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High-risk patients with a growing mass require proper assessment, including a thorough history, physical examination, and fine-needle aspiration for diagnosis.
A 65-year-old Vietnam veteran with a history of posttraumatic stress disorder (PTSD), transient ischemic attack, alcohol dependence, and a smoking history of 50 pack-years presents with a neck mass that has been growing for 2 months and unintentional weight loss of 25 pounds over 6 months. What is the differential diagnosis? How does a general practitioner evaluate, manage, and efficiently triage this patient?
Such cases, in which a head and neck cancer (HNC) diagnosis is suspected, can be unnerving for both physician and patient. However, knowledgeable general practitioners (GPs) can play a pivotal role in recognizing high-risk patients, initiating workups, and referring to appropriate specialists, resulting in earlier detection and potentially better outcomes.
This article outlines the authors’ recommended best practices for GPs treating patients with presumed HNC. Although the focus here is on the veteran population, in which HNC rates are significantly higher, many of the suggestions presented are applicable to the general population.
Background
Head and neck cancers represent a diverse family of malignancies of the nasopharynx, oropharynx, hypopharynx, larynx, oral cavity, paranasal sinuses, and salivary glands. This article does not cover thyroid, ophthalmologic, neurologic, or skin malignancies. The yearly worldwide incidence of all HNC cases is more than 550,000.1 In the U.S., 55,000 new HNC cases, representing 3% of all new malignancies, are reported annually. The 5-year survival rate is 60%, but 12,000 Americans die each year of head and neck cancer.2 Most HNCs occur in males aged ≥ 50 years, and the incidence increases with age. Almost $3.6 billion is spent treating HNC in the U.S. annually.3
Risk Factors
Alcohol and tobacco consumption strongly predisposes patients to squamous cell carcinoma (SCC), which accounts for 90% of HNCs. Together, alcohol and tobacco act multiplicatively.4,5 For instance, heavy drinkers (≥ 10 drinks daily) are at 5-fold increased risk for oral and pharyngeal cancers, heavy smokers (≥ 1 pack daily) are at 20-fold increased risk, and people who both drink and smoke heavily are at 50-fold increased risk.6 Head and neck cancer rates are significantly elevated even for moderate/light drinkers and smokers.
Veterans have disproportionately high rates of alcohol drinking and tobacco smoking,7,8 in part because these habits are ingrained in military culture. During World Wars I and II, tobacco companies supplied soldiers with daily rations of cigarettes,9 and advertisers targeted military personnel by linking smoking with patriotism, strength, and toughness.10 The VHA and the DoD reported that 33% of veterans and active-duty service personnel smoke—compared with 23% of civilians.11 Vietnam veterans, 47% of whom smoke, are at particular risk for HNC.12
Cessation of alcohol drinking and tobacco smoking is essential for overall prognosis, especially after HNC has been diagnosed. Continued smoking after HNC treatment increases the recurrence rate 4-fold.13 There also is mounting evidence that cessation of drinking and smoking can reverse the risk for HNC over time. According to a meta-analysis, quitting smoking for just 1 year begins to lower the risk for HNC. Quitting smoking for 20 years reduces the risk to the level of never smokers, and abstaining from alcohol for 20 years decreases the risk by nearly 40%.14
Viral infections are risk factors for development of oral cavity, oropharyngeal, laryngeal, and nasopharyngeal carcinoma (NPC). Sixty percent of oropharyngeal cancers are positive for human papillomavirus (HPV) infection,15 and most NPCs are associated with prior Epstein-Barr virus (EBV) exposure, particularly in populations from southern China, Southeast Asia, North Africa, and the Middle East.16
Evaluation
Workup of a possible HNC starts with taking a thorough history. Early HNC symptoms that may prompt a patient to seek medical care include neck mass, nonhealing oral ulcer, voice change, sore throat for more than 2 weeks, ear pain, nasal obstruction, serous otitis media, dysphagia, and odynophagia. Patients with advanced HNC may present with unintentional weight loss, decreased appetite, and cranial nerve deficits. For alcohol or tobacco users who present with any of the symptoms, SCC should lead the differential diagnosis, prompting examination of the head and neck. The authors present a general outline for performing this examination and detail the most common types of HNC encountered in the GP setting.
Physical Examination
The GP should perform a bimanual examination of the oral cavity, ears, nose, thyroid, and cranial nerve function with the help of a headlight. The physician should use 2 tongue blades to explore the oral cavity and palpate for suspicious oral lesions. It is often possible to feel a lesion before visualizing it on the base of the tongue. If there is a presenting mass, the physician should document the mass site, size, shape, consistency, tenderness, mobility, and accompanying deficits or symptoms.
Also recommended is a thorough examination of the facial, submandibular, and other cervical lymph nodes. The drainage patterns of these nodes can help the GP track potential routes of malignant infiltration. The submental and submandibular lymph nodes (level 1) drain the lower lip, floor of mouth, anterior tongue, and side of nose. The nodes along the mid and internal jugular vein (levels 2-4) and between the sternocleidomastoid and trapezius muscles (level 5) drain the oropharynx, mid tongue, larynx, hypopharynx, parotid gland, and skin of the face and ear. Nontender hard nodes are more likely to be malignant, as are nodes of the posterior triangle (level 5).17
Malignancy by Site
Oral cavity. The oral cavity includes the lips, buccal mucosa, teeth, gums, anterior two-thirds of tongue, floor of mouth, alveolar ridge, retromolar trigone, and hard palate. The oral cavity is the most common site for HNCs.18 The most common symptoms of malignancy of the oral cavity include dysphonia, nonhealing oral ulcers, loose teeth, bleeding, change in denture fit, and chin numbness, which could indicate mandibular invasion with inferior alveolar nerve involvement.19
For thorough assessment of the oral cavity, the patient should remove all temporary dental appliances. Then, with a tongue blade in each hand, the physician should thoroughly examine the oral mucosa, moving the tongue laterally to evaluate the floor of mouth, and palpate the mucosal surfaces to identify submucosal cancers in the posterior tongue and floor of mouth. Minor salivary glands are ubiquitous in the oral cavity and may be involved by cancer. Ulcerated painful lesions that last longer than 2 weeks are less likely to be common viral or aphthous ulcers. For either an oral cavity mass or a nonhealing ulcer that persists more than 4 weeks, malignancy should be suspected, and the patient should be referred for imaging and biopsy.
Leukoplakias are white patches in the oral cavity that develop from squamous epithelial hyperplasia and cannot be scraped away with a tonghpvue blade. The lesions are usually benign, but, if there is an element of redness (erythroplakia), the risk for harboring dysplasia is much higher, though the differential diagnosis includes trauma from adjacent teeth or lichen planus. If leukoplakia is seen, the physician should accurately note the size, location, and site and should monitor every 3 to 4 months. If erythroplakia, enlargement of leukoplakia, or any evidence of mucosal invasion is noted, the physician should refer to otolaryngologyhead and neck surgery (Oto-HNS). The authors advise against lasering leukoplakia; it is unnecessary, can make subsequent evaluation more difficult, and can mask recurrent malignancy.
Oropharynx. The oropharynx includes the posterior third of tongue, soft palate, palatine and lingual tonsils, and the posterior and lateral pharyngeal walls superior to tip of epiglottis. Cancers can arise in any of these locations and may present with dysphagia, odynophagia, referred
otalgia, hoarseness, and enlarged lymph nodes. In advanced cases, there may be bleeding, airway obstruction, and aspiration. Nonsmokers with oropharyngeal SCC are likely to be HPV positive and may be younger than the typical patient with alcohol- or tobacco-related HNC. Human papillomavirus positive oropharyngeal carcinoma has a much better prognosis than its tobaccorelated counterpart does. Physical examination should include assessment of tonsillar size and symmetry, palpation of neck lymph nodes, and palpation of base of tongue. Treatment may involve surgery, radiation, or chemoradiation, depending on factors such as extent of disease and comorbidities.
Nasopharynx. The nasopharynx extends from the nasal cavity (posterior to nasal septum) to the oropharynx. The most common NPC symptoms are middle-ear effusion and enlarged neck nodes. Nasal obstruction, epistaxis, or cranial nerve deficits also may occur. The nasopharynx
is best assessed with a fiberoptic scope. Most NPCs are associated with EBV infection, and viral levels can be used to monitor response to treatment.20 Early biopsy is indicated if a nasopharyngeal mass is found.
Larynx. As with the nasopharynx, the larynx is best seen with a fiberoptic scope. Malignancy generally presents with hoarseness, voice changes, cough, sore throat, or, if more advanced, airway compromise such as stridor and neck adenopathy. As larynx HNCs may be associated
with aspiration, the authors recommend asking “Does food go down the wrong pipe?” or “Do you cough when you eat?” and having the patient drink and document any difficulty. A smoker with hoarseness lasting more than 2 weeks should be referred to Oto-HNS for endoscopic assessment. Among veterans, other causes of hoarseness include polyps,Candida infection associated with inhalation of steroids for chronic obstructive pulmonary disease, and recurrent nerve paralysis from thyroid or lung cancer.
