Basics
Description
Diverse group of malignancies; many histologic types. The vast majority (~90%) of head and neck cancers are squamous cell carcinomas (HNSCC). This review will focus on HNSCC.
- Characterized by region: pharynx, larynx, oral cavity, salivary glands, nasal cavity, and sinuses
Epidemiology
- More common in males than females. Incidence increases with age, median age = 60s.
- Strongly associated with tobacco, alcohol, and viral infections (oncogenic human papillomavirus [HPV] and Epstein-Barr virus [EBV])
- HPV-positive cancers occur in younger patients, ages 40-50 years, with male predominance.
Incidence
Worldwide, ~600,000 new cases yearly; 50,000 new cases in the United States. Sixth most common cancer (CA) worldwide.
- Overall incidence is stable; however, incidence of HPV-positive tumors is increasing and HPV-negative tumor incidence is decreasing.
Prevalence
Currently, 275,000 people in the United States have oropharyngeal CA.
- Prevalence of HPV in HNSCC is ~20%, with oropharyngeal sites being ~40% HPV positive.
Etiology and Pathophysiology
- Tobacco, alcohol, and HPV and EBV are known causative agents. EBV is associated with nasopharyngeal CA, whereas HPV is associated with oropharyngeal CA.
- HPV-positive and HPV-negative tumors are distinct entities.
- HPV-positive tumors have less mutations compared to those that are HPV negative.
- HPV-positive tumors may exhibit inactivation of p53 and Rb tumor suppressor proteins by viral oncoproteins E6 and E7, respectively.
- TP53 mutation is common in HPV-negative tumors and is an early event in disease progression.
Genetics
Positive family history confers twice the risk of HNSCC. This may be due to polymorphisms in genes encoding enzymes involved in the metabolism of tobacco and alcohol.
Risk Factors
Distinct risk factors exist for HPV-positive and HPV-negative HNSCC.
- Dose-dependent relationship between smoking and HNSCC. Alcohol is an additional risk factor.
- HPV-positive HNSCC is linked to oral sex, high number of lifetime sexual partners (oral and genital), and other sexual risk factors.
- Other possible risk factors include occupational exposures (nickel, woodworking, textiles), poor dental hygiene, use of mouthwash, betel quid, preserved/salted foods in childhood, and low-fiber diet.
General Prevention
- Avoidance of tobacco and alcohol
- Minimization of sexual risk factors
- HPV vaccination may prevent some HPV HNSCC. Investigations are underway.
Commonly Associated Conditions
- Other primary malignancies are common, especially among smokers.
- Medical comorbidities that occur with chronic alcohol and tobacco abuse may be present.
- Malnutrition frequently co-occurs.
Diagnosis
History
Historical features vary based on site of tumor. Complete history is necessary. Symptoms are nonspecific, making diagnosis difficult.
- Symptoms may include sore throat, ear pain, dysphagia, chronic cough, stridor, voice changes, hoarseness, odynophagia, oral ulcer, and neck mass.
- May present with symptoms of metastatic disease: pain, liver dysfunction, etc.
Physical Exam
Complete physical, including head and neck exam. Attention to palpable masses, lymph nodes, and oropharyngeal lesions such as leukoplakia, erythroplakia, or ulcerations.
- Palpation of neck region, tongue, floor of mouth, examination of ears and nose, and cranial nerve examination
- General assessment of functional status
- If concerning findings are noted, prompt referral to specialist is warranted.
Differential Diagnosis
- Upper respiratory tract infection
- Vocal cord dysfunction
- Lymphoma
- Branchial cleft cyst
- Metastatic disease
Diagnostic Tests & Interpretation
Initial Tests (lab, imaging)
- Lab investigations include CBC, CMP, and thyroid function tests to assess for underlying comorbid illnesses prior to therapy (1)[C].
- Direct visualization via endoscopy is needed for diagnosis and to determine extent (1)[C].
- CT/MRI of head and neck including skull base to determine extent of disease and assess for lymphadenopathy (1)[C].
- Imaging of chest may be warranted.
Follow-up tests & special considerations
- For oropharyngeal sites, HPV testing (immunohistochemistry [IHC] for p16 expression or HPV in situ hybridization [ISH]) is mandatory.
- Nutritional status and swallowing capabilities warrant careful consideration. Select patients may benefit from percutaneous endoscopic gastrostomy (PEG) tube placement.
