Laryngeal Cancer

Sheila O. Stille, DMD, MAGD and Hugh J. Silk, MD, MPH, FAAFP Reviewed 06/2017
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Subject: Laryngeal Cancer

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BASICS

DESCRIPTION

  • A friable, granular tumor of the larynx that leads to hoarseness, hemoptysis, and cough

  • 2–5% of all malignant tumors; squamous cell carcinomas

  • System(s) affected: pulmonary; ear, nose, throat (ENT)

  • Synonym(s): cancer of the larynx; throat cancer; cancer of the voice box

EPIDEMIOLOGY

INCIDENCE

  • Per year, 3.2/100,000 (13,430 new cases per year in the United States, 2016) (1)[A]

  • Second most common cancer of aerodigestive tract (2)[A]

  • 85–90% of laryngeal cancers are squamous cell (2)[A].

  • Laryngeal cancer represents 0.8% of all new cases of cancer in the United States (1)[A].

  • ~60% of the cases present in advanced stages (III, IV).

  • 5-year survival rate 63%

  • Predominant age

    • Median age at diagnosis is 65 years; most frequently diagnosed between 50 and 70 years of age (3)[A]

    • <1% of laryngeal cancers arise in patients <30 years.

  • Predominant sex: male > female (5:1); blacks > whites (1)[A]; blacks diagnosed younger and higher death rate (2)[A]

PREVALENCE

  • 3,620 people dying from laryngeal cancer in 2016 in United States (1)[A]

  • Second most common site for head and neck cancer

  • 11th most common cancer in men (4)[C]

ETIOLOGY

  • Smoking tobacco (dose dependent) is the most significant risk factor (1)[A] linear association:

    • 30 times greater risk for heavy smoker

  • Heavy alcohol use, 8 or more drinks per day (1,3)[A]

  • Smoking plus moderate alcohol use—synergistic (1)[A]

  • Smoking cannabis (5)[B]

  • Possibly chronic gastroesophageal and laryngopharyngeal reflux (1,2)[A]

  • Occupational hazards (asbestos, pesticides, polycyclic aromatic hydrocarbons, textile dust, exposure to radiation) (1,3)[A]

  • Dietary—too much red meats have been suggested (1)[A]

  • Viruses, e.g., HPV/p16, prevalence ranges from 20% to 30% in laryngeal cancer with prognostic value unknown (1)[A].

GENETICS

Unknown—possible genetic inheritance 

RISK FACTORS

See “Etiology and Pathophysiology.” 

GENERAL PREVENTION

  • Avoid or cease smoking and/or alcohol abuse (85% attributed to smoking and alcohol abuse) (1)[A].

  • Wear proper respiratory masks/respirators if chronic exposure to certain chemicals, gases, and wood dust.

  • Control chronic laryngopharyngeal reflux.

  • Indirect laryngoscopy for at-risk patients with persistent hoarseness lasting >2 to 3 weeks

  • High intake of natural β-carotenoid equivalents may reduce risk of developing laryngeal cancer (6)[A].

  • HPV vaccination: Cost-effectiveness specifically for laryngeal cancer is unclear.

  • Prevention of second primary head and neck cancer with isotretinoin (3)[A].

  • Diet high in fruits and vegetables (1)[A].

ASSOCIATED CONDITIONS

Up to 10% of patients may have a synchronous squamous cell carcinoma in the lower or upper aerodigestive tract, most notably in the esophagus or lungs. 

DIAGNOSIS

  • Early laryngeal cancer generally has a good prognosis, with a 5-year disease-specific survival rate of >90% for T1 tumors (1)[A].

  • 55% are diagnosed at the localized stage (1)[A].