Neck. Patients with HNCs commonly present with a neck mass. Fifty percent to 80% of adults with a nontender neck mass are harboring a malignancy.21,22 In a patient without HIV, a neck mass larger than 2 cm should be evaluated for cancer, especially if the mass is hard and nontender.23 Computed tomography (CT) is recommended for initial evaluation, which, if there is FNA confirmed carcinoma, should be followed by positron emission tomography (PET). If there is concern for parotidor skull base tumors, magnetic resonance imaging (MRI) is preferable for demonstrating soft-tissue definition and disease extent.
If the patient is aged < 40 years and lymph nodes have been present for less than 2 to 4 weeks, are tender, or are associated with fever or poor dental hygiene, then an infection may instead be the cause. Dentistry referral and/or an antibiotic trial should be considered. Lymphomas, also common in the neck, may be accompanied by “B symptoms” (fever, night sweats, unintentional weight loss of > 10%).24 If lymphoma is suspected, fine-needle aspiration (FNA) for cytology and flow cytometry should be performed. If lymphoma is confirmed, the GP should refer the patient to an appropriate medical oncologist for further evaluation, which may include referral to Oto-HNS for core or open biopsy. Contraindications to FNA of a neck mass include paragangliomas, such as a carotid body tumor.
Other cancers of the upper aerodigestive tract also often spread to the neck nodes and may initially present as a neck mass. A thorough examination can usually point to the primary cancer, and FNA will provide the diagnosis with high specificity and sensitivity.25 Midline cystic neck masses in close proximity to the hyoid bone are likely thyroglossal duct cysts. If these cysts grow, they likely require removal.
Salivary glands. The submandibular, sublingual, and parotid are the major salivary glands. There also are hundreds of small salivary glands scattered through the oral and pharyngeal mucosa. Tumors arising from the salivary glands represent about 6% of all head and neck masses; these tumors are nearly 3 times more common in men than in women.26 About 80% of salivary gland tumors originate in the parotid gland; patients with such tumors typically present with a painless parotid mass.26 In advanced cases, patients may present with skin infiltration and facial paralysis secondary to involvement of
the facial nerve that courses through the parotid gland after it exits the temporal bone near the mastoid tip.
Salivary gland tumors are most commonly benign, and pleomorphic adenomas are the most common benign parotid neoplasm.27 The incidence of malignancy is highest in submandibular, sublingual, and minor salivary glands. There are numerous primary salivary gland malignancies, such as mucoepidermoid carcinoma, adenocarcinoma, and adenoid cystic carcinoma. Facial skin SCC may metastasize to periparotid nodes. There are also multiple nonneoplastic causes of salivary gland inflammation. Recurrent diffuse, painful gland enlargement may be suggestive of recurrent sialadenitis and may be
secondary to a stone or xerostomia associated with dehydration or use of diuretics, antidepressants, or lithium. Multiple lymphoepithelial cysts may be associated with HIV and do not require resection.28
Management
After taking a thorough history and performing a physical examination, the physician evaluating a patient for HNC should proceed with diagnostic testing followed by referral to a specialist.
Diagnostic Testing
Laboratory values. Although laboratory values are unlikely to help in evaluation of a malignancy, elevated white blood cell count, erythrocyte sedimentation
rate, and C-reactive protein level are markers of a general inflammatory process that may support a clinically suspected diagnosis of infection. Values that decrease over time may represent progress toward disease resolution.29
Imaging. If malignancy is suspected, imaging should be obtained. Imaging has an important role in corroborating examination findings of a mass. Imaging
also provides an accurate baseline assessment of tumor size and extent. Recommended imaging modalities include:
- Ultrasonography (US). This quick and inexpensive modality can be used to visualize suspicious neck lesions. It is helpful in performing real-time assessments and differentiating cysts from solid masses and abscesses from reactive lymph nodes or infiltrative tumors. Challenges with US include its inability to penetrate bone and practitioners’ variable interpretation of images. A different modality invariably is needed to document location and spread of suspected HNC.
- MRI and CT. These are necessary for HNC evaluation and staging. Generally, they are equivalent in node assessment, but MRI is preferable in tongue and pharynx evaluation, and CT is preferable in the larynx. An ideal image should extend from the skull base to the clavicles, demonstrating the extent of the primary tumor and potential metastases to the neck nodes. As MRI is best protocoled by an experienced head and neck radiologist, it is preferable to refer the patient to such a specialist and allow Oto-HNS to arrange the imaging. Contraindications to MRI include pacemakers and shrapnel (common among veteran patients) and claustrophobia (common among patients with PTSD).
- PET-CT. This modality helps in staging, detecting distant metastases, assessing treatment response after chemoradiation, and locating the primary cancer when a proven neck metastasis has no obvious source. Whether PET-CT should be performed before initial referral should be discussed with the specialist. A case with a proven distant metastasis likely is not operable and would be better served with a referral to medical oncology.
Biopsy. For almost all HNCs, the initial biopsy modality should be FNA. Although intraoral lesions may benefit from incisional biopsy, this procedure should not delay triage and may be outside the scope of practice for many GPs. A GP can arrange for FNA to be performed before the referral appointment. This modality has excellent diagnostic sensitivity and specificity.30,31 In the setting of equivocal or negative results despite a high index of suspicion, having a more experienced cytopathologist repeat the FNA is often warranted. Excisional biopsy may be warranted if FNA is nondiagnostic or lymphoma is diagnosed.
Other Interventions
In some cases, the GP has additional important roles— in preparing the patient for the possibility of surgery, treating related conditions, helping the patient cope with this new medical challenge, improving nutrition, and promoting cessation of alcohol drinking and tobacco smoking.
Surgery. For patients with biopsy-proven HNC, preoperative assessment by the GP helps provide clearance for surgery, reduces time to treatment, and lessens the likelihood of postoperative complications. A recent study found that VA patients aged ≥ 70 years had a 30-day postoperative mortality rate of 6% and at least a ≥ 20% risk for a major complication during their hospital stay.32 Given these risks and the overall higher rate of chronic diseases among veterans, the authors recommend preoperative evaluation of comorbidities with particular emphasis on cardiac, renal, and pulmonary status. In addition, specific examinations (eg, electrocardiogram, chest radiograph, basic laboratory tests, liver profile test) are recommended for patients with a history of alcohol abuse.
Malnutrition. At initial diagnosis, many patients with HNC have significant weight loss.33 Unfortunately, the required complex treatment modalities increase malnutrition rates and decrease quality of life.34 Preventive strategies are, therefore, key in improving patients’ overall health. The authors recommend that GPs consider early nutritional consultations and as-needed speech therapy evaluations to provide preventive strategies and exercises to maintain proper swallowing function.35 Patients who are unable to eat because of aspiration caused by a large tumor should be admitted for preoperative gastric tube placement to improve nutrition and, ultimately, surgical outcome. A large percentage of veterans with HNC also have depression, which may lead to decreased appetite.36 Mental health consultations can help in these circumstances, as can use of mirtazapine, which increases appetite and treats depression-related symptoms.
Pain. Nonsteroidal anti-inflammatory drugs (NSAIDs) can be recommended for relief of uncontrolled mild to moderate pain, but they must be discontinued 1 week before surgery to reduce the risk for bleeding complications. The NSAIDs should be avoided entirely in patients with untreated friable tumors of the aerodigestive tract. In patients with biopsy-proven cancer, pain control can involve opiates per World Health Organization guidelines.37 Patients with head and neck SCC often have neuropathic pain, which is more effectively treated with gabapentin.
Alcohol drinking and tobacco smoking. Promoting cessation of these habits is essential for all patients, including those already diagnosed with cancer. Encouraging cessation as well as overall healthy lifestyle choices can reduce cancer risk and improve overall health—and may be the single most efficacious intervention a physician can offer.
Referral
Most patients with suspected HNC should be referred to Oto-HNS. In cases in which lymphoma is most highly suspected, medical oncology is the most appropriate initial referral. Early dental consultation is also necessary if an obturator will be needed (eg, as with a hard palate malignancy) or if irradiation is planned (radiation-induced xerostomia significantly increases the risk for dental caries).38 For all new cancer diagnoses, the GP can contact the Oto-HNS specialist for help in tailoring the patient evaluation to the practices and resources at the GP’s home institution and reduce time to treatment.
Conclusion
General practitioners are essential in identifying and triaging veterans with HNC. High-risk patients with a growing mass require proper assessment, including a thorough history and physical examination, FNA for diagnosis, and appropriate specialist referral. Although this article provides a helpful framework for thinking about patients with HNC, the authors encourage GPs to check the National Comprehensive Cancer Network guidelines for additional information on the topics covered here. With this knowledge, GPs can improve outcomes for veterans with HNC.
Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.
Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.
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3. Mariotto 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(2): 117-128.
4. Davies L, Welch HG. Epidemiology of head and neck cancer in the United States. Otolaryngol Head Neck Surg. 2006;135(3):451-457.
5. Hashibe M, Brennan P, Chuang SC, et al. Interaction between tobacco and alcohol use and the risk of head and neck cancer: pooled analysis in the International Head and Neck Cancer Epidemiology Consortium. Cancer Epidemiol Biomarkers Prev. 2009;18(2):541-550.
6. Rodriguez T, Altieri A, Chatenoud L, et al. Risk factors for oral and pharyngeal cancer in young adults. Oral Oncol. 2004;40(2):207-213.
7. National Survey on Drug Use and Health. Alcohol Use and Alcohol-Related Risk Behaviors Among Veterans. NIH publication 99-4323. Rockville, MD: National Institutes of Health, U.S. Dept of Health and Human Services; 2005.
8. McKinney WP, McIntire DD, Carmody TJ, Joseph A. Comparing the smoking behavior of veterans and nonveterans. Public Health Rep. 1997;112(3):212-217.
9. Smith EA, Malone RE. “Everywhere the soldier will be”: wartime tobacco promotion in the US military. Am J Public Health. 2009;99(9):1595-1602.
10. James R, Olstad S. Cigarette advertising. Time. June 15, 2009.
11. Miller DR, Kalman D, Ren XS, Lee AF, Niu Z, Kazis LE. Health Behaviors of Veterans in the VHA: Tobacco Use: 1999 Large Health Survey of VHA Enrollees. Washington, DC: Office of Quality and Performance, Veterans Health Administration, U.S. Dept of Veterans Affairs; 2001.
12. Bray RM, Hourani LL, Rae Olmstead KL, et al. 2005 Department of Defense Survey of Health Related Behaviors Among Active Duty Military Personnel: A Component of the Defense Lifestyle Assessment Program (DLAP). Report prepared for U.S. Dept of Defense (Cooperative Agreement No. DAMD17-00-2-0057). Research Triangle Park, NC: RTI International; 2006.
13. Stevens MH, Gardner JW, Parkin JL, Johnson LP. Head and neck cancer survival and life-style change. Arch Otolaryngol. 1983;109(11):746-749.
14. Marron M, Boffetta P, Zhang ZF, et al. Cessation of alcohol drinking, tobacco smoking and the reversal of head and neck cancer risk. Int J Epidemiol. 2010;39(1):182-196.
15. Gillison ML. Human papillomavirus-associated head and neck cancer is a distinct epidemiologic, clinical, and molecular entity. Semin Oncol. 2004;31(6):744-754.
16. Pathmanathan R, Prasad U, Sadler R, Flynn K, Raab-Traub N. Clonal proliferations of cells infected with Epstein-Barr virus in preinvasive lesions related to nasopharyngeal carcinoma. N Engl J Med. 1995;333(11):693-698.
17. Bazemore AW, Smucker DR. Lymphadenopathy and malignancy. Am Fam Physician. 2002;66(11):2103-2110.
18. American Cancer Society. Oral cavity and oropharyngeal cancer. American Cancer Society website. http://www.cancer.org/acs/groups/cid/documents/webcontent/003128-pdf.pdf. Updated January 27, 2016. Accessed July 6, 2016.
19. Pandey M, Rao LP, Das SR, Mathews A, Chacko EM, Naik BR. Patterns of mandibular invasion in oral squamous cell carcinoma of the mandibular region. World J Surg Oncol. 2007;5:12.
20. Leung SF, Zee B, Ma BB, et al. Plasma Epstein-Barr viral deoxyribonucleic acid quantitation complements tumor-node-metastasis staging prognostication in nasopharyngeal carcinoma. J Clin Oncol. 2006;24(34):5414-5418.
21. Dickson PV, Davidoff AM. Malignant neoplasms of the head and neck. Semin Pediatr Surg. 2006;15(2):92-98.
22. Lefebvre JL, Coche-Dequeant B, Van JT, Buisset E, Adenis A. Cervical lymph nodes from an unknown primary tumor in 190 patients. Am J Surg. 1990;160(4):443-446.
23. Bhattacharyya N. Predictive factors for neoplasia and malignancy in a neck mass. Arch Otolaryngol Head Neck Surg. 1999;125(3):303-307.
24. Dailey SH, Sataloff RT. Lymphoma: an update on evolving trends in staging and management. Ear Nose Throat J. 2001;80(3):164-170.
25. Schwarz R, Chan NH, MacFarlane JK. Fine needle aspiration cytology in the evaluation of head and neck masses. Am J Surg. 1990;159(5):482-485.
26. Carvalho AL, Nishimoto IN, Califano JA, Kowalski LP. Trends in incidence and prognosis for head and neck cancer in the United States: a site-specific analysis of the SEER database. Int J Cancer. 2005;114(5):806-816.
27. Jones AV, Craig GT, Speight PM, Franklin CD. The range and demographics of salivary gland tumours diagnosed in a UK population. Oral Oncol. 2008;44(4):407-417.
28. Shebl FM, Bhatia K, Engels EA. Salivary gland and nasopharyngeal cancers in individuals with acquired immunodeficiency syndrome in United States. Int J Cancer. 2010;126(10):2503-2508.
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31. Liu ES, Bernstein JM, Sculerati N, Wu HC. Fine needle aspiration biopsy of pediatric head and neck masses. Int J Pediatr Otorhinolaryngol. 2001;60(2):135-140.
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33. Head BA, Heitz L, Keeney C, et al. The relationship between weight loss and health-related quality of life in persons treated for head and neck cancer. Support Care Cancer. 2011;19(10):1511-1518.
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High-risk patients with a growing mass require proper assessment, including a thorough history, physical examination, and fine-needle aspiration for diagnosis.
A 65-year-old Vietnam veteran with a history of posttraumatic stress disorder (PTSD), transient ischemic attack, alcohol dependence, and a smoking history of 50 pack-years presents with a neck mass that has been growing for 2 months and unintentional weight loss of 25 pounds over 6 months. What is the differential diagnosis? How does a general practitioner evaluate, manage, and efficiently triage this patient?
Such cases, in which a head and neck cancer (HNC) diagnosis is suspected, can be unnerving for both physician and patient. However, knowledgeable general practitioners (GPs) can play a pivotal role in recognizing high-risk patients, initiating workups, and referring to appropriate specialists, resulting in earlier detection and potentially better outcomes.
This article outlines the authors’ recommended best practices for GPs treating patients with presumed HNC. Although the focus here is on the veteran population, in which HNC rates are significantly higher, many of the suggestions presented are applicable to the general population.
Background
Head and neck cancers represent a diverse family of malignancies of the nasopharynx, oropharynx, hypopharynx, larynx, oral cavity, paranasal sinuses, and salivary glands. This article does not cover thyroid, ophthalmologic, neurologic, or skin malignancies. The yearly worldwide incidence of all HNC cases is more than 550,000.1 In the U.S., 55,000 new HNC cases, representing 3% of all new malignancies, are reported annually. The 5-year survival rate is 60%, but 12,000 Americans die each year of head and neck cancer.2 Most HNCs occur in males aged ≥ 50 years, and the incidence increases with age. Almost $3.6 billion is spent treating HNC in the U.S. annually.3
Risk Factors
Alcohol and tobacco consumption strongly predisposes patients to squamous cell carcinoma (SCC), which accounts for 90% of HNCs. Together, alcohol and tobacco act multiplicatively.4,5 For instance, heavy drinkers (≥ 10 drinks daily) are at 5-fold increased risk for oral and pharyngeal cancers, heavy smokers (≥ 1 pack daily) are at 20-fold increased risk, and people who both drink and smoke heavily are at 50-fold increased risk.6 Head and neck cancer rates are significantly elevated even for moderate/light drinkers and smokers.
