Head-and-neck Cancer in the Emergency Department: A Contemporary Review of Common Presentations and Management

Abstract

Head-and-neck cancer (HNC) can present with life.threatening symptoms in the emergency department. Patients can sometimes be misdiagnosed with pulmonary disease due to similar signs and symptoms, ultimately leading to delayed diagnosis and potentially devastating consequences. Reasons for this include lack of awareness of patient risk factors and knowledge of the myriad of presenting complaints in the disease process among physicians working in primary care and in the emergency department. This article explores the contemporary risk factors and common presenting symptoms and discusses initial management for a patient with potential head-and-neck malignancy. Emergency presentations of HNC are wide ranging and can overlap with common respiratory pathologies. Clinician awareness of this can assist the team in deciding what appropriate examination and investigations are required to reduce the risk of delaying diagnosis and further treatment.

INTRODUCTION

Head-and-neck cancer (HNC) is the seventh most common cancer worldwide with mortality rates exceeding 50%.[1] HNC includes several different locations with a myriad of symptoms present at diagnosis making early detection challenging. Accordingly, the majority of patients with HNC are diagnosed at stage III or IV,[2] this being one of the strongest predictors of mortality.[3,4,5,6] Delayed diagnosis can be exacerbated by delays in presentation and referral from primary care as well as diagnosis and treatment in secondary care.[7] The emergency presentation of cancer is a significant burden, accounting for 24% of new diagnoses in England.[8] In HNC, around 10%–15% present via the emergency department and it translates into more advanced stage at diagnosis and worse survival outcomes.[9] Accordingly, there is a need for a better understanding of HNC presenting symptoms, so general practitioners and emergency department doctors can identify them early to improve diagnosis and prognosis.[10] This is particularly relevant when considering the increasing incidence of human papillomavirus (HPV)-related HNC that is changing the paradigm of patients with this disease.

Here, we conduct a contemporary review of the most common HNC risk factors and symptoms presenting in the emergency department and its initial management recommendations.

Risk factors for head-and-neck cancer

Knowledge of the risk factors for HNC is essential to be able to suspect this uncommon pathology. HNC is a cancer of adults, with a median age at diagnosis of 66 years for HPV-negative mucosal head-and-neck squamous cell carcinoma (HNSCC) and 53 years for HPV-positive HNSCC although it can be found in any age group. HNSCC is by enlarge the most common histological type of HNC. Therefore, we discuss its risk factors.

Smoking

Typically, HNSCC has been diagnosed in adults with a history of heavy tobacco and alcohol consumption. Tobacco causes a four- to five-fold increase in risk of developing oral cavity, oropharynx, and hypopharynx cancer alongside a 10-fold increased risk of laryngeal cancer.[11,12] Patients consuming 2 or more packets of tobacco a day in combination with alcohol have a 35-fold higher risk of developing HNSCC.[13,14] Historically, approximately 90% of patients with HNSCC had a history of tobacco use.[13] However, the incidence of HNSCC in this cohort of patients is slowly declining due to a decrease of consumption of these risk factors.[15]

Smokeless tobacco, areca nut, and betel quid

Smokeless tobacco, such as snuff or chewing tobacco, is an important HNSCC risk factor, particularly for cancers of the oral cavity.[16] There is an estimated 80% increase in risk of oral cavity cancer,[16] with a four-fold increase in odds of HNSCC among individuals who have used smokeless tobacco for at least 10 years compared to never-users.[17]

Alcohol

Alcohol independently increases the risk of HNC, with an estimated 1%–4% of cases attributable to alcohol alone,[13,18] and a two-fold increase in odds of HNSCC for drinkers who are never-users of tobacco.[19]

Human papillomavirus

HPV is a sexually transmitted infection known to be the putative precursor to HPV-related HNSCC (HPV-HNSCC), a distinct subset of HNSCC that occurs primarily in the oropharynx and arises from the lymphoid tissues of the palatine and lingual tonsils.[20] With more than 100 serotypes of HPV, only a small number of these are considered high risk or carcinogenic with most infections not progressing to cancer. HPV-16 is responsible for the vast majority of HPV-HNSCC.[21] The proportion of oropharyngeal cancers caused by HPV is growing;[22] therefore, awareness of the current epidemic of HPV-HNSCC is crucial for appropriate suspicion and early diagnosis. The average latency period of 10–30 years from initial oral infection to diagnosis of HPV oropharyngeal cancer means that risk factors may not be obvious at the moment of presenting symptoms.[23] HPV-HNSCC is more common in males and people with multiple lifetime sexual partners.[24]