HISTORY

  • Hoarseness, dysphonia, in an elderly or middle-aged cigarette smoker, lasting >3 weeks (1,3)[A]

  • Sore throat, dysphagia, or odynophagia, lasting >6 weeks

  • Lump in neck

  • Swallowing dysfunction

  • Dyspnea and/or stridor

  • Ipsilateral otalgia

  • Chronic cough

  • Hemoptysis

  • Weight loss due to poor nutrition

  • Chronic exposure to known risk factors (see “Etiology and Pathophysiology”)

  • History of prior head and neck malignancy (4)[C]

PHYSICAL EXAM

  • Visualization of larynx initially by mirror and then a full nasolaryngoscopic exam (1)[A]

  • Physical observation of vocal cord mobility, airway patency (including lung auscultation), and any regional spread

  • Cervical lymph node exam and cranial nerve exam

  • Mass in the neck from metastatic lymph node

  • Broadening of the larynx on palpation with loss of crepitation

  • Fullness of the cricothyroid membrane

DIFFERENTIAL DIAGNOSIS

  • Acute or chronic laryngitis secondary to allergies, voice overuse, or chemical exposures

  • Benign vocal cord lesions such as polyps, nodules, and papillomas

INITIAL TESTS

  • Endoscopy

  • CT or MRI (CT: higher Sp, lower Se vs. MRI, but, both accurate 75–80% vs. 80–85%) (1)[A]

  • Barium swallow

  • Chest radiograph and liver function tests (LFT) with ultrasound (US) if metastasis suspected (most common sites of metastasis: lung > liver) (4)[C]

  • Bone scan if bone metastasis suspected

  • Pulmonary function tests: influences strategy and success of conservation surgical therapy (4)[A]

  • Blood work: chemistry (particularly BUN, Cr), LFT, and CBC, regardless of treatment strategy

DIAGNOSTIC PROCEDURES/SURGERY

Indirect and/or direct laryngoscopy and fine needle aspiration biopsy to determine stage of disease as well as histologic confirmation (1)[A

INTERPRETATION

Laryngoscopy: fungating, friable tumor with heaped-up edges and granular appearance, with multiple areas of central necrosis and exudate surrounding areas of hyperemia 

TREATMENT

  • Early laryngeal cancer (e.g., stage I or II) is often treated with single-modality therapy (1)[A]. No difference in overall survival between radiation therapy (XRT), open surgery, and endoscopic surgery (1)[A]

  • Increased use of endolaryngeal surgery (transoral endoscopic) with or without laser with similar survival rates as XRT and open surgery (1)[A],(4)[B]

  • Advantage of endolaryngeal surgery is voice and laryngeal function preservation compared to open and shorter treatment course compared to XRT. Voice preservation outcomes similar between endolaryngeal surgery and XRT (1)[A],(4)[B]

  • Transoral endoscopic surgery with laser leaves option open for XRT if recurrence, before going to open surgery (1)[A],(4)[B]

  • XRT and/or surgery, including laser excision surgery, is designed with preserving vocal function (7)[A].

  • Advanced laryngeal cancer (stage III or IV) is increasingly treated with chemoradiation therapy (combination of chemotherapy and XRT) (7)[A].

  • Disadvantages of XRT include prolonged course of treatment, and treatment of recurrence is limited to open surgery.

  • Multidisciplinary group needed to treat laryngeal cancer patients: head and neck surgeons, radiation oncologists, medical oncologists, head and neck radiologists, dentists, nutritionists, psychologists, and speech pathologists (1)[A].

GENERAL MEASURES

  • Tracheotomy care, when applicable

  • If patient is diagnosed during pregnancy: Natural history of disease and treatment side effects have to be weighed against the possibilities of continuing on to delivery.

MEDICATION

Opioids may be necessary for pain control during treatment for mucositis (of the mouth) secondary to RT. Limit opioid dosing and duration as able to prevent dependency. Swishing, gargling, and spitting with viscous lidocaine can be helpful as well. 

ISSUES FOR REFERRAL

  • ENT for direct visualization of larynx; biopsy and surgery

  • Depending on patient’s management plan, nutritional and dental consultations are needed. The latter is essential before treatment to reduce oral complications of treatment.

  • Treatment may result in need for voice rehabilitation and be the cause of social isolation, job loss, and depression; therefore, referrals to speech therapist, psychologist, social worker, and/or support groups as indicated.