Veterans have disproportionately high rates of alcohol drinking and tobacco smoking,7,8 in part because these habits are ingrained in military culture. During World Wars I and II, tobacco companies supplied soldiers with daily rations of cigarettes,9 and advertisers targeted military personnel by linking smoking with patriotism, strength, and toughness.10 The VHA and the DoD reported that 33% of veterans and active-duty service personnel smoke—compared with 23% of civilians.11 Vietnam veterans, 47% of whom smoke, are at particular risk for HNC.12
Cessation of alcohol drinking and tobacco smoking is essential for overall prognosis, especially after HNC has been diagnosed. Continued smoking after HNC treatment increases the recurrence rate 4-fold.13 There also is mounting evidence that cessation of drinking and smoking can reverse the risk for HNC over time. According to a meta-analysis, quitting smoking for just 1 year begins to lower the risk for HNC. Quitting smoking for 20 years reduces the risk to the level of never smokers, and abstaining from alcohol for 20 years decreases the risk by nearly 40%.14
Viral infections are risk factors for development of oral cavity, oropharyngeal, laryngeal, and nasopharyngeal carcinoma (NPC). Sixty percent of oropharyngeal cancers are positive for human papillomavirus (HPV) infection,15 and most NPCs are associated with prior Epstein-Barr virus (EBV) exposure, particularly in populations from southern China, Southeast Asia, North Africa, and the Middle East.16
Evaluation
Workup of a possible HNC starts with taking a thorough history. Early HNC symptoms that may prompt a patient to seek medical care include neck mass, nonhealing oral ulcer, voice change, sore throat for more than 2 weeks, ear pain, nasal obstruction, serous otitis media, dysphagia, and odynophagia. Patients with advanced HNC may present with unintentional weight loss, decreased appetite, and cranial nerve deficits. For alcohol or tobacco users who present with any of the symptoms, SCC should lead the differential diagnosis, prompting examination of the head and neck. The authors present a general outline for performing this examination and detail the most common types of HNC encountered in the GP setting.
Physical Examination
The GP should perform a bimanual examination of the oral cavity, ears, nose, thyroid, and cranial nerve function with the help of a headlight. The physician should use 2 tongue blades to explore the oral cavity and palpate for suspicious oral lesions. It is often possible to feel a lesion before visualizing it on the base of the tongue. If there is a presenting mass, the physician should document the mass site, size, shape, consistency, tenderness, mobility, and accompanying deficits or symptoms.
Also recommended is a thorough examination of the facial, submandibular, and other cervical lymph nodes. The drainage patterns of these nodes can help the GP track potential routes of malignant infiltration. The submental and submandibular lymph nodes (level 1) drain the lower lip, floor of mouth, anterior tongue, and side of nose. The nodes along the mid and internal jugular vein (levels 2-4) and between the sternocleidomastoid and trapezius muscles (level 5) drain the oropharynx, mid tongue, larynx, hypopharynx, parotid gland, and skin of the face and ear. Nontender hard nodes are more likely to be malignant, as are nodes of the posterior triangle (level 5).17
Malignancy by Site
Oral cavity. The oral cavity includes the lips, buccal mucosa, teeth, gums, anterior two-thirds of tongue, floor of mouth, alveolar ridge, retromolar trigone, and hard palate. The oral cavity is the most common site for HNCs.18 The most common symptoms of malignancy of the oral cavity include dysphonia, nonhealing oral ulcers, loose teeth, bleeding, change in denture fit, and chin numbness, which could indicate mandibular invasion with inferior alveolar nerve involvement.19
For thorough assessment of the oral cavity, the patient should remove all temporary dental appliances. Then, with a tongue blade in each hand, the physician should thoroughly examine the oral mucosa, moving the tongue laterally to evaluate the floor of mouth, and palpate the mucosal surfaces to identify submucosal cancers in the posterior tongue and floor of mouth. Minor salivary glands are ubiquitous in the oral cavity and may be involved by cancer. Ulcerated painful lesions that last longer than 2 weeks are less likely to be common viral or aphthous ulcers. For either an oral cavity mass or a nonhealing ulcer that persists more than 4 weeks, malignancy should be suspected, and the patient should be referred for imaging and biopsy.
Leukoplakias are white patches in the oral cavity that develop from squamous epithelial hyperplasia and cannot be scraped away with a tonghpvue blade. The lesions are usually benign, but, if there is an element of redness (erythroplakia), the risk for harboring dysplasia is much higher, though the differential diagnosis includes trauma from adjacent teeth or lichen planus. If leukoplakia is seen, the physician should accurately note the size, location, and site and should monitor every 3 to 4 months. If erythroplakia, enlargement of leukoplakia, or any evidence of mucosal invasion is noted, the physician should refer to otolaryngologyhead and neck surgery (Oto-HNS). The authors advise against lasering leukoplakia; it is unnecessary, can make subsequent evaluation more difficult, and can mask recurrent malignancy.
Oropharynx. The oropharynx includes the posterior third of tongue, soft palate, palatine and lingual tonsils, and the posterior and lateral pharyngeal walls superior to tip of epiglottis. Cancers can arise in any of these locations and may present with dysphagia, odynophagia, referred
otalgia, hoarseness, and enlarged lymph nodes. In advanced cases, there may be bleeding, airway obstruction, and aspiration. Nonsmokers with oropharyngeal SCC are likely to be HPV positive and may be younger than the typical patient with alcohol- or tobacco-related HNC. Human papillomavirus positive oropharyngeal carcinoma has a much better prognosis than its tobaccorelated counterpart does. Physical examination should include assessment of tonsillar size and symmetry, palpation of neck lymph nodes, and palpation of base of tongue. Treatment may involve surgery, radiation, or chemoradiation, depending on factors such as extent of disease and comorbidities.
Nasopharynx. The nasopharynx extends from the nasal cavity (posterior to nasal septum) to the oropharynx. The most common NPC symptoms are middle-ear effusion and enlarged neck nodes. Nasal obstruction, epistaxis, or cranial nerve deficits also may occur. The nasopharynx
is best assessed with a fiberoptic scope. Most NPCs are associated with EBV infection, and viral levels can be used to monitor response to treatment.20 Early biopsy is indicated if a nasopharyngeal mass is found.
Larynx. As with the nasopharynx, the larynx is best seen with a fiberoptic scope. Malignancy generally presents with hoarseness, voice changes, cough, sore throat, or, if more advanced, airway compromise such as stridor and neck adenopathy. As larynx HNCs may be associated
with aspiration, the authors recommend asking “Does food go down the wrong pipe?” or “Do you cough when you eat?” and having the patient drink and document any difficulty. A smoker with hoarseness lasting more than 2 weeks should be referred to Oto-HNS for endoscopic assessment. Among veterans, other causes of hoarseness include polyps,Candida infection associated with inhalation of steroids for chronic obstructive pulmonary disease, and recurrent nerve paralysis from thyroid or lung cancer.
Neck. Patients with HNCs commonly present with a neck mass. Fifty percent to 80% of adults with a nontender neck mass are harboring a malignancy.21,22 In a patient without HIV, a neck mass larger than 2 cm should be evaluated for cancer, especially if the mass is hard and nontender.23 Computed tomography (CT) is recommended for initial evaluation, which, if there is FNA confirmed carcinoma, should be followed by positron emission tomography (PET). If there is concern for parotidor skull base tumors, magnetic resonance imaging (MRI) is preferable for demonstrating soft-tissue definition and disease extent.
If the patient is aged < 40 years and lymph nodes have been present for less than 2 to 4 weeks, are tender, or are associated with fever or poor dental hygiene, then an infection may instead be the cause. Dentistry referral and/or an antibiotic trial should be considered. Lymphomas, also common in the neck, may be accompanied by “B symptoms” (fever, night sweats, unintentional weight loss of > 10%).24 If lymphoma is suspected, fine-needle aspiration (FNA) for cytology and flow cytometry should be performed. If lymphoma is confirmed, the GP should refer the patient to an appropriate medical oncologist for further evaluation, which may include referral to Oto-HNS for core or open biopsy. Contraindications to FNA of a neck mass include paragangliomas, such as a carotid body tumor.
Other cancers of the upper aerodigestive tract also often spread to the neck nodes and may initially present as a neck mass. A thorough examination can usually point to the primary cancer, and FNA will provide the diagnosis with high specificity and sensitivity.25 Midline cystic neck masses in close proximity to the hyoid bone are likely thyroglossal duct cysts. If these cysts grow, they likely require removal.
Salivary glands. The submandibular, sublingual, and parotid are the major salivary glands. There also are hundreds of small salivary glands scattered through the oral and pharyngeal mucosa. Tumors arising from the salivary glands represent about 6% of all head and neck masses; these tumors are nearly 3 times more common in men than in women.26 About 80% of salivary gland tumors originate in the parotid gland; patients with such tumors typically present with a painless parotid mass.26 In advanced cases, patients may present with skin infiltration and facial paralysis secondary to involvement of
the facial nerve that courses through the parotid gland after it exits the temporal bone near the mastoid tip.
Salivary gland tumors are most commonly benign, and pleomorphic adenomas are the most common benign parotid neoplasm.27 The incidence of malignancy is highest in submandibular, sublingual, and minor salivary glands. There are numerous primary salivary gland malignancies, such as mucoepidermoid carcinoma, adenocarcinoma, and adenoid cystic carcinoma. Facial skin SCC may metastasize to periparotid nodes. There are also multiple nonneoplastic causes of salivary gland inflammation. Recurrent diffuse, painful gland enlargement may be suggestive of recurrent sialadenitis and may be
secondary to a stone or xerostomia associated with dehydration or use of diuretics, antidepressants, or lithium. Multiple lymphoepithelial cysts may be associated with HIV and do not require resection.28
Management
After taking a thorough history and performing a physical examination, the physician evaluating a patient for HNC should proceed with diagnostic testing followed by referral to a specialist.