Common symptoms in head-and-neck cancer

HNC includes cancers of the upper aerodigestive tract (oral cavity, nasopharynx, oropharynx, hypopharynx, and larynx), the paranasal sinuses, and the salivary glands. The anatomical sites affected are important for functions such as speech, breathing, and swallowing. Therefore, patients with HNC can manifest with impairment of those functions among other local and systemic symptoms.

Patients can present with systemic symptoms including cachexia, sarcopenia, weakness, chronic fatigue, or mood disorders among others.[25] The most common red flag symptoms encountered in the emergency department that should raise suspicion for HNC are described below. A higher level of suspicion is raised when these symptoms occur in combination and in a persistent pattern.

Airway obstruction

Airway obstruction is defined as narrowing or restriction of the airway leading to deterioration in ventilation. In relation to HNC, airway obstruction can occur due to direct extension of tumors, bilateral vocal cord palsy, or rarely, obstructive lymphedema.[26] It can be subdivided by severity (partial or complete) or chronicity (acute or chronic). In slowly progressive cancer, with conditioning of the respiratory muscles, patients may have few signs or symptoms despite significant narrowing of the airway. Good clinical history and examination are required to determine the urgency of treatment and further management. A high level of suspicion for HNC is required since it shares similar risk factors with pulmonary disease that can mimic symptoms and attribute to misdiagnosis. Symptoms pointing toward a diagnosis of airway obstruction include respiratory distress and stridor (high-pitched sound due to irregular flow of air in airways). A mild biphasic stridor can be mistaken for wheeze and can be misdiagnosed as obstructive pulmonary disease. The differential diagnosis of upper airway obstruction due to supraglottic or glottic narrowing should be kept in mind if patients do not respond to initial medical treatment [Figure 1].

Figure 1.

Airway obstruction

It is important to note that patients' oxygen saturation levels can often be unaffected during initial presentation. The cause of distress in this scenario is obstruction rather than compromised ventilation. Therefore, patients tend to maintain normal saturation levels at the expense of increasing ventilation rate and use of accessory muscles. Normal saturations can be falsely reassuring and could potentially lead to a delayed diagnosis and life-threatening upper airway obstruction. Associated symptoms that should raise the suspicion of airway obstruction rather than pulmonary disease are hoarseness, dysphagia, referred earache, weight loss, and/or neck mass. In an unstable patient with signs of respiratory distress or drooling, urgent assessment and management to ensure airway patency is mandatory. Evaluation of the airway should include an assessment of the difficulty in intubation and the feasibility of appropriate rescue plans in achieving oxygenation. Senior emergency department physicians and/or anesthetists should assess the patient for intubation to secure the airway. Besides checking for vital parameters, assessment includes evaluation of mouth opening, Mallampati test, size of mandibular space, and endoscopic examination when possible, being crucial when no radiological investigations are possible due to the time-critical nature of the situation. Awake fiberoptic intubation is the gold standard technique in this situation. The National Audit Project 4 report emphasized the importance of having an “airway management strategy” as opposed to a single plan and the timely sequential implementation of these plans for HNC.[27] Otolaryngology input is always recommended during intubation as there is a risk of requiring front-of-the-neck access. Patients can be optimized with humidified high-flow nasal oxygen while these interventions are executed.[28,29] For stable patients, consider nebulized adrenaline and intravenous steroids.

Neck mass

The primary concern of a slow-growing, persistent neck mass with no associated inflammatory signs in an adult is an underlying malignant pathology. The described pattern of lymphatic drainage is helpful in diagnosing the tumor primary site in HNC.[30] Accordingly, an accurate definition of the location of the mass, size, and other clinical features such as skin involvement, consistency of mass, and attachment to surrounding structures is mandatory. When a patient presents with a neck mass, a full detailed head-and-neck examination including skin and oral cavity is required. Patients with HPV-related cancers of the oropharynx most commonly present with a painless lateral neck mass and no other symptoms.[31] Because of the patient's young age, absence of risk factors, and unusual presentation, the symptoms might be confused with benign reactive nodal enlargement, thus delaying the diagnosis. Salivary gland tumors can also debut as a painless mass in the neck or side of the face in patients who are otherwise well. Accordingly, in all adults, a neck mass should be considered malignant until demonstrated otherwise and patients must be urgently referred to a head-and-neck specialist for further evaluation [Figure 2].