Diagnostic Procedures/Other
- Biopsy of mass and/or involved lymph nodes is crucial to diagnosis.
- Positron emission tomography-computed tomography (PET-CT) can be used in certain cases to evaluate for distant metastases.
Test Interpretation
Treatment plan is contingent on biopsy results and TNM staging.
- HPV status provides prognostic information, but treatment of HPV-positive and HPV-negative HNSCC is identical.
Treatment
General Measures
- Education on cessation of smoking/alcohol
- Treatment approach depends on functional status, goals of therapy, TNM staging, and others.
- Single-modality treatment (surgery or radiation) is often used in early stage disease (American Joint Committee on Cancer [AJCC] stage I/II). Combination approach is necessary for locally advanced disease.
- Treatment of metastatic disease may involve both palliative radiation and chemotherapy.
Medication
First Line
- Cisplatin-based chemotherapy with radiation improves locoregional control in laryngeal CA (2)[A].
- Cetuximab + concurrent radiation increases survival compared to radiation alone in locoregionally advanced disease (3)[A].
- When induction therapy is used, cisplatin + fluorouracil + docetaxel has a survival benefit compared to cisplatin + fluorouracil (4)[A]. It is unclear whether induction therapy has a survival benefit compared to concurrent chemoradiation.
- Cetuximab + chemotherapy increases survival in the metastatic setting.
Second Line
Cetuximab can be used as a single agent for recurrent or metastatic HNSCC in those who had prior platinum chemotherapy.
Issues for Referral
- A multidisciplinary team, including medical and radiation oncology and surgery, is ideal.
- Ancillary services such as speech/swallow therapy, nutrition, palliative care, and psychology are helpful.
Additional Therapies
Radiation is a mainstay of treatment. Intensity-modulated radiation therapy (IMRT) minimizes adverse effects without compromising survival (5)[A]. This has become standard of care.
- Radiation dose is dependent on clinical characteristics including use of concurrent chemotherapy.
- Conventional fractionation dose generally total of 66-72 Gy.
- Postoperative radiation may be necessary depending on tumor characteristics. Postoperative radiation should commence within 6 weeks or less after surgery.
Surgery/Other Procedures
- Surgery can be curative in early-stage disease. Surgical oncology should be involved early in the multidisciplinary team approach.
- Selective neck dissection may be performed if high suspicion of occult positive lymph nodes (N0). Radical (or modified radical) neck dissections are standard of care for lymph node positive for disease (6)[C].
Complementary & Alternative Therapies
Half of the U.S. population with cancer use some form of complementary/alternative medicine (CAM) (7).
- The patient and his or her providers should discuss use of CAM to ensure no adverse effects/interactions will occur.
Inpatient Considerations
Admission Criteria/Initial Stabilization
- HNSCC is generally managed in the outpatient setting. Admission for surgery and complications may necessitate inpatient status.
- For example: Airway compromise, bleeding or infectious complications, and severe malnutrition may need inpatient treatment.
IV Fluids
NS can be used for fluid resuscitation if oral hydration is difficult. Such patients may need alternate enteric access.
Nursing
Nursing care considerations include wound care, monitoring of fluid/nutrition intake, monitoring for signs and symptoms of aspiration and difficulty swallowing, and pain control.
Discharge Criteria
Discharge considerations include resolution of issue that required admission, good PO intake or tolerating tube feeds, etc.
Ongoing Care
Follow-up Recommendations
NCCN guidelines recommend follow-up every 1-3 months for 1 year, every 2-6 months in the second year, every 4-8 months in years 3-5, and yearly thereafter.
- Thyroid-stimulating hormone (TSH) and dental exams at regular intervals
- Chest imaging as necessary based on risk factors
Patient Monitoring
- Disease recurrence is a frequent cause of death. Distant metastases may be discovered at any point in those who initially present with locally advanced disease.
- Monitoring for secondary malignancies is necessary; risk factors for HNSCC are shared between other cancers.
Diet
Dietary modifications may be necessary if swallow difficulty is present.
Patient Education
- Discussions including disease process, anticipated treatments and procedures, risks, side effects, prognosis, and end-of-life wishes are necessary.
- Patient should monitor for malnutrition, decreasing oral intake, aspiration, weight loss, difficulty swallowing, or signs of infection that may prompt urgent or emergent care.