Diagnostic Testing
Laboratory values. Although laboratory values are unlikely to help in evaluation of a malignancy, elevated white blood cell count, erythrocyte sedimentation
rate, and C-reactive protein level are markers of a general inflammatory process that may support a clinically suspected diagnosis of infection. Values that decrease over time may represent progress toward disease resolution.29
Imaging. If malignancy is suspected, imaging should be obtained. Imaging has an important role in corroborating examination findings of a mass. Imaging
also provides an accurate baseline assessment of tumor size and extent. Recommended imaging modalities include:
- Ultrasonography (US). This quick and inexpensive modality can be used to visualize suspicious neck lesions. It is helpful in performing real-time assessments and differentiating cysts from solid masses and abscesses from reactive lymph nodes or infiltrative tumors. Challenges with US include its inability to penetrate bone and practitioners’ variable interpretation of images. A different modality invariably is needed to document location and spread of suspected HNC.
- MRI and CT. These are necessary for HNC evaluation and staging. Generally, they are equivalent in node assessment, but MRI is preferable in tongue and pharynx evaluation, and CT is preferable in the larynx. An ideal image should extend from the skull base to the clavicles, demonstrating the extent of the primary tumor and potential metastases to the neck nodes. As MRI is best protocoled by an experienced head and neck radiologist, it is preferable to refer the patient to such a specialist and allow Oto-HNS to arrange the imaging. Contraindications to MRI include pacemakers and shrapnel (common among veteran patients) and claustrophobia (common among patients with PTSD).
- PET-CT. This modality helps in staging, detecting distant metastases, assessing treatment response after chemoradiation, and locating the primary cancer when a proven neck metastasis has no obvious source. Whether PET-CT should be performed before initial referral should be discussed with the specialist. A case with a proven distant metastasis likely is not operable and would be better served with a referral to medical oncology.
Biopsy. For almost all HNCs, the initial biopsy modality should be FNA. Although intraoral lesions may benefit from incisional biopsy, this procedure should not delay triage and may be outside the scope of practice for many GPs. A GP can arrange for FNA to be performed before the referral appointment. This modality has excellent diagnostic sensitivity and specificity.30,31 In the setting of equivocal or negative results despite a high index of suspicion, having a more experienced cytopathologist repeat the FNA is often warranted. Excisional biopsy may be warranted if FNA is nondiagnostic or lymphoma is diagnosed.
Other Interventions
In some cases, the GP has additional important roles— in preparing the patient for the possibility of surgery, treating related conditions, helping the patient cope with this new medical challenge, improving nutrition, and promoting cessation of alcohol drinking and tobacco smoking.
Surgery. For patients with biopsy-proven HNC, preoperative assessment by the GP helps provide clearance for surgery, reduces time to treatment, and lessens the likelihood of postoperative complications. A recent study found that VA patients aged ≥ 70 years had a 30-day postoperative mortality rate of 6% and at least a ≥ 20% risk for a major complication during their hospital stay.32 Given these risks and the overall higher rate of chronic diseases among veterans, the authors recommend preoperative evaluation of comorbidities with particular emphasis on cardiac, renal, and pulmonary status. In addition, specific examinations (eg, electrocardiogram, chest radiograph, basic laboratory tests, liver profile test) are recommended for patients with a history of alcohol abuse.
Malnutrition. At initial diagnosis, many patients with HNC have significant weight loss.33 Unfortunately, the required complex treatment modalities increase malnutrition rates and decrease quality of life.34 Preventive strategies are, therefore, key in improving patients’ overall health. The authors recommend that GPs consider early nutritional consultations and as-needed speech therapy evaluations to provide preventive strategies and exercises to maintain proper swallowing function.35 Patients who are unable to eat because of aspiration caused by a large tumor should be admitted for preoperative gastric tube placement to improve nutrition and, ultimately, surgical outcome. A large percentage of veterans with HNC also have depression, which may lead to decreased appetite.36 Mental health consultations can help in these circumstances, as can use of mirtazapine, which increases appetite and treats depression-related symptoms.
Pain. Nonsteroidal anti-inflammatory drugs (NSAIDs) can be recommended for relief of uncontrolled mild to moderate pain, but they must be discontinued 1 week before surgery to reduce the risk for bleeding complications. The NSAIDs should be avoided entirely in patients with untreated friable tumors of the aerodigestive tract. In patients with biopsy-proven cancer, pain control can involve opiates per World Health Organization guidelines.37 Patients with head and neck SCC often have neuropathic pain, which is more effectively treated with gabapentin.
Alcohol drinking and tobacco smoking. Promoting cessation of these habits is essential for all patients, including those already diagnosed with cancer. Encouraging cessation as well as overall healthy lifestyle choices can reduce cancer risk and improve overall health—and may be the single most efficacious intervention a physician can offer.
Referral
Most patients with suspected HNC should be referred to Oto-HNS. In cases in which lymphoma is most highly suspected, medical oncology is the most appropriate initial referral. Early dental consultation is also necessary if an obturator will be needed (eg, as with a hard palate malignancy) or if irradiation is planned (radiation-induced xerostomia significantly increases the risk for dental caries).38 For all new cancer diagnoses, the GP can contact the Oto-HNS specialist for help in tailoring the patient evaluation to the practices and resources at the GP’s home institution and reduce time to treatment.
Conclusion
General practitioners are essential in identifying and triaging veterans with HNC. High-risk patients with a growing mass require proper assessment, including a thorough history and physical examination, FNA for diagnosis, and appropriate specialist referral. Although this article provides a helpful framework for thinking about patients with HNC, the authors encourage GPs to check the National Comprehensive Cancer Network guidelines for additional information on the topics covered here. With this knowledge, GPs can improve outcomes for veterans with HNC.
Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.
Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.
Click here to read the digital edition.
High-risk patients with a growing mass require proper assessment, including a thorough history, physical examination, and fine-needle aspiration for diagnosis.
A 65-year-old Vietnam veteran with a history of posttraumatic stress disorder (PTSD), transient ischemic attack, alcohol dependence, and a smoking history of 50 pack-years presents with a neck mass that has been growing for 2 months and unintentional weight loss of 25 pounds over 6 months. What is the differential diagnosis? How does a general practitioner evaluate, manage, and efficiently triage this patient?
Such cases, in which a head and neck cancer (HNC) diagnosis is suspected, can be unnerving for both physician and patient. However, knowledgeable general practitioners (GPs) can play a pivotal role in recognizing high-risk patients, initiating workups, and referring to appropriate specialists, resulting in earlier detection and potentially better outcomes.
This article outlines the authors’ recommended best practices for GPs treating patients with presumed HNC. Although the focus here is on the veteran population, in which HNC rates are significantly higher, many of the suggestions presented are applicable to the general population.
Background
Head and neck cancers represent a diverse family of malignancies of the nasopharynx, oropharynx, hypopharynx, larynx, oral cavity, paranasal sinuses, and salivary glands. This article does not cover thyroid, ophthalmologic, neurologic, or skin malignancies. The yearly worldwide incidence of all HNC cases is more than 550,000.1 In the U.S., 55,000 new HNC cases, representing 3% of all new malignancies, are reported annually. The 5-year survival rate is 60%, but 12,000 Americans die each year of head and neck cancer.2 Most HNCs occur in males aged ≥ 50 years, and the incidence increases with age. Almost $3.6 billion is spent treating HNC in the U.S. annually.3
Risk Factors
Alcohol and tobacco consumption strongly predisposes patients to squamous cell carcinoma (SCC), which accounts for 90% of HNCs. Together, alcohol and tobacco act multiplicatively.4,5 For instance, heavy drinkers (≥ 10 drinks daily) are at 5-fold increased risk for oral and pharyngeal cancers, heavy smokers (≥ 1 pack daily) are at 20-fold increased risk, and people who both drink and smoke heavily are at 50-fold increased risk.6 Head and neck cancer rates are significantly elevated even for moderate/light drinkers and smokers.
