancet Oncol, 11(1), 85-91. 

Dong, H., Shu, X., Xu, Q., Zhu, C., Kaufmann, A. M., Zheng, Z. M., Albers, A. E., & Qian, X. (2021). Current Status of Human Papillomavirus-Related Head and Neck Cancer: From Viral Genome to Patient Care. Virol Sin, 36(6), 1284-1302. 

Eisbruch, A., Schwartz, M., Rasch, C., Vineberg, K., Damen, E., Van As, C. J., Marsh, R., Pameijer, F. A., & Balm, A. J. (2004). Dysphagia and aspiration after chemoradiotherapy for head-and-neck cancer: which anatomic structures are affected and can they be spared by IMRT? Int J Radiat Oncol Biol Phys, 60(5), 1425-1439. 

Garcia-Peris, P., Paron, L., Velasco, C., de la Cuerda, C., Camblor, M., Breton, I., Herencia, H., Verdaguer, J., Navarro, C., & Clave, P. (2007). Long-term prevalence of oropharyngeal dysphagia in head and neck cancer patients: Impact on quality of life. Clin Nutr, 26(6), 710-717. 

Ghosh, G., Tallari, R., & Malviya, A. (2016). Toxicity Profile of IMRT Vs. 3D-CRT in Head and Neck Cancer: A Retrospective Study. Journal of clinical and diagnostic research : JCDR, 10(9), XC01-XC03. 

Gooi, Z., Chan, J. Y., & Fakhry, C. (2016). The epidemiology of the human papillomavirus related to oropharyngeal head and neck cancer. Laryngoscope, 126(4), 894-900. 

Hammerlid, E., Adnan, A., & Silander, E. (2017). Population-based reference values for the European Organization for Research and Treatment of Cancer Head and Neck module. Head &  Neck, 39(10), 2036-2047. 

Hawkins, P. G., Kadam, A. S., Jackson, W. C., & Eisbruch, A. (2018). Organ-Sparing in Radiotherapy for Head-and-Neck Cancer: Improving Quality of Life. Semin Radiat Oncol, 28(1), 46-52. 

Howlader, N., Noone, A. M., Krapcho, M., Garshell, J., Miller, D., Altekruse, S. F., ... & Mariotto, A. (2017). SEER Cancer Statistics Review, 1975-2014, National Cancer Institute. Bethesda, MD, https://seer.cancer.gov/csr/1975_2014/, based on November 2016 SEER data submission, posted to the SEER web site, April 2017. Retrieved April 2017 from https://seer.cancer.gov/statfacts/html/oralcav.html

Kamal, M., Rosenthal, D. I., Volpe, S., Goepfert, R. P., Garden, A. S., Hutcheson, K. A., Al Feghali, K. A., Meheissen, M. A. M., Eraj, S. A., Dursteler, A. E., Williams, B., Smith, J. B., Aymard, J. M., Berends, J., White, A. L., Frank, S. J., Morrison, W. H., Cardoso, R., Chambers, M. S., . . . Gunn, G. B. (2018). Patient reported dry mouth: Instrument comparison and model performance for correlation with quality of life in head and neck cancer survivors. Radiother Oncol, 126(1), 75-80. 

King, S. N., Dunlap, N. E., Tennant, P. A., & Pitts, T. (2016). Pathophysiology of Radiation-Induced Dysphagia in Head and Neck Cancer. Dysphagia, 31(3), 339-351. 

Kraaijenga, S. A., Oskam, I. M., van Son, R. J., Hamming-Vrieze, O., Hilgers, F. J., van den Brekel, M. W., & van der Molen, L. (2016). Assessment of voice, speech, and related quality of life in advanced head and neck cancer patients 10-years+ after chemoradiotherapy. Oral Oncol, 55, 24-30. 

Kraaijenga, S. A., van der Molen, L., Jacobi, I., Hamming-Vrieze, O., Hilgers, F. J., & van den Brekel, M. W. (2015). Prospective clinical study on long-term swallowing function and voice quality in advanced head and neck cancer patients treated with concurrent chemoradiotherapy and preventive swallowing exercises. Eur Arch Otorhinolaryngol, 272(11), 3521-3531. 

Kraaijenga, S. A. C., Molen, L. V., Stuiver, M. M., Takes, R. P., Al-Mamgani, A., Brekel, M., & Hilgers, F. J. M. (2017). Efficacy of a novel swallowing exercise program for chronic dysphagia in long-term head and neck cancer survivors. Head Neck, 39(10), 1943-1961. 