Prognosis
Prognosis is based on TNM staging and HPV status, including the following:
- Vascular or lymphatic invasion, positive surgical margins, extracapsular spread, perineural involvement, pT3 or pT4 primary nodal involvement in level IV or level V, N2 or N3 nodal disease, and metastasis
- HPV positivity improves prognosis in oropharyngeal cancers. HPV-positive tumors show better response to induction therapy and concurrent chemoradiation.
- Overall 5-year survival is 60%. Stage I disease has a 90% 5-year survival. Median survival for metastatic disease is <1 year.
Complications
- Complications are dependent on tumor site and therapeutic modality. May include pain, infection, xerostomia, dysphagia, speech difficulties, and cosmetic deformities.
- Platinum-based chemotherapies can result in nephrotoxicity, neuropathy, hearing loss, and bone marrow suppression.
References
1.Hamoir M, Vander Poorten V, Chantrain G, et al. Initial work-up in head and neck squamous cell carcinoma. B-ENT. 2005;Suppl 1:129-132.
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2.Forastiere AA, Zhang Q, Weber RS, et al. Long-term results of RTOG 91-11: a comparison of three nonsurgical treatment strategies to preserve the larynx in patients with locally advanced larynx cancer. J Clin Oncol. 2013;31(7):845-852.
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3.Bonner JA, Harari PM, Giralt J, et al. Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med. 2006;354(6):567-578.
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4.Posner MR, Hershock DM, Blajman CR, et al. Cisplatin and fluorouracil alone or with docetaxel in head and neck cancer. N Engl J Med. 2007;357(17):1705-1715.
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5.Marta GN, Silva V, de Andrade Carvalho H, et al. Intensity-modulated radiation therapy for head and neck cancer: systematic review and meta-analysis. Radiother Oncol. 2014;110(1):9-15. doi: 10.1016/j.radonc.2013.11.010.
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6.Ferlito A, Rinaldo A, Silver CE, et al. Elective and therapeutic selective neck dissection. Oral Oncol. 2004;42(1):14-25.
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7.Richardson MA, Sanders T, Palmer JL, et al. Complementary/alternative medicine use in a comprehensive cancer center and the implications for oncology. J Clin Oncol. 2000;18(13):2505-2514.
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Additional Reading
- Baxi S, Fury M, Ganly I, et al. Ten years of progress in head and neck cancers. J Natl Compr Canc Netw. 2012;10(7):806-810.
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- Benson E, Li R, Eisele D, et al. The clinical impact of HPV tumor status upon head and neck squamous cell carcinomas. Oral Oncol. 2014;50(6):565-574.
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- Haddad RI, Shin DM. Recent advances in head and neck cancer. N Engl J Med. 2008;359(11):1143-1154.
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- Mehanna, H, Paleri, V, West, CM. et al. Head and neck cancer-Part 1: epidemiology, presentation, and prevention. BMJ. 2010;341:663-666.
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- National Comprehensive Cancer Network. NCCN guidelines version 2.2013 head and neck cancers. http://www.nccn.org.
Codes
ICD09
- 149.0 Malignant neoplasm of pharynx, unspecified
- 161.9 Malignant neoplasm of larynx, unspecified
- 142.9 Malignant neoplasm of salivary gland, unspecified
- 147.9 Malignant neoplasm of nasopharynx, unspecified site
- 148.9 Malignant neoplasm of hypopharynx, unspecified site
- 160.9 Malignant neoplasm of accessory sinus, unspecified
ICD10
- C14.0 Malignant neoplasm of pharynx, unspecified
- C32.9 Malignant neoplasm of larynx, unspecified
- C08.9 Malignant neoplasm of major salivary gland, unspecified
- C11.9 Malignant neoplasm of nasopharynx, unspecified
- C13.9 Malignant neoplasm of hypopharynx, unspecified
- C31.9 Malignant neoplasm of accessory sinus, unspecified
SNOMED
- 363507003 Malignant tumor of pharynx (disorder)
- 363429002 Malignant tumor of larynx (disorder)
- 255072001 Malignant tumor of salivary gland (disorder)
- 187692001 Malignant tumor of nasopharynx (disorder)
- 363399006 Malignant tumor of hypopharynx (disorder)
Clinical Pearls
- High index of suspicion must be maintained as symptoms are nonspecific, and changing epidemiology further confounds diagnosis.
- A multidisciplinary approach to treatment is crucial.
- The clinician must monitor closely for recurrence, second primary malignancies, and long-term effects of treatment.