BASICS
DESCRIPTION
- A friable, granular tumor of the larynx that leads to hoarseness, hemoptysis, and cough
- Of all malignant lesions, <1% squamous cell carcinomas constitute 95 " ô98% of all malignant neoplasms of the larynx.
- 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 (13,560 new cases per year in the United States, 2015; prevalence: 88,852 in 2012); predominately squamous cell carcinomas (1)[A]
- Laryngeal cancer represents 0.8% of all new cases of cancer in the United States (1)[A].
- Predominant age
- Median age at diagnosis is 65 years; most frequently diagnosed between 55 and 64 years of age
- <1% of laryngeal cancers arise in patients <30 years.
- Predominant sex: male > female (5:1); blacks > whites (1,2)[A]; synergistic with alcohol abuse (2)[A]
Prevalence
- About 3,610 deaths from disease in the United States yearly (2)[A]
- Second most common site for head and neck cancer
- 11th most common cancer in men (3)[C]
ETIOLOGY AND PATHOPHYSIOLOGY
- Smoking tobacco (dose dependent) " ömost important risk factor (4)[C],(5)[B],(6)[A]
- Smoking cannabis (7)[B]
- Heavy alcohol use (4,8)[A]
- Smoking plus moderate alcohol use " ösynergistic (4)[C]
- Possibly chronic laryngopharyngeal reflux (small studies (9)[B])
- Occupational hazards (asbestos, pesticides, polycyclic aromatic hydrocarbons, woodworkers, exposure to radiation) (1,2)[A],(3)[C],(10)[A]
- Viruses, for example, HPV (< oropharyngeal; 35% vs. 24%) (11,12 and 13)[A]
Genetics
Unknown " öpossible genetic inheritance é á
RISK FACTORS
See "Etiology and Pathophysiology. " Ł é á
GENERAL PREVENTION
- Avoid or cease smoking and/or alcohol abuse (85% attributed to smoking and alcohol abuse (3)[C]).
- Wear proper respiratory masks/respirators if chronic exposure to certain chemicals, gases, and wood dust.
- Treat chronic laryngopharyngeal reflux.
- Indirect laryngoscopy for at-risk patients with persistent hoarseness lasting >2 to 3 weeks
- High intake of natural Ä ▓-carotenoid equivalents may reduce risk of developing laryngeal cancer (14)[A].
- HPV vaccination: Cost-effectiveness specifically for laryngeal cancer is unclear.
- Prevention of second primary head and neck cancer with isotretinoin (15)[A].
COMMONLY 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. é á
DIAGNOSIS
- Early laryngeal cancer generally has a good prognosis, with a 5-year disease-specific survival rate of >90% for T1 tumors (6)[A].
- 55% are diagnosed at the localized stage (1)[A].
HISTORY
- Persistent hoarseness or voice change in an elderly or middle-aged cigarette smoker, lasting >3 weeks (3)[C]
- Sore throat, dysphagia, or odynophagia, lasting >6 weeks
- Lump in neck
- 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 " Ł)
- History of prior head and neck malignancy (3)[C]
PHYSICAL EXAM
- Visualization of larynx initially by mirror and then a full nasolaryngoscopic exam (3)[C]
- 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
DIAGNOSTIC TESTS & INTERPRETATION
Initial Tests (lab, imaging)
- Endoscopy
- CT or MRI (CT: higher Sp, lower Se vs. MRI, but, both accurate 75 " ô80% vs. 80 " ô85%) (3)[C]
- Barium swallow
- Chest radiograph and liver function tests (LFT) with ultrasound (US) if metastasis suspected (most common sites of metastasis: lung > liver) (3)[C]
- Bone scan if bone metastasis suspected
- Pulmonary function tests: influences strategy and success of conservation surgical therapy (3)[A]
- Blood work: chemistry (particularly BUN, Cr), LFT, and CBC, regardless of treatment strategy
Diagnostic Procedures/Other
Indirect and/or direct laryngoscopy and fine needle aspiration biopsy to determine stage of disease, as well as histologic confirmation (3)[C] é á
Test Interpretation
- Laryngoscopy: fungating, friable tumor with heaped-up edges and granular appearance, with multiple areas of central necrosis and exudate surrounding areas of hyperemia
- Squamous cell carcinoma in 95% of cases (3)[C]
TREATMENT
- Early laryngeal cancer (e.g., stage I or II) is often treated with single-modality therapy (16)[A]. No difference in overall survival between radiation therapy (RT), open surgery, and endoscopic surgery (6)[A]
- Increased use of endolaryngeal surgery (transoral endoscopic) with or without laser with similar survival rates as RT and open surgery.
