head & neck cancer (HNC)

Classification

(see TMN classification of head & neck cancer)

Etiology

risk factors:

• tobacco: 90% of patients are smokers
• alcohol: 75% of patients abuse alcohol
• combined use of alcohol & tobacco synergistically increases risk
• Epstein-Barr virus*
• papillomavirus (HPV-16)
  • risk factor for oropharyngeal cancer in subset of non-smokers;
  • oropharyngeal squamous cell carcinoma* in person who has never smoked is mostly likely assoviated with HPV
• diabetes mellitus
• GERD

* greater abundance oral Corynebacterium & Kingella associated with reduced risk

* positive cervical lymph node plus slightly enlarged tonsil on the same side constitutes oropharyngeal carcinoma [NEJM knowledge+]

Epidemiology

• HPV & EBV-associated head & neck cancers occur in younger patients
• public recognition of risks & sign/symptoms poor

Pathology

• 2% of all cancers
• 95% are squamous cell carcinomas
• may arise from foci of leukoplakia
• 20% risk of 2nd cancer within 2 years
  • esophageal cancer
  • lung cancer
• HPV & EBV-associated head & neck cancers occur almost exclusively within the oropharynx & are associated with better prognosis

Genetics

• associated with defects in ING1
• implicated genes: SAGE1, HES2, ARHGAP23, BAGE1, MTUS1, BCL9L, ASXL3, ING3, TP53, TP63, PTEN, TNFRSF10B, PRB2, PRB4

Clinical manifestations

• an isolated neck mass is a common presentation
  • enlarged upper cervical lymph node
  • firm, fixed, not associated with antecedent infection
• localized mouth, tooth throat or ear pain
• hoarseness
• hemoptysis
• painless, non-healing mucosal ulcer
• dysphagia or odynophagia
• proptosis
• diplopia or loss of vision
• hearing loss
• persistent unilateral sinusitis
• unilateral tonsillar enlargement in adults

Laboratory

• papillomavirus 16 Ag in tissue
• breath analysis using mass spectroscopy for non-invasive diagnosis of early-stage head & neck squamous cell carcinoma
• serum TSH with reflex to free T4 in serum (after radiation therapy)
• see ARUP consult

Diagnostic procedures

• pan-upper-endoscopy
  • laryngoscopy*
  • nasopharyngoscopy
  • bronchoscopy
  • esophagoscopy
• biopsy
  • fine-needle aspiration (FNA)
  • nasopharynx
  • base of tongue
  • piriform sinus
  • tonsil
  • enlarged lymph node
    • avoid excisional biopsy of lymph nodes in the neck because it may discrupt tissue planes compromising surgical resection
    • use fine-needle aspiration (FNA)
    • if FNA is negative, a head & neck surgeon should perform excisional lymph node biopsy, anticipating potential resection

* if diagnosis based on biopsy of cervical lymph node, the next step is determining the primary site; pan-upper-endoscopy indicated including direct laryngoscopy under anesthesia with tonsillectomy EVEN if flexible laryngoscopy is unremarkable

Radiology

• chest X-ray
• computed tomography vs MRI to evaluate primary tumor & lymph node involvement
• PET scan to detect distant metastases
• routine imaging after negative post-treatment scan not indicated
  • imaging determined by signs/symptoms suggesting recurrence
  • however, screening for lung cancer with low-dose CT of the lung if indicated by smoking history

Staging

• 30-40% of patients present with stage I or II disease
• see TMN classification of head & neck cancer

Complications

• 2nd cancer within 2 years (see pathology)
• distant metastatic cancer in 10% of patients
• complications of treatment
  • damage to cranial nerves & sensory nerves
  • xersostomia
  • dysphagia
  • dysphonia
  • dysgeusia
  • fibrosis
  • dental problems
  • esophageal stricture
• complications in survivors
  • cervical dystonia
  • fatigue
  • lymphedema
  • shoulder dysfunction
  • gastroesophageal reflux disease
  • trismus
  • dysphagia
  • osteonecrosis
  • dysgeusia (altered sense of taste)
  • hearing loss
  • hypothyroidism after radiation therapy (median 1.5 years)