Veterans have disproportionately high rates of alcohol drinking and tobacco smoking,7,8 in part because these habits are ingrained in military culture. During World Wars I and II, tobacco companies supplied soldiers with daily rations of cigarettes,9 and advertisers targeted military personnel by linking smoking with patriotism, strength, and toughness.10 The VHA and the DoD reported that 33% of veterans and active-duty service personnel smoke—compared with 23% of civilians.11 Vietnam veterans, 47% of whom smoke, are at particular risk for HNC.12
Cessation of alcohol drinking and tobacco smoking is essential for overall prognosis, especially after HNC has been diagnosed. Continued smoking after HNC treatment increases the recurrence rate 4-fold.13 There also is mounting evidence that cessation of drinking and smoking can reverse the risk for HNC over time. According to a meta-analysis, quitting smoking for just 1 year begins to lower the risk for HNC. Quitting smoking for 20 years reduces the risk to the level of never smokers, and abstaining from alcohol for 20 years decreases the risk by nearly 40%.14
Viral infections are risk factors for development of oral cavity, oropharyngeal, laryngeal, and nasopharyngeal carcinoma (NPC). Sixty percent of oropharyngeal cancers are positive for human papillomavirus (HPV) infection,15 and most NPCs are associated with prior Epstein-Barr virus (EBV) exposure, particularly in populations from southern China, Southeast Asia, North Africa, and the Middle East.16
Evaluation
Workup of a possible HNC starts with taking a thorough history. Early HNC symptoms that may prompt a patient to seek medical care include neck mass, nonhealing oral ulcer, voice change, sore throat for more than 2 weeks, ear pain, nasal obstruction, serous otitis media, dysphagia, and odynophagia. Patients with advanced HNC may present with unintentional weight loss, decreased appetite, and cranial nerve deficits. For alcohol or tobacco users who present with any of the symptoms, SCC should lead the differential diagnosis, prompting examination of the head and neck. The authors present a general outline for performing this examination and detail the most common types of HNC encountered in the GP setting.
Physical Examination
The GP should perform a bimanual examination of the oral cavity, ears, nose, thyroid, and cranial nerve function with the help of a headlight. The physician should use 2 tongue blades to explore the oral cavity and palpate for suspicious oral lesions. It is often possible to feel a lesion before visualizing it on the base of the tongue. If there is a presenting mass, the physician should document the mass site, size, shape, consistency, tenderness, mobility, and accompanying deficits or symptoms.
Also recommended is a thorough examination of the facial, submandibular, and other cervical lymph nodes. The drainage patterns of these nodes can help the GP track potential routes of malignant infiltration. The submental and submandibular lymph nodes (level 1) drain the lower lip, floor of mouth, anterior tongue, and side of nose. The nodes along the mid and internal jugular vein (levels 2-4) and between the sternocleidomastoid and trapezius muscles (level 5) drain the oropharynx, mid tongue, larynx, hypopharynx, parotid gland, and skin of the face and ear. Nontender hard nodes are more likely to be malignant, as are nodes of the posterior triangle (level 5).17
Malignancy by Site
Oral cavity. The oral cavity includes the lips, buccal mucosa, teeth, gums, anterior two-thirds of tongue, floor of mouth, alveolar ridge, retromolar trigone, and hard palate. The oral cavity is the most common site for HNCs.18 The most common symptoms of malignancy of the oral cavity include dysphonia, nonhealing oral ulcers, loose teeth, bleeding, change in denture fit, and chin numbness, which could indicate mandibular invasion with inferior alveolar nerve involvement.19
For thorough assessment of the oral cavity, the patient should remove all temporary dental appliances. Then, with a tongue blade in each hand, the physician should thoroughly examine the oral mucosa, moving the tongue laterally to evaluate the floor of mouth, and palpate the mucosal surfaces to identify submucosal cancers in the posterior tongue and floor of mouth. Minor salivary glands are ubiquitous in the oral cavity and may be involved by cancer. Ulcerated painful lesions that last longer than 2 weeks are less likely to be common viral or aphthous ulcers. For either an oral cavity mass or a nonhealing ulcer that persists more than 4 weeks, malignancy should be suspected, and the patient should be referred for imaging and biopsy.
Leukoplakias are white patches in the oral cavity that develop from squamous epithelial hyperplasia and cannot be scraped away with a tonghpvue blade. The lesions are usually benign, but, if there is an element of redness (erythroplakia), the risk for harboring dysplasia is much higher, though the differential diagnosis includes trauma from adjacent teeth or lichen planus. If leukoplakia is seen, the physician should accurately note the size, location, and site and should monitor every 3 to 4 months. If erythroplakia, enlargement of leukoplakia, or any evidence of mucosal invasion is noted, the physician should refer to otolaryngologyhead and neck surgery (Oto-HNS). The authors advise against lasering leukoplakia; it is unnecessary, can make subsequent evaluation more difficult, and can mask recurrent malignancy.
Oropharynx. The oropharynx includes the posterior third of tongue, soft palate, palatine and lingual tonsils, and the posterior and lateral pharyngeal walls superior to tip of epiglottis. Cancers can arise in any of these locations and may present with dysphagia, odynophagia, referred
otalgia, hoarseness, and enlarged lymph nodes. In advanced cases, there may be bleeding, airway obstruction, and aspiration. Nonsmokers with oropharyngeal SCC are likely to be HPV positive and may be younger than the typical patient with alcohol- or tobacco-related HNC. Human papillomavirus positive oropharyngeal carcinoma has a much better prognosis than its tobaccorelated counterpart does. Physical examination should include assessment of tonsillar size and symmetry, palpation of neck lymph nodes, and palpation of base of tongue. Treatment may involve surgery, radiation, or chemoradiation, depending on factors such as extent of disease and comorbidities.
Nasopharynx. The nasopharynx extends from the nasal cavity (posterior to nasal septum) to the oropharynx. The most common NPC symptoms are middle-ear effusion and enlarged neck nodes. Nasal obstruction, epistaxis, or cranial nerve deficits also may occur. The nasopharynx
is best assessed with a fiberoptic scope. Most NPCs are associated with EBV infection, and viral levels can be used to monitor response to treatment.20 Early biopsy is indicated if a nasopharyngeal mass is found.
Larynx. As with the nasopharynx, the larynx is best seen with a fiberoptic scope. Malignancy generally presents with hoarseness, voice changes, cough, sore throat, or, if more advanced, airway compromise such as stridor and neck adenopathy. As larynx HNCs may be associated
with aspiration, the authors recommend asking “Does food go down the wrong pipe?” or “Do you cough when you eat?” and having the patient drink and document any difficulty. A smoker with hoarseness lasting more than 2 weeks should be referred to Oto-HNS for endoscopic assessment. Among veterans, other causes of hoarseness include polyps,Candida infection associated with inhalation of steroids for chronic obstructive pulmonary disease, and recurrent nerve paralysis from thyroid or lung cancer.
Neck. Patients with HNCs commonly present with a neck mass. Fifty percent to 80% of adults with a nontender neck mass are harboring a malignancy.21,22 In a patient without HIV, a neck mass larger than 2 cm should be evaluated for cancer, especially if the mass is hard and nontender.23 Computed tomography (CT) is recommended for initial evaluation, which, if there is FNA confirmed carcinoma, should be followed by positron emission tomography (PET). If there is concern for parotidor skull base tumors, magnetic resonance imaging (MRI) is preferable for demonstrating soft-tissue definition and disease extent.
If the patient is aged < 40 years and lymph nodes have been present for less than 2 to 4 weeks, are tender, or are associated with fever or poor dental hygiene, then an infection may instead be the cause. Dentistry referral and/or an antibiotic trial should be considered. Lymphomas, also common in the neck, may be accompanied by “B symptoms” (fever, night sweats, unintentional weight loss of > 10%).24 If lymphoma is suspected, fine-needle aspiration (FNA) for cytology and flow cytometry should be performed. If lymphoma is confirmed, the GP should refer the patient to an appropriate medical oncologist for further evaluation, which may include referral to Oto-HNS for core or open biopsy. Contraindications to FNA of a neck mass include paragangliomas, such as a carotid body tumor.
Other cancers of the upper aerodigestive tract also often spread to the neck nodes and may initially present as a neck mass. A thorough examination can usually point to the primary cancer, and FNA will provide the diagnosis with high specificity and sensitivity.25 Midline cystic neck masses in close proximity to the hyoid bone are likely thyroglossal duct cysts. If these cysts grow, they likely require removal.
Salivary glands. The submandibular, sublingual, and parotid are the major salivary glands. There also are hundreds of small salivary glands scattered through the oral and pharyngeal mucosa. Tumors arising from the salivary glands represent about 6% of all head and neck masses; these tumors are nearly 3 times more common in men than in women.26 About 80% of salivary gland tumors originate in the parotid gland; patients with such tumors typically present with a painless parotid mass.26 In advanced cases, patients may present with skin infiltration and facial paralysis secondary to involvement of
the facial nerve that courses through the parotid gland after it exits the temporal bone near the mastoid tip.
Salivary gland tumors are most commonly benign, and pleomorphic adenomas are the most common benign parotid neoplasm.27 The incidence of malignancy is highest in submandibular, sublingual, and minor salivary glands. There are numerous primary salivary gland malignancies, such as mucoepidermoid carcinoma, adenocarcinoma, and adenoid cystic carcinoma. Facial skin SCC may metastasize to periparotid nodes. There are also multiple nonneoplastic causes of salivary gland inflammation. Recurrent diffuse, painful gland enlargement may be suggestive of recurrent sialadenitis and may be
secondary to a stone or xerostomia associated with dehydration or use of diuretics, antidepressants, or lithium. Multiple lymphoepithelial cysts may be associated with HIV and do not require resection.28
Management
After taking a thorough history and performing a physical examination, the physician evaluating a patient for HNC should proceed with diagnostic testing followed by referral to a specialist.