Figure 2.

Neck mass

Sore throat/throat pain

Sore throat is a common complaint with a vast differential diagnosis. From 2001 to 2002, the National Health Care Survey reported more than 21 million outpatient and emergency room visits with complaints relating to the throat.[32] By paying close attention to the associated symptoms and duration, common infectious etiologies such as viral tonsillitis or supraglottitis can be distinguished from HNC. The latter normally present with associated symptoms as described above and over a longer period of time such as weeks to months. Any sore throat that has persisted beyond 3 weeks and/or progression of sore throat with increasing pain or irritation warrants further investigation by a head-and-neck specialist. As the presenting complaint of sore throat may mean irritation, burning sensation, or frank pain, patients should be asked to elaborate on the description. Additionally, they should be asked to localize pain as it can refer to a variety of anatomical locations, for example, the entire pharynx and larynx or the soft tissues of the neck. Asking the patient to indicate the centre of discomfort in their neck can often aid in localisation of pathology. Persistent unilateral sore throat with otalgia is a frequent presenting complaint of HNC.[33,34]

Dysphagia

Dysphagia is a common symptom of complaint in the emergency department and is frequently present in patients with HNC profoundly diminishing quality of life.[35] In the emergency department, the management of these patients includes basic investigations aimed at diagnosing the cause and to understand the severity or chronicity of dysphagia. The first step is to rule out immediate life-threatening etiologies. Causes of dysphagia can be broadly classified anatomically into oropharyngeal or esophageal.[36] Acute neurological and life-threatening pathologies such as a stroke should be primarily investigated as dysphagia can be a common presenting problem. In this scenario, dysphagia is associated with other neurological symptoms such as unilateral weakness, facial drooping, or speech impairment.[37] When dysphagia is present in patients with HNC, it tends to develop progressively leading to malnutrition and dehydration as well as other local symptoms such as choking and aspiration pneumonia.[38] In contrast, these symptoms are rare in patients with esophageal causes.[36] Common findings which should raise the suspicion of HNC are the presence of a neck mass, nonhealing ulcers in the oral cavity, voice change, or cranial nerve involvement,[39] and accordingly, when present, urgent referral to an HNC specialist is recommended. Hospital admission should be considered for patients with respiratory complications or patients at high risk of malnourishment and dehydration. Patients should be kept nil by mouth and started on appropriate intravenous fluids if swallow is deemed unsafe. Odynophagia can be treated by optimizing pain relief, as discussed in the section “Pain management.” The UK HNC guidelines recommend that all patients have nutritional screening by a clinician at presentation and specialist dietician input throughout their care. The incidence of refeeding syndrome because of reintroduction of nutrients is high in HNC patients.[40] Refeeding syndrome occurs not only after starvation but also after periods of poor nutritional intake. As mentioned above, this is a common emergency presentation of HNC due to oropharyngeal dysphagia, cancer cachexia, and the high prevalence of alcoholism.[41] Refeeding syndrome is caused by hormonal and metabolic changes that lead to clinically significant hypophosphatemia, thiamine deficiency, and hypomagnesemia. Accordingly, serum electrolyte check is mandatory in the emergency department when malnourishment is suspected prior to re-instate feeding either enteral or parenteral.

Nonhealing ulcer

The association between chronic ulcer and HNSCC is well established. Its presentation, however, is varied, ranging from innocuous appearing lesions to overtly exophytic growths.[42] Although an ulcerated SCC is classically described to have prominent everted edges and a necrotic tumor base, these features are not always present, particularly in early stages of their development. For oral cancer, nonhealing ulcers or sores have been reported to be the very first symptom noted.[43] When associated with other head-and-neck symptoms or cranial nerve palsy, the suspicion for HNC should be high and urgent referral is indicated.