• disease interaction(s) of diabetes mellitus with head & neck cancer

Differential diagnosis

• leukoplakia
• lichen planus
• oropharyngeal Candidiasis
• lung cancer
  • presentation with mid to upper cervical lymph node involvement increases likelihood of head & neck primary tumor; lower cervical to supraclavicular nodes increase likelihood of primary lung tumor

Management

• stages 1 or 2 (no lymph node involvement)
  • surgery or radiation therapy with intent to cure
  • radiation therapy preferred for laryngeal carcinoma
  • 70-90% of patients with long-term survival
• stages 3 & 4 without distant metastases
  • surgery with adjuvant chemotherapy & radiation therapy
  • chemoradiation with cisplatin/5-FU
  • radiation therapy + cetuximab improves survival
  • carboplatin-based chemoradiation associated with 15% improvement in overall survival vs cetuximab
• metastatic disease or recurrence
  • chemotherapy is palliative, but does not prolong survival
• surgical resection
  • resectable disease
  • neck dissection
  • exceptions
    • nasopharyngeal carcinoma (tumors are radiosensitive)
    • laryngeal cancer
      • voice preservation
      • survival similar
• combined adjuvant chemotherapy & radiation therapy improves survival in patients with resected squamous cell carcinoma associated with positive margins or lymph node metastases with extracapsular extension
  • cisplatin given concurrently with radiotherapy
  • radiation therapy followed by chemotherapy has no role
• radiation therapy for local mass effects
  • intensity-modulated RT (IMRT)
  • prophylactic gabapentin may reduce opioid use post radiation
  • radiotherapy plus cisplatin or cetuximab
  • proton beam therapy with less toxicity & better swallowing & quality-of-life outcomes vs conventional radiotherapy.
• chemotherapy
  • cisplatin alone or as part of chemoradiation
    • 100 mg per square meter of body-surface area every 21 days for 3 cycles
    • cetuximab preferred vs cisplatin if renal insufficiency
  • combination chemotherapy
    • cisplatin/docetaxel/fluorouracil induction therapy
    • cisplatin/cetuximab/fluorouracil + pembrolizumab for patients with advanced disease not amenable to surgery or radiation therapy
    • pembrolizumab alone if PDL-1 positive
  • may effect favorable response
  • does not improve overall survival with metastatic disease
  • pembrolizumab (Keytruda) for metastatic or recurrent HNSCC with disease progression on or after platinum-containing chemotherapy
  • durvalumab, tremelimumab or combination for metastatic head & neck cancer
    • median overall survival 7.6 months for combination
• marijuana use is associated with better quality-of-life in patients with newly diagnosed head & neck cancers
• prognosis:
  • 5 year survival for stage 1 disease > 80%
  • most patients diagnosed with stage 3-4 disease; 5 year survival < 40-50%
  • HPV* & EBV-associated head & neck cancers are associated with better prognosis
  • small localized disease, longer time to recurrence, site of recurrence in larynx or nasopharynx associated with better prognosis
• small, localized recurrent head & neck cancer following a long disease-free interval, may be cured with surgery & adjuvant radiation
• follow-up
  • every 1-3 months for 1st year, decreasing frequency through year 5, then annually
  • tobacco cessation & abstinence from alcohol counseling
  • direct physical examination +/- laryngoscopy
  • thyroid function testing after radiation therapy (median 1.5 years)
  • routine imaging not indicated

* therapy not affected

More general terms

• malignant neoplasm (cancer)
• head & neck neoplasm

More specific terms

• head & neck squamous cell carcinoma
• laryngeal carcinoma
• malignant neoplasm of ethmoid sinus
• malignant neoplasm of maxillary sinus
• nasopharyngeal carcinoma (NPC)
• oral cancer (oropharyngeal cancer)
• pharyngeal carcinoma (laryngopharyngeal cancer)

Additional terms

• TMN classification of head & neck cancer

Patient information

head & neck cancer patient information

Database

• OMIM: https://mirror.omim.org/entry/275355