- Advantage of endolaryngeal surgery is voice and laryngeal function preservation compared to open and shorter treatment course compared to RT. Voice preservation outcomes similar between endolaryngeal surgery and RT (6)[A]
- RT and/or surgery, including laser excision surgery, is designed with preserving vocal function (16)[A].
- Advanced laryngeal cancer is increasingly treated with chemoradiation therapy (combination of chemotherapy and RT).
- Disadvantages of RT include prolonged course of treatment and treatment of recurrence is limited to open surgery.
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. Swishing with viscous lidocaine can be helpful as well. é á
ISSUES FOR REFERRAL
- ENT for direct visualization of larynx; biopsy and surgery
- Depending on patient 's management plan, nutritional and dental consultations are needed.
- Treatment may result in need for voice rehabilitation and be the cause of social isolation, job loss, and depression; therefore, refer to speech therapist, psychologist, social work, and/or support groups as indicated.
ADDITIONAL THERAPIES
Radiotherapy é á
- There is increased focus on RT, combined chemotherapy and RT, and function-preserving laryngectomy surgery due to patient fear of voice loss (17)[A].
- Early disease may be treatable by either RT or laser cordectomy on an outpatient basis. No randomized controlled trial has proven superiority of either when last reviewed by Cochrane in 2014.
SURGERY/OTHER PROCEDURES
- 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 RT 4 to 5 weeks after surgery depending on the stage of disease (2)[A].
INPATIENT CONSIDERATIONS
Admission Criteria/Initial Stabilization
- More advanced disease, surgical intervention, and complication management
- Nutritional or airway issues/complications
- Primarily outpatient care
ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
Patient may remain fully active unless debilitated from more advanced disease and/or greater degree of surgery. é á
Patient Monitoring
- Complete otolaryngologic exam for at least the first 2 years after primary treatment (3)[A]
- Repeat indirect laryngoscopy and complete head and neck exams periodically for at least 5 years after treatment to detect early recurrence or second primary. Second primary tumors reported in 25% of patients (16)[A]
- Yearly chest x-rays and LFT monitoring for metastatic disease
- Posttreatment surveillance for recurrence with PET/CT can be better than traditional CT and/or MRI alone due to anatomic changes from treatment (3)[C].
- 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.
- 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 EDUCATION
- Material is available from local Cancer Society branch.
- Secondary prevention to address all risk factors especially smoking cessation
PROGNOSIS
- Early disease is expected to have 75 " ô95% cure rate (depending on site, size, and depth of tumor invasion) (1,16)[A].
- Most recurrences occur within 2 years of initial treatment (3)[C].
- 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 (2)[A].
COMPLICATIONS
- Temporary odynophagia or dysphagia secondary to mucositis and/or thrush during RT
- Radiation skin burns, xerostomia with RT
- 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 RT (18)[C]
REFERENCES
11 Howlader é áN, Noone é áAM, Krapcho é áM, et al, eds. SEER Cancer Statistics Review, 1975 " ô2012. Bethesda, MD: National Cancer Institute; 2015. http://seer.cancer.gov/csr/1975_2012/. Accessed June 12, 2015.22 American Cancer Society. Cancer Facts and Figures, 2015. Atlanta, GA: American Cancer Society; 2015. http://www.cancer.org/research/cancerfactsstatistics/cancerfactsfigures2015/. Accessed June 12, 2015.33 Chu é áEA, Kim é áYJ. Laryngeal cancer: diagnosis and preoperative work-up. Otolaryngol Clin North Am. 2008;41(4):673 " ô695.44 La Vecchia é áC, Zhang é áZF, Altieri é áA. Alcohol and laryngeal cancer: an update. Eur