Kraaijenga, S. A. C., Van Der Molen, L., Van Den Brekel, M. W. M., & Hilgers, F. J. M. (2014). Current assessment and treatment strategies of dysphagia in head and neck cancer patients: a systematic review of the 2012/13 literature. Curr Opin Support Palliat Care, 8(2), 152-163. 

Kreeft, A. M., van der Molen, L., Hilgers, F. J., & Balm, A. J. (2009). Speech and swallowing after surgical treatment of advanced oral and oropharyngeal carcinoma: a systematic review of the literature. Eur Arch Otorhinolaryngol, 266(11), 1687-1698. 

Lazarus, C. L., Husaini, H., Hu, K., Culliney, B., Li, Z., Urken, M., Jacobson, A., Persky, M., Tran, T., Concert, C., Palacios, D., Metcalfe-Klaw, R., Kumar, M., Bennett, B., & Harrison, L. (2014). Functional outcomes and quality of life after chemoradiotherapy: baseline and 3 and 6 months post-treatment. Dysphagia, 29(3), 365-375. 

Marur, S., & Forastiere, A. A. (2008). Head and neck cancer: changing epidemiology, diagnosis, and treatment. Mayo Clin Proc, 83(4), 489-501. 

Messing, B., Ward, E., Lazarus, C., Kim, M., Zhou, X., Silinonte, J., Gold, D., Harrer, K., Ulmer, K., Merritt, S., Neuner, G., Levine, M., Blanco, R., Saunders, J., & Califano, J. (2017). Prophylactic Swallow Therapy for Patients with Head and Neck Cancer Undergoing Chemoradiotherapy: A Randomized Trial. Dedicated to advancing the art and science of deglutology, 32(4), 487-500. 

Messing, B. P., Ward, E. C., Lazarus, C. L., Kim, M., Zhou, X., Silinonte, J., Gold, D., Harrer, K., Ulmer, K., Merritt, S., Neuner, G., Levine, M., Blanco, R., Saunders, J., & Califano, J. (2017). Prophylactic Swallow Therapy for Patients with Head and Neck Cancer Undergoing Chemoradiotherapy: A Randomized Trial. Dysphagia, 32(4), 487-500.

Mirghani, H., & Blanchard, P. (2018). Treatment de-escalation for HPV-driven oropharyngeal cancer: Where do we stand? Clinical and Translational Radiation Oncology, 8, 4-11. 

Moroney, L. B., Helios, J., Ward, E. C., Crombie, J., Wockner, L. F., Burns, C. L., Spurgin, A. L., Blake, C., Kenny, L., & Hughes, B. G. (2017). Patterns of dysphagia and acute toxicities in patients with head and neck cancer undergoing helical IMRT+/-concurrent chemotherapy. Oral Oncol, 64, 1-8. 

Murphy, B. A., & Gilbert, J. (2009). Dysphagia in head and neck cancer patients treated with radiation: assessment, sequelae, and rehabilitation. Semin Radiat Oncol, 19(1), 35-42. 

Murphy, B. A., Ridner, S., Wells, N., & Dietrich, M. (2007). Quality of life research in head and neck cancer: a review of the current state of the science. Crit Rev Oncol Hematol, 62(3), 251-267. 

Nguyen, N. P., Frank, C., Moltz, C. C., Vos, P., Smith, H. J., Karlsson, U., Dutta, S., Midyett, A., Barloon, J., & Sallah, S. (2005). Impact of dysphagia on quality of life after treatment of head-and-neck cancer. Int J Radiat Oncol Biol Phys, 61(3), 772-778. 

Nund, R. L., Ward, E. C., Scarinci, N. A., Cartmill, B., Kuipers, P., & Porceddu, S. V. (2014). The lived experience of dysphagia following non-surgical treatment for head and neck cancer. Int J Speech Lang Pathol, 16(3), 282-289. 

Paleri, V., Roe, J. W., Strojan, P., Corry, J., Gregoire, V., Hamoir, M., Eisbruch, A., Mendenhall, W. M., Silver, C. E., Rinaldo, A., Takes, R. P., & Ferlito, A. (2014). Strategies to reduce long-term postchemoradiation dysphagia in patients with head and neck cancer: an evidence-based review. Head Neck, 36(3), 431-443. 

Petkar, I., Rooney, K., Roe, J. W., Patterson, J. M., Bernstein, D., Tyler, J. M., Emson, M. A., Morden, J. P., Mertens, K., Miles, E., Beasley, M., Roques, T., Bhide, S. A., Newbold, K. L., Harrington, K. J., Hall, E., & Nutting, C. M. (2016). DARS: a phase III randomised multicentre study of dysphagia- optimised intensity-modulated radiotherapy (Do-IMRT) versus standard intensity-modulated radiotherapy (S-IMRT) in head and neck cancer. BMC Cancer, 16(1), 770. 

