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head & neck cancer (HNC)

Classification: (see TMN classification of head & neck cancer) Etiology: risk factors: 1) tobacco: 90% of patients are smokers 2) alcohol: 75% of patients abuse alcohol 3) combined use of alcohol & tobacco synergistically increases risk [1] 4) Epstein-Barr virus* 5) papillomavirus (HPV-16) [1,16] - risk factor for oropharyngeal cancer in subset of non-smokers; [1] - oropharyngeal squamous cell carcinoma* in person who has never smoked is mostly likely assoviated with HPV 6) diabetes mellitus [8] 7) GERD [19] * greater abundance oral Corynebacterium & Kingella associated with reduced risk [20] * 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 [1] - public recognition of risks & sign/symptoms poor [7] Pathology: 1) 2% of all cancers 2) 95% are squamous cell carcinomas 3) may arise from foci of leukoplakia 4) 20% risk of 2nd cancer within 2 years a) esophageal cancer b) lung cancer 5) HPV & EBV-associated head & neck cancers occur almost exclusively within the oropharynx & are associated with better prognosis [1] 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 [1] - 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 [1] Laboratory: - papillomavirus 16 Ag in tissue [1,16] - breath analysis using mass spectroscopy for non-invasive diagnosis of early-stage head & neck squamous cell carcinoma [27] - serum TSH with reflex to free T4 in serum (after radiation therapy) [29] - see ARUP consult [2] Special laboratory: 1) pan-upper-endoscopy a) laryngoscopy* b) nasopharyngoscopy c) bronchoscopy d) esophagoscopy 2) biopsy a) fine-needle aspiration (FNA) b) nasopharynx c) base of tongue d) piriform sinus e) tonsil f) enlarged lymph node 1] avoid excisional biopsy of lymph nodes in the neck because it may discrupt tissue planes compromising surgical resection 2] use fine-needle aspiration (FNA) 3] 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 [1] - however, screening for lung cancer with low-dose CT of the lung if indicated by smoking history Complications: - 2nd cancer within 2 years (see pathology) - distant metastatic cancer in 10% of patients [1] - complications of treatment - damage to cranial nerves & sensory nerves - xersostomia - dysphagia - dysphonia - dysgeusia - fibrosis - dental problems - esophageal stricture [1] - complications in survivors [17] - 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) [17,29] 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 Staging: - 30-40% of patients present with stage I or II disease [25] - see TMN classification of head & neck cancer Management: 1) stages 1 or 2 (no lymph node involvement) [1] - surgery or radiation therapy with intent to cure - radiation therapy preferred for laryngeal carcinoma [1] - 70-90% of patients with long-term survival [25] 2) stages 3 & 4 without distant metastases - surgery with adjuvant chemotherapy & radiation therapy - chemoradiation with cisplatin/5-FU [22] - radiation therapy + cetuximab improves survival [2,11] - carboplatin-based chemoradiation associated with 15% improvement in overall survival vs cetuximab [28] 3) metastatic disease or recurrence - chemotherapy is palliative, but does not prolong survival 4) surgical resection a) resectable disease b) neck dissection c) exceptions 1] nasopharyngeal carcinoma (tumors are radiosensitive) 2] laryngeal cancer a] voice preservation b] survival similar 5) 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 [1] - cisplatin given concurrently with radiotherapy - radiation therapy followed by chemotherapy has no role [1] 6) radiation therapy for local mass effects - intensity-modulated RT (IMRT) [22] - prophylactic gabapentin may reduce opioid use post radiation [26] - radiotherapy plus cisplatin or cetuximab [11] - proton beam therapy with less toxicity & better swallowing & quality-of-life outcomes vs conventional radiotherapy [26]. 7) chemotherapy a) 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 [1] b) combination chemotherapy - cisplatin/docetaxel/fluorouracil induction therapy [18] - cisplatin/cetuximab/fluorouracil + pembrolizumab for patients with advanced disease not amenable to surgery or radiation therapy [1] - pembrolizumab alone if PDL-1 positive c) may effect favorable response d) does not improve overall survival with metastatic disease e) pembrolizumab (Keytruda) for metastatic or recurrent HNSCC with disease progression on or after platinum-containing chemotherapy f) durvalumab, tremelimumab or combination for metastatic head & neck cancer [21] - median overall survival 7.6 months for combination [21] 8) marijuana use is associated with better quality-of-life in patients with newly diagnosed head & neck cancers [23] 9) prognosis: a) 5 year survival for stage 1 disease > 80% b) most patients diagnosed with stage 3-4 disease; 5 year survival < 40-50% c) HPV* & EBV-associated head & neck cancers are associated with better prognosis [1] d) small localized disease, longer time to recurrence, site of recurrence in larynx or nasopharynx associated with better prognosis [1] 10) small, localized recurrent head & neck cancer following a long disease-free interval, may be cured with surgery & adjuvant radiation 11) follow-up - every 1-3 months for 1st year, decreasing frequency through year 5, then annually [1] - tobacco cessation & abstinence from alcohol counseling - direct physical examination +/- laryngoscopy [1] - thyroid function testing after radiation therapy (median 1.5 years) [29] - routine imaging not indicated [1] * therapy not affected [1]

Interactions

disease interactions

Related

TMN classification of head & neck cancer

Specific

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)

General

malignant neoplasm (cancer) head & neck neoplasm

Database Correlations

OMIM 275355

References

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  2. ARUP Consult: Head and Neck Cancer The Physician's Guide to Laboratory Test Selection & Interpretation https://www.arupconsult.com/content/head-and-neck-cancer
  3. American Society of Clinical Oncology: Clinical Practice Guideline for the Use of Larynx-Preservation Strategies in the Treatment of Laryngeal Cancer http://www.asco.org/portal/site/ASCO/menuitem.5d1b4bae73a9104ce277e89a320041a0/?vgnextoid=7f1bac487ddcb010VgnVCM100000ed730ad1RCRD
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  21. Fuerst ML with comments by Klil-Drori AJ Durvalumab Combo Slows PD-L1-neg Advanced Head and Neck Cancer. Increase in 'clinically relevant' overall survival, with manageable toxicity. MedPage Today. ASCO Reading Room 05.03.2018 https://www.medpagetoday.com/reading-room/asco/immunotherapy/72666 - Siu L, et al A randomized, open-label, multicenter, global phase 2 study of durvalumab (D), tremelimumab (T), or D plus T in patients with PD-L1 low/negative recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC): CONDOR Int J Rad Oncol Biol Physics 2018; 100 (5): 1307. Not indexed in PubMed
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  28. Sun L, Candelieri-Surette D, Anglin-Foote T et al Cetuximab-Based vs Carboplatin-Based Chemoradiotherapy for Patients With Head and Neck Cancer. JAMA Otolaryngol Head Neck Surg. 2022;148(11):1022-1028. PMID: 36136306 PMCID: PMC9501776 (available on 2023-09-22) https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2796301
  29. Boomsma MJ, Bijl HP, Langendijk JA. Radiation-induced hypothyroidism in head and neck cancer patients: a systematic review. Radiother Oncol. 2011 Apr;99(1):1-5. PMID: 21459468 Review.
  30. National Cancer Institute Head and Neck Cancer - Health Professional version https://www.cancer.gov/types/head-and-neck/hp