J Cancer Prev. 2008;17(2):116 " ô124.55 Brennan é áJA, Boyle é áJO, Koch é áWM, et al. Association between cigarette smoking and mutation of the p53 gene in squamous-cell carcinoma of the head and neck. N Engl J Med. 1995;332(11):712 " ô717.66 Warner é áL, Chudasama é áJ, Kelly é áCG, et al. Radiotherapy versus open surgery versus endolaryngeal surgery (with or without laser) for early laryngeal squamous cell cancer. Cochrane Database Syst Rev. 2014;(12):CD002027.77 Bhattacharyya é áS, Mandal é áS, Banerjee é áS, et al. Cannabis smoke can be a major risk factor for early-age laryngeal cancer " öa molecular signaling-based approach. Tumour Biol. 2015;36(8):6029 " ô6036.88 Islami é áF, Tramacere é áI, Rota é áM, et al. Alcohol drinking and laryngeal cancer: overall and dose-risk relation " öa systematic review and meta-analysis. Oral Oncol. 2010;46(11): 802 " ô810.99 Sereg-Bahar é áM, Jerin é áA, Hocevar-Boltezar é áI. Higher levels of total pepsin and bile acids in the saliva as a possible risk factor for early laryngeal cancer. Radiol Oncol. 2015;49(1):59 " ô64.1010 Wagner é áM, Bolm-Audorff é áU, Hegewald é áJ, et al. Occupational polycyclic aromatic hydrocarbon exposure and risk of larynx cancer: a systematic review and meta-analysis. Occup Environ Med. 2015;72(3):226 " ô233.1111 Centers for Disease Control and Prevention. Human papillomavirus-associated cancers " öUnited States, 2004 " ô2008. MMWR Morb Mortal Wkly Rep. 2012;61:258 " ô261.1212 Bisht é áM, Bist é áSS. Human papilloma virus: a new risk factor in a subset of head and neck cancers. J Cancer Res Ther. 2011;7(3):251 " ô255.1313 Kreimer é áAR, Clifford é áGM, Boyle é áP, et al. Human papillomavirus types in head and neck squamous cell carcinomas worldwide: a systematic review. Cancer Epidemiol Biomarkers Prev. 2005;14(2):467 " ô475.1414 Leoncini é áE, Nedovic é áD, Panic é áN, 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 " ô1011.1515 Hong é áWK, Lippman é áSM, Itri é áLM, et al. Prevention of second primary tumors with isotretinoin in squamous-cell carcinoma of the head and neck. N Engl J Med. 1990;323(12):795 " ô801.1616 National Cancer Institute. Laryngeal Cancer Treatment " öfor health professionals (PDQ é «). http://www.cancer.gov/cancertopics/pdq/treatment/laryngeal/HealthProfessional/page1. Accessed June 10, 2015.1717 Sherman é áEJ, Fisher é áSG, Kraus é áDH, et al. TALK score: development and validation of a prognostic model for predicting larynx preservation outcome. Laryngoscope. 2012;122(5):1043 " ô1050.1818 Alkan é áS, Baylancicek é áS, Cift â žic é áM, et al. Thyroid dysfunction after combined therapy for laryngeal cancer: a prospective study. Otolaryngol Head Neck Surg. 2008;139(6):787 " ô791.
ADDITIONAL READING
- D 'Cruz é áAK, Sharma é áS, Pai é áPS. Current status of near-total laryngectomy: review. J Laryngol Otol. 2012;126(6):556 " ô562.
- Huang é áSH, Lockwood é áG, Irish é áJ, et al. Truths and myths about radiotherapy for verrucous carcinoma of larynx. Int J Radiat Oncol Biol Phys. 2009;73(4):1110 " ô1115.
- Hutcheson é áKA, Lewin é áJS. Functional outcomes after chemoradiotherapy of laryngeal and pharyngeal cancers. Curr Oncol Rep. 2012;14(2):158 " ô165.
- Misono é áS, Marmor é áS, Yueh é áB, et al. T1 glottic carcinoma: do comorbidities, facility characteristics, and sociodemographics explain survival differences across treatment? Otolaryngol Head Neck Surg. 2015;152(5):856 " ô862.
- Pfister é áDG, Laurie é áSA, Weinstein é áGS, 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 " ô3704.
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
- Malignant tumor of larynx (disorder)
- Primary malignant neoplasm of larynx
- Primary malignant neoplasm of laryngeal cartilage
- Primary malignant neoplasm of glottis
- Primary malignant neoplasm of supraglottis
- Primary malignant neoplasm of subglottis
CLINICAL 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.