Platteaux, N., Dirix, P., Dejaeger, E., & Nuyts, S. (2010). Dysphagia in head and neck cancer patients treated with chemoradiotherapy. Dysphagia, 25(2), 139-152. 

Pulte, D., & Brenner, H. (2010). Changes in Survival in Head and Neck Cancers in the Late 20th and Early 21st Century: A Period Analysis. Oncologist, 15(9), 994-1001. 

Quinten, C., Maringwa, J., Gotay, C. C., Martinelli, F., Coens, C., Reeve, B. B., Flechtner, H., Greimel, E., King, M., Osoba, D., Cleeland, C., Ringash, J., Schmucker-Von Koch, J., Taphoorn, M. J., Weis, J., & Bottomley, A. (2011). Patient self-reports of symptoms and clinician ratings as predictors of overall cancer survival. J Natl Cancer Inst, 103(24), 1851-1858. 

Quon, H., Hui, X., Cheng, Z., Robertson, S. P., Bowers, M. R., Moore, J., Choflet, A., Burns, L., Page, B. R., Kiess, A. P., Maclean, J., Wu, P., Omari, T., Szczesniak, M., Gourin, C. G., Cook, I. J., & McNutt, T. R. (2016). Quantitative Evaluation of Radiation-Induced Dysphagia Using Patient-Reported Outcome Instruments in the Development of a Personalized Head and Neck Cancer Treatment Deintensification Paradigm. In (Vol. 96, pp. E538-E538).

Rosenthal, D. I., Lewin, J. S., & Eisbruch, A. (2006). Prevention and treatment of dysphagia and aspiration after chemoradiation for head and neck cancer. J Clin Oncol, 24(17), 2636-2643. 

Siddiqui, F., & Movsas, B. (2017). Management of Radiation Toxicity in Head and Neck Cancers. Semin Radiat Oncol, 27(4), 340-349. 

Siegel, R. L., Miller, K. D., & Jemal, A. (2020). Cancer statistics, 2020. CA Cancer J Clin, 70(1), 7-30. 

Tribius, S., Raguse, M., Voigt, C., Münscher, A., Gröbe, A., Petersen, C., Krüll, A., Bergelt, C., & Singer, S. (2015). Residual deficits in quality of life one year after intensity-modulated radiotherapy for patients with locally advanced head and neck cancer. Journal of Radiation Oncology, Biology, Physics, 191(6), 501-510. 

Trotti, A., Colevas, A., Setser, A., Rusch, V., Jaques, D., Budach, V., Langer, C., Murphy, B., Cumberlin, R., & Coleman, C. (2003). CTCAE v3.0: development of a comprehensive grading system for the adverse effects of cancer treatment. Semin Radiat Oncol, 13(3), 176-181. 

van Linden van den Heuvell, C., van Zuuren, F., Wells, M., van der Laan, G., & Reintsema, H. (2017). Paradigm shift in head and neck oncology patient management. Journal of Otolaryngology-Head & Neck Surgery, 46, 57. 

Ventz, S., Trippa, L., & Schoenfeld, J. D. (2019). Lessons Learned from Deescalation Trials in Favorable Risk HPV-Associated Squamous Cell Head and Neck Cancer–A Perspective on Future Trial Designs. Clinical Cancer Research, 25(24), 7281-7286. 

Wan Leung, S., Lee, T. F., Chien, C. Y., Chao, P. J., Tsai, W. L., & Fang, F. M. (2011). Health-related quality of life in 640 head and neck cancer survivors after radiotherapy using EORTC QLQ-C30 and QLQ-H&N35 questionnaires. BMC Cancer, 11, 128. 

Wang, X., & Eisbruch, A. (2016). IMRT for head and neck cancer: reducing xerostomia and dysphagia. J Radiat Res, 57 Suppl 1, i69-i75. 

Yang, C. J., Roh, J. L., Choi, K. H., Kim, M. J., Choi, S. H., Nam, S. Y., & Kim, S. Y. (2015). Pretreatment Dysphagia Inventory and videofluorographic swallowing study as prognostic indicators of early survival outcomes in head and neck cancer. Cancer, 121(10), 1588-1598. 

Ziegler, L., Newell, R., Stafford, N., & Lewin, R. (2004). A literature review of head and neck cancer patients information needs, experiences and views regarding decision-making. Eur J Cancer Care (Engl), 13(2), 119-126.