Diagnostic Testing
Laboratory values. Although laboratory values are unlikely to help in evaluation of a malignancy, elevated white blood cell count, erythrocyte sedimentation
rate, and C-reactive protein level are markers of a general inflammatory process that may support a clinically suspected diagnosis of infection. Values that decrease over time may represent progress toward disease resolution.29
Imaging. If malignancy is suspected, imaging should be obtained. Imaging has an important role in corroborating examination findings of a mass. Imaging
also provides an accurate baseline assessment of tumor size and extent. Recommended imaging modalities include:
- Ultrasonography (US). This quick and inexpensive modality can be used to visualize suspicious neck lesions. It is helpful in performing real-time assessments and differentiating cysts from solid masses and abscesses from reactive lymph nodes or infiltrative tumors. Challenges with US include its inability to penetrate bone and practitioners’ variable interpretation of images. A different modality invariably is needed to document location and spread of suspected HNC.
- MRI and CT. These are necessary for HNC evaluation and staging. Generally, they are equivalent in node assessment, but MRI is preferable in tongue and pharynx evaluation, and CT is preferable in the larynx. An ideal image should extend from the skull base to the clavicles, demonstrating the extent of the primary tumor and potential metastases to the neck nodes. As MRI is best protocoled by an experienced head and neck radiologist, it is preferable to refer the patient to such a specialist and allow Oto-HNS to arrange the imaging. Contraindications to MRI include pacemakers and shrapnel (common among veteran patients) and claustrophobia (common among patients with PTSD).
- PET-CT. This modality helps in staging, detecting distant metastases, assessing treatment response after chemoradiation, and locating the primary cancer when a proven neck metastasis has no obvious source. Whether PET-CT should be performed before initial referral should be discussed with the specialist. A case with a proven distant metastasis likely is not operable and would be better served with a referral to medical oncology.
Biopsy. For almost all HNCs, the initial biopsy modality should be FNA. Although intraoral lesions may benefit from incisional biopsy, this procedure should not delay triage and may be outside the scope of practice for many GPs. A GP can arrange for FNA to be performed before the referral appointment. This modality has excellent diagnostic sensitivity and specificity.30,31 In the setting of equivocal or negative results despite a high index of suspicion, having a more experienced cytopathologist repeat the FNA is often warranted. Excisional biopsy may be warranted if FNA is nondiagnostic or lymphoma is diagnosed.
Other Interventions
In some cases, the GP has additional important roles— in preparing the patient for the possibility of surgery, treating related conditions, helping the patient cope with this new medical challenge, improving nutrition, and promoting cessation of alcohol drinking and tobacco smoking.
Surgery. For patients with biopsy-proven HNC, preoperative assessment by the GP helps provide clearance for surgery, reduces time to treatment, and lessens the likelihood of postoperative complications. A recent study found that VA patients aged ≥ 70 years had a 30-day postoperative mortality rate of 6% and at least a ≥ 20% risk for a major complication during their hospital stay.32 Given these risks and the overall higher rate of chronic diseases among veterans, the authors recommend preoperative evaluation of comorbidities with particular emphasis on cardiac, renal, and pulmonary status. In addition, specific examinations (eg, electrocardiogram, chest radiograph, basic laboratory tests, liver profile test) are recommended for patients with a history of alcohol abuse.
Malnutrition. At initial diagnosis, many patients with HNC have significant weight loss.33 Unfortunately, the required complex treatment modalities increase malnutrition rates and decrease quality of life.34 Preventive strategies are, therefore, key in improving patients’ overall health. The authors recommend that GPs consider early nutritional consultations and as-needed speech therapy evaluations to provide preventive strategies and exercises to maintain proper swallowing function.35 Patients who are unable to eat because of aspiration caused by a large tumor should be admitted for preoperative gastric tube placement to improve nutrition and, ultimately, surgical outcome. A large percentage of veterans with HNC also have depression, which may lead to decreased appetite.36 Mental health consultations can help in these circumstances, as can use of mirtazapine, which increases appetite and treats depression-related symptoms.
Pain. Nonsteroidal anti-inflammatory drugs (NSAIDs) can be recommended for relief of uncontrolled mild to moderate pain, but they must be discontinued 1 week before surgery to reduce the risk for bleeding complications. The NSAIDs should be avoided entirely in patients with untreated friable tumors of the aerodigestive tract. In patients with biopsy-proven cancer, pain control can involve opiates per World Health Organization guidelines.37 Patients with head and neck SCC often have neuropathic pain, which is more effectively treated with gabapentin.
Alcohol drinking and tobacco smoking. Promoting cessation of these habits is essential for all patients, including those already diagnosed with cancer. Encouraging cessation as well as overall healthy lifestyle choices can reduce cancer risk and improve overall health—and may be the single most efficacious intervention a physician can offer.
Referral
Most patients with suspected HNC should be referred to Oto-HNS. In cases in which lymphoma is most highly suspected, medical oncology is the most appropriate initial referral. Early dental consultation is also necessary if an obturator will be needed (eg, as with a hard palate malignancy) or if irradiation is planned (radiation-induced xerostomia significantly increases the risk for dental caries).38 For all new cancer diagnoses, the GP can contact the Oto-HNS specialist for help in tailoring the patient evaluation to the practices and resources at the GP’s home institution and reduce time to treatment.
Conclusion
General practitioners are essential in identifying and triaging veterans with HNC. High-risk patients with a growing mass require proper assessment, including a thorough history and physical examination, FNA for diagnosis, and appropriate specialist referral. Although this article provides a helpful framework for thinking about patients with HNC, the authors encourage GPs to check the National Comprehensive Cancer Network guidelines for additional information on the topics covered here. With this knowledge, GPs can improve outcomes for veterans with HNC.
Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.
Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.
Click here to read the digital edition.
1. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61(2):69-90.
2. Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin. 2014;64(1):9-29.
3. Mariotto 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(2): 117-128.
4. Davies L, Welch HG. Epidemiology of head and neck cancer in the United States. Otolaryngol Head Neck Surg. 2006;135(3):451-457.
5. Hashibe M, Brennan P, Chuang SC, et al. Interaction between tobacco and alcohol use and the risk of head and neck cancer: pooled analysis in the International Head and Neck Cancer Epidemiology Consortium. Cancer Epidemiol Biomarkers Prev. 2009;18(2):541-550.
6. Rodriguez T, Altieri A, Chatenoud L, et al. Risk factors for oral and pharyngeal cancer in young adults. Oral Oncol. 2004;40(2):207-213.
7. National Survey on Drug Use and Health. Alcohol Use and Alcohol-Related Risk Behaviors Among Veterans. NIH publication 99-4323. Rockville, MD: National Institutes of Health, U.S. Dept of Health and Human Services; 2005.
8. McKinney WP, McIntire DD, Carmody TJ, Joseph A. Comparing the smoking behavior of veterans and nonveterans. Public Health Rep. 1997;112(3):212-217.
9. Smith EA, Malone RE. “Everywhere the soldier will be”: wartime tobacco promotion in the US military. Am J Public Health. 2009;99(9):1595-1602.
10. James R, Olstad S. Cigarette advertising. Time. June 15, 2009.
11. Miller DR, Kalman D, Ren XS, Lee AF, Niu Z, Kazis LE. Health Behaviors of Veterans in the VHA: Tobacco Use: 1999 Large Health Survey of VHA Enrollees. Washington, DC: Office of Quality and Performance, Veterans Health Administration, U.S. Dept of Veterans Affairs; 2001.
12. Bray RM, Hourani LL, Rae Olmstead KL, et al. 2005 Department of Defense Survey of Health Related Behaviors Among Active Duty Military Personnel: A Component of the Defense Lifestyle Assessment Program (DLAP). Report prepared for U.S. Dept of Defense (Cooperative Agreement No. DAMD17-00-2-0057). Research Triangle Park, NC: RTI International; 2006.
13. Stevens MH, Gardner JW, Parkin JL, Johnson LP. Head and neck cancer survival and life-style change. Arch Otolaryngol. 1983;109(11):746-749.
14. Marron M, Boffetta P, Zhang ZF, et al. Cessation of alcohol drinking, tobacco smoking and the reversal of head and neck cancer risk. Int J Epidemiol. 2010;39(1):182-196.
15. Gillison ML. Human papillomavirus-associated head and neck cancer is a distinct epidemiologic, clinical, and molecular entity. Semin Oncol. 2004;31(6):744-754.
16. Pathmanathan R, Prasad U, Sadler R, Flynn K, Raab-Traub N. Clonal proliferations of cells infected with Epstein-Barr virus in preinvasive lesions related to nasopharyngeal carcinoma. N Engl J Med. 1995;333(11):693-698.