Unilateral recurrent epistaxis, nasal obstruction, and otalgia with normal ear examination or ear effusion

Patients with this problem should be considered for urgent referral to a head-and-neck surgeon who can do a full examination of the upper aerodigestive tract with an endoscopy to exclude nasal and postnasal space tumors.

Bleeding

Bleeding from HNC can be a life-threatening event and can occur from the tumor itself or due to the erosion of tumor into surrounding vascular structures. Carotid blowout syndrome can occur due to rupture of the carotid artery or branches caused by tumor erosion.[44] This syndrome has three distinct possible clinical presentations; a threatened blowout where there is a clinically exposed carotid artery or radiological evidence of tumor invasion of artery, an impending blowout whereby herald bleeding has settled or an acute, uncontrollable bleeding.[45] The last subgroup of patients should be escalated immediately to the anesthetic and otolaryngology team for further management. The patient should be sat upright and blood suctioned orally under direct vision to prevent any further bleeding. In the event of massive hemorrhage, the patient should be resuscitated and given blood products. Definitive management will depend on airway assessment; in severe cases, patients would require endotracheal intubation or front-of-the-neck access to secure the airway followed by surgical intervention or interventional radiology taking into consideration resources available at the hospital.

Management plan in the emergency department

Assessment

ABCDE approach is widely recognized and adapted in clinical practice for initial assessment of acutely unwell patients.[46] Assessment aims to identify and treat patients' most life-threatening problems first. In symptoms associated with HNC, this can often involve risk to the airway and breathing as described above. With patients presenting with any of the symptoms described, a full head-and-neck examination including skin and oral cavity and endoscopic examination when possible are required.

What tests are necessary?

Blood tests

Following thorough history and examination, blood tests such as full blood count, urea, electrolytes, renal function, C-reactive protein, and coagulation screen provide information on presenting complaints and potential complications. For example, patients with dysphagia can also present with raised infection markers secondary to aspiration pneumonia. Arterial blood gas gives indication to any ventilatory compromise and need for oxygen therapy. Urea, renal function, and electrolytes can provide information around degree of malnourishment and dehydration that the patient is presenting with.

Imaging

Imaging provides an indication of cause of symptoms and can aid in assessing patients' airway. In HNC, imaging can provide valuable information to diagnose potential complications and to rule out other pathologies causing symptoms. A chest X-ray in patients with respiratory distress and wheeze can indicate if the patient has chronic obstructive pulmonary disease (COPD) or aspiration pneumonia. As mentioned in the section “Airway obstruction,” HNC can be misdiagnosed with lower respiratory disease such as COPD which shares the same risk factors and is important to consider HNC in this situation. Accordingly, neck cross-sectional imaging can not only provide information about tumor extent and size, nodal disease, and tumor spread when HNC is confirmed but also diagnose the etiology when it is not clear on examination.

Endoscopy

When HNC is suspected, flexible nasal endoscopy can be performed to investigate the nasal cavity, pharynx, and larynx to provide further information on presenting complaints. Patients with symptoms of potential airway obstruction should undergo examination to inform further management, for example, impending airway obstruction which might require airway management with intubation or a tracheostomy. Patients presenting with oral bleeding with suspected HNC should undergo this procedure to determine where bleeding point is.

Pain management

In suspected HNC patients, the disease process can lead to unmanageable pain that can result in malnutrition[47] and negative psychological impact[48,49] leading to disengagement with service and treatments. It is imperative to assess and treat symptoms to prevent further deterioration of quality of life. Patients with HNC report a high prevalence of pain at 70%, with 48% of patients having pain as a presenting complaint.[50] Cancer pain can be classified into nociceptive or neuropathic pain and can arise from multiple etiologies such as tumor destruction of local tissues and nerves or because of previous treatments for example surgery or radiotherapy.[51] The World Health Organization (WHO) published updated guidelines on managing cancer pain in adults and adolescents in 2019 providing a framework for clinicians to manage cancer pain optimally.[52] Guiding principles can be adapted to managing patients with suspected head-and-neck pathology.