ADDITIONAL THERAPIES

Radiotherapy 
  • There is increased focus on XRT, combined chemotherapy and XRT, and function-preserving laryngectomy surgery due to patient fear of voice loss (1)[A].

  • Early disease may be treatable by either XRT or laser cordectomy on an outpatient basis. If laser used first, leaves option of using XRT before going to open surgery.

SURGERY

  • Tracheotomy may be necessary if a tumor is large enough to cause upper airway obstruction.

  • More advanced disease needs inpatient care, necessitating partial or total laryngectomy and postoperative XRT 4 to 5 weeks after surgery depending on the stage of disease (2)[A].

INPATIENT CONSIDERATIONS

  • More advanced disease, surgical intervention, and complication management

  • Nutritional or airway issues/complications

  • Primarily outpatient care

ONGOING CARE

FOLLOWUP RECOMMENDATIONS

Patient may remain fully active unless debilitated from more advanced disease and/or greater degree of surgery. 
Reasons for posttreatment follow up: 
  • Evaluation of treatment response

  • Early identification of recurrence

  • Early detection of new primary tumors

  • Monitoring and management of complications

  • Optimization of rehabilitation

  • Promotion and maintenance of smoking and excessive alcohol cessation

  • Provision of support to patients and their families

  • Patient counselling and education

MONITORING

  • Complete otolaryngologic exam bimonthly for at least the first 2 years after primary treatment, when the recurrence rate is the highest, then every 6 months for minimum of 5 years (3)[A].

  • Repeat indirect laryngoscopy and complete head and neck exams at 3 months and then 6 month intervals for a minimum of 5 years after treatment to detect early recurrence or second primary. Second primary tumors reported in 25% of patients (3)[A]

  • Yearly chest x-rays and LFT monitoring for metastatic disease

  • Posttreatment surveillance for recurrence with PET/CT at 3 months and then at any suspicion of recurrence; can be better than traditional CT and/or MRI alone due to anatomic changes from treatment (1,3)[A]

  • Patients with dysphagia should undergo barium swallow and/or esophageal endoscopy to rule out second synchronous tumor in the esophagus.

  • Patients with unexplained pain should have appropriate radiologic or nuclear medicine bone scans (3)[A].

  • Mental status change warrants CT scan of the brain to rule out brain metastases.

DIET

  • Nasogastric or gastrostomy feeding may be necessary if tumor involves esophageal inlet.

  • No special diet otherwise

PATIENT TEACHING

PROGNOSIS

  • Early disease is expected to have 75–95% cure rate (depending on site, size, and depth of tumor invasion) (1)[A].

  • Most recurrences occur within 2 years of initial treatment (3)[A].

  • Mortality rate 1.1/100,000 per year in 2008 to 2012. (1)[A]. Death rates have been decreasing for oral and pharyngeal cancers over the last 3 decades, in part due to the decreasing rates of smoking (3)[A].

COMPLICATIONS

  • Temporary odynophagia or dysphagia secondary to mucositis and/or thrush during XRT

  • Radiation skin burns, xerostomia with XRT

  • Persistent hoarseness despite adequate treatment, necessitating further adjunctive procedures and/or speech therapy

  • Psychosocial stressors due to limitations in voice and laryngeal function (maintaining employment, general communication, etc.)

  • Tracheostoma stenosis requiring stenting with laryngectomy tubes or further surgery

  • Dysphagia secondary to upper esophageal stricture after total laryngectomy, necessitating dilation

  • Aspiration after partial laryngectomy, necessitating complete laryngectomy or tracheotomy

  • Radiation-induced chondronecrosis, which mimics tumor recurrence

  • Radiation-induced neoplasms

  • Radiation edema, necessitating emergent tracheotomy

  • Hypothyroidism secondary to laryngectomy and XRT (7)[A]