17. Bazemore AW, Smucker DR. Lymphadenopathy and malignancy. Am Fam Physician. 2002;66(11):2103-2110.
18. American Cancer Society. Oral cavity and oropharyngeal cancer. American Cancer Society website. http://www.cancer.org/acs/groups/cid/documents/webcontent/003128-pdf.pdf. Updated January 27, 2016. Accessed July 6, 2016.
19. Pandey M, Rao LP, Das SR, Mathews A, Chacko EM, Naik BR. Patterns of mandibular invasion in oral squamous cell carcinoma of the mandibular region. World J Surg Oncol. 2007;5:12.
20. Leung SF, Zee B, Ma BB, et al. Plasma Epstein-Barr viral deoxyribonucleic acid quantitation complements tumor-node-metastasis staging prognostication in nasopharyngeal carcinoma. J Clin Oncol. 2006;24(34):5414-5418.
21. Dickson PV, Davidoff AM. Malignant neoplasms of the head and neck. Semin Pediatr Surg. 2006;15(2):92-98.
22. Lefebvre JL, Coche-Dequeant B, Van JT, Buisset E, Adenis A. Cervical lymph nodes from an unknown primary tumor in 190 patients. Am J Surg. 1990;160(4):443-446.
23. Bhattacharyya N. Predictive factors for neoplasia and malignancy in a neck mass. Arch Otolaryngol Head Neck Surg. 1999;125(3):303-307.
24. Dailey SH, Sataloff RT. Lymphoma: an update on evolving trends in staging and management. Ear Nose Throat J. 2001;80(3):164-170.
25. Schwarz R, Chan NH, MacFarlane JK. Fine needle aspiration cytology in the evaluation of head and neck masses. Am J Surg. 1990;159(5):482-485.
26. Carvalho AL, Nishimoto IN, Califano JA, Kowalski LP. Trends in incidence and prognosis for head and neck cancer in the United States: a site-specific analysis of the SEER database. Int J Cancer. 2005;114(5):806-816.
27. Jones AV, Craig GT, Speight PM, Franklin CD. The range and demographics of salivary gland tumours diagnosed in a UK population. Oral Oncol. 2008;44(4):407-417.
28. Shebl FM, Bhatia K, Engels EA. Salivary gland and nasopharyngeal cancers in individuals with acquired immunodeficiency syndrome in United States. Int J Cancer. 2010;126(10):2503-2508.
29. Bien´ E, Balcerska A. Clinical significance of erythrocyte sedimentation rate, C-reactive protein and serum lactate dehydrogenase levels in the diagnosis, prognosis and treatment monitoring of children suffering from cancer [in Polish]. Med Wieku Rozwoj. 2004;8(4, pt 2):1081-1089.
30. Wu M, Burstein DE, Yuan S, et al. A comparative study of 200 fine needle aspiration biopsies performed by clinicians and cytopathologists. Laryngoscope. 2006;116(7):1212-1215.
31. Liu ES, Bernstein JM, Sculerati N, Wu HC. Fine needle aspiration biopsy of pediatric head and neck masses. Int J Pediatr Otorhinolaryngol. 2001;60(2):135-140.
32. Story DA. Postoperative complications in elderly patients and their significance for long-term prognosis. Curr Opin Anaesthesiol. 2008;21(3):375-379.
33. Head BA, Heitz L, Keeney C, et al. The relationship between weight loss and health-related quality of life in persons treated for head and neck cancer. Support Care Cancer. 2011;19(10):1511-1518.
34. van den Berg MG, Rasmussen-Conrad EL, van Nispen L, van Binsbergen JJ,
Merkx MA. A prospective study on malnutrition and quality of life in patients
with head and neck cancer. Oral Oncol. 2008;44(9):830-837.
35. Murphy BA, Deng J. Advances in supportive care for late effects of head and neck cancer. J Clin Oncol. 2015;33(29):3314-3321.
36. Pandey M, Devi N, Thomas BC, Kumar SV, Krishnan R, Ramdas K. Distress overlaps with anxiety and depression in patients with head and neck cancer. Psychooncology. 2007;16(6):582-586.
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15. Gillison ML. Human papillomavirus-associated head and neck cancer is a distinct epidemiologic, clinical, and molecular entity. Semin Oncol. 2004;31(6):744-754.
16. Pathmanathan R, Prasad U, Sadler R, Flynn K, Raab-Traub N. Clonal proliferations of cells infected with Epstein-Barr virus in preinvasive lesions related to nasopharyngeal carcinoma. N Engl J Med. 1995;333(11):693-698.
17. Bazemore AW, Smucker DR. Lymphadenopathy and malignancy. Am Fam Physician. 2002;66(11):2103-2110.
18. American Cancer Society. Oral cavity and oropharyngeal cancer. American Cancer Society website. http://www.cancer.org/acs/groups/cid/documents/webcontent/003128-pdf.pdf. Updated January 27, 2016. Accessed July 6, 2016.
19. Pandey M, Rao LP, Das SR, Mathews A, Chacko EM, Naik BR. Patterns of mandibular invasion in oral squamous cell carcinoma of the mandibular region. World J Surg Oncol. 2007;5:12.
20. Leung SF, Zee B, Ma BB, et al. Plasma Epstein-Barr viral deoxyribonucleic acid quantitation complements tumor-node-metastasis staging prognostication in nasopharyngeal carcinoma. J Clin Oncol. 2006;24(34):5414-5418.
21. Dickson PV, Davidoff AM. Malignant neoplasms of the head and neck. Semin Pediatr Surg. 2006;15(2):92-98.
22. Lefebvre JL, Coche-Dequeant B, Van JT, Buisset E, Adenis A. Cervical lymph nodes from an unknown primary tumor in 190 patients. Am J Surg. 1990;160(4):443-446.
23. Bhattacharyya N. Predictive factors for neoplasia and malignancy in a neck mass. Arch Otolaryngol Head Neck Surg. 1999;125(3):303-307.
24. Dailey SH, Sataloff RT. Lymphoma: an update on evolving trends in staging and management. Ear Nose Throat J. 2001;80(3):164-170.
25. Schwarz R, Chan NH, MacFarlane JK. Fine needle aspiration cytology in the evaluation of head and neck masses. Am J Surg. 1990;159(5):482-485.
26. Carvalho AL, Nishimoto IN, Califano JA, Kowalski LP. Trends in incidence and prognosis for head and neck cancer in the United States: a site-specific analysis of the SEER database. Int J Cancer. 2005;114(5):806-816.
27. Jones AV, Craig GT, Speight PM, Franklin CD. The range and demographics of salivary gland tumours diagnosed in a UK population. Oral Oncol. 2008;44(4):407-417.
28. Shebl FM, Bhatia K, Engels EA. Salivary gland and nasopharyngeal cancers in individuals with acquired immunodeficiency syndrome in United States. Int J Cancer. 2010;126(10):2503-2508.
29. Bien´ E, Balcerska A. Clinical significance of erythrocyte sedimentation rate, C-reactive protein and serum lactate dehydrogenase levels in the diagnosis, prognosis and treatment monitoring of children suffering from cancer [in Polish]. Med Wieku Rozwoj. 2004;8(4, pt 2):1081-1089.
30. Wu M, Burstein DE, Yuan S, et al. A comparative study of 200 fine needle aspiration biopsies performed by clinicians and cytopathologists. Laryngoscope. 2006;116(7):1212-1215.
31. Liu ES, Bernstein JM, Sculerati N, Wu HC. Fine needle aspiration biopsy of pediatric head and neck masses. Int J Pediatr Otorhinolaryngol. 2001;60(2):135-140.
32. Story DA. Postoperative complications in elderly patients and their significance for long-term prognosis. Curr Opin Anaesthesiol. 2008;21(3):375-379.
33. Head BA, Heitz L, Keeney C, et al. The relationship between weight loss and health-related quality of life in persons treated for head and neck cancer. Support Care Cancer. 2011;19(10):1511-1518.
34. van den Berg MG, Rasmussen-Conrad EL, van Nispen L, van Binsbergen JJ,
Merkx MA. A prospective study on malnutrition and quality of life in patients
with head and neck cancer. Oral Oncol. 2008;44(9):830-837.
35. Murphy BA, Deng J. Advances in supportive care for late effects of head and neck cancer. J Clin Oncol. 2015;33(29):3314-3321.
36. Pandey M, Devi N, Thomas BC, Kumar SV, Krishnan R, Ramdas K. Distress overlaps with anxiety and depression in patients with head and neck cancer. Psychooncology. 2007;16(6):582-586.
37. World Health Organization. Cancer Pain Relief: With a Guide to Opioid Availability.
2nd ed. Geneva, Switzerland: World Health Organization; 1996.
38. Epstein JB, Thariat J, Bensadoun RJ, et al. Oral complications of cancer and cancer
therapy: from cancer treatment to survivorship. CA Cancer J Clin. 2012;62(6):400-422.