Pain management has shifted from general application of the WHO analgesic ladder to more individualized strategies considering patients' clinical situation, pain intensity, and availability of drugs.[53] Treatment of pain should be multi-modal and can be initiated with nonopioid analgesics such as nonsteroidal anti-inflammatory drugs as a monotherapy or in combination with weak and/or strong opioids for moderate-to-severe pain. Patients presenting with concomitant dysphagia might require alternatives to oral route such as intravenous and transdermal administration of pain medication.[54] Furthermore, patients can also present with neuropathic pain secondary to cranial nerve involvement, and these patients can benefit from neuropathic agents such as antidepressants[55,56] (tricyclic antidepressants) and anticonvulsants[57] (gabapentin). The summary of types of maintenance and adjuvant pharmacological treatment and typical starting dose are listed in Table 1.

Table 1.

Classes of medications and suggested recommended dose for managing pain in adults

Medicine group	Class	Examples
Nonopioids	Paracetamol NSAIDs	Tablets, liquid, rectal suppositories, injectable Ibuprofen - tablets, liquid Ketorolac - tablets, injectable
Opioids	Weak opioids Strong opioids	Codeine - oral tablets, liquid Morphine - tablets, liquid Fentanyl - injectable, transdermal patch, transmucosal lozenges
Adjuvants	Steroids Antidepressants Anticonvulsants	Dexamethasone - tablets, injectable Methylprednisolone - tablets, injectables Amitriptyline and venlafaxine - oral tablets Carbamazepine - oral tablets, injectables
Medicine	Typical starting dose	Notes
Paracetamol	500–1000 mg orally/intravenously every 6 h	Maximum of 4 g/24 h (in individuals with body weight>50 kg)
Ibuprofen	400–800 mg orally every 8 h	Take with food and/or protein pump inhibitor. Maximum dose 2.4 g/24 h
Morphine	5 mg orally every 4 h 2 mg intravenous/subcutaneous every 4 h	No maximum dose
Fentanyl	12–25 μg/h transdermal patch every 72 h	No maximum dose
Amitriptyline	10–25 mg orally at bedtime	Maximum dose 100 mg/24 h

Adapted from WHO. WHO: World Health Organization, NSAIDs: Nonsteroidal anti-inflammatory drugs

What recommendations should be given/referrals?

The NICE guidelines[58] recommend urgent referral when the patient suffers from persistent unexplained hoarseness, unexplained lump in the neck, persistent ulceration, a mass, or abnormal bleeding in the oral cavity, or a red and white patch in the oral cavity consistent with erythroplakia or erythroleukoplakia.

Increased awareness of the disease not only among patients but also clinicians is crucial for improving the rate of early diagnosis and therefore the survival outcomes.[59] So far, no strong evidence supports visual examination or other screening methods in the general population. There is no available screening for HNC or HPV, and HPV vaccination is not widely approved internationally for prevention of oropharyngeal cancer. However, it has gained the US Food and Drug Administration approval for prevention of oropharyngeal and other HNCs.[60] Evidence shows that the risk of HNC decreases with increasing time since smoking cessation.[61,62] Clinicians should be aware of associated risk factors of HNC, and information can be gathered through detailed history taking and to provide advice where appropriate to support primary prevention.

CONCLUSION

HNC can result in severe consequences when not recognized. Patients present with a myriad of symptoms possibly causing a delay in diagnosis. Emergency presentation is not infrequent and general practitioners and emergency doctors should be aware of the most common presenting symptoms and its appropriate management as described above. Special attention should be taken when patients present with a combination of the above-mentioned most common presenting symptoms.

Key points

• HNC presents with a variety of symptoms that can be seen in the emergency department and primary care

• Risk factors may not be obvious on presentation, but it is essential to be aware of them during initial assessment of patients

• The incidence of HPV-HNC is increasing modifying the paradigm of patients with HNC to younger and healthier individuals without the classic common risk factors

• Thorough history of presenting complaints, associated symptoms, chronicity, and systemic features is essential for diagnosis and management of the HNC

• Ventilation compromise might not be clinically obvious due to compensatory mechanisms, but airway obstruction secondary to HNC can result in rapid deterioration.

Research quality and ethics statement

The authors followed applicable EQUATOR Network (https://www.equator-network.org/) guidelines, notably the CARE guideline, during the conduct of this review.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.