REFERENCES

Steuer CE, El-Deiry M, Parks JR et al. An update on larynx cancer [published online ahead of print November 29, 2016]. CA Cancer J Clin.  [View Abstract]
Zhang D, Zhou J, Chen B et al. Gastroesophageal reflux and carcinoma of larynx or pharynx: a meta-analysis. Acta Otolaryngol.  2014;134(10):982–989.  [View Abstract]
Simo R, Bradley P, Chevalier D et al. European Laryngological Society: ELS recommendations for the follow-up of patients treated for laryngeal cancer. Eur Arch Otorhinolaryngol.  2014;271(9):2469–2479.  [View Abstract]
Gun R, Ozer E. Surgical anatomy of oropharynx and supraglottic larynx for transoral robotic surgery. J Surg Oncol.  2015;112(7):690–696.  [View Abstract]
Bhattacharyya S, Mandal S, Banerjee S et al. Cannabis smoke can be a major risk factor for early-age laryngeal cancer—a molecular signaling-based approach. Tumour Biol.  2015;36(8):6029–6036.  [View Abstract]
Leoncini E, Nedovic D, Panic N et al. Carotenoid intake from natural sources and head and neck cancer: a systematic review and meta-analysis of epidemiological studies. Cancer Epidemiol Biomarkers Prev.  2015;24(7):1003–1011.  [View Abstract]
Luo XN, Chen LS, Zhang SY et al. Effectiveness of chemotherapy and radiotherapy for laryngeal preservation in advanced laryngeal cancer: a meta-analysis and systematic review. Radiol Med.  2015;120(12):1153–1169.  [View Abstract]

ADDITIONAL READING

  • D’Cruz AK, Sharma S, Pai PS. Current status of near-total laryngectomy: review. J Laryngol Otol.  2012;126(6):556–562.  [View Abstract]

  • Huang SH, Lockwood G, Irish J et al. Truths and myths about radiotherapy for verrucous carcinoma of larynx. Int J Radiat Oncol Biol Phys.  2009;73(4):1110–1115.  [View Abstract]

  • Hutcheson KA, Lewin JS. Functional outcomes after chemoradiotherapy of laryngeal and pharyngeal cancers. Curr Oncol Rep.  2012;14(2):158–165.  [View Abstract]

  • Misono S, Marmor S, Yueh B et al. T1 glottic carcinoma: do comorbidities, facility characteristics, and sociodemographics explain survival differences across treatment? Otolaryngol Head Neck Surg.  2015;152(5):856–862.  [View Abstract]

  • Pfister DG, Laurie SA, Weinstein GS et al. American Society of Clinical Oncology clinical practice guideline for the use of larynx-preservation strategies in the treatment of laryngeal cancer. J Clin Oncol.  2006;24(22):3693–3704.  [View Abstract]

CODES

ICD10

  • C32.9 Malignant neoplasm of larynx, unspecified

  • C32.8 Malignant neoplasm of overlapping sites of larynx

  • C32.3 Malignant neoplasm of laryngeal cartilage

  • C32.0 Malignant neoplasm of glottis

  • C32.1 Malignant neoplasm of supraglottis

  • C32.2 Malignant neoplasm of subglottis

ICD9

  • 161.9 Malignant neoplasm of larynx, unspecified

  • 161.8 Malignant neoplasm of other specified sites of larynx

  • 161.3 Malignant neoplasm of laryngeal cartilages

  • 161.0 Malignant neoplasm of glottis

  • 161.1 Malignant neoplasm of supraglottis

  • 161.2 Malignant neoplasm of subglottis

SNOMED

  • 363429002 Malignant tumor of larynx (disorder)

  • 371995001 Primary malignant neoplasm of larynx

  • 109370001 Primary malignant neoplasm of laryngeal cartilage

  • 93816002 Primary malignant neoplasm of glottis

  • 94080006 Primary malignant neoplasm of supraglottis

  • 94075002 Primary malignant neoplasm of subglottis

PEARLS

  • Persistent hoarseness in an at-risk older person should prompt investigation with indirect and/or direct laryngoscopy.

  • RT and multimodal therapies have reduced the need for laryngectomy except in advanced cases. ENT and radiation oncology consultations are recommended.

  • Counsel all patients about primary prevention (no smoking, limit alcohol use), and counsel patients with cancer on secondary prevention.

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