Special Senses & Otolaryngology

Head and neck cancer: screening and presentation

Clinical Overview and When to Suspect Head and Neck Cancer

— Tobacco + alcohol (synergistic): classic for oral cavity, larynx, hypopharynx. Risk multiplies, not adds.

— HPV-16 (high-risk): drives oropharyngeal (tonsil, base of tongue) SCC in younger, often nonsmoking patients with multiple oral sex partners. Better prognosis.

— Persistent (>2–3 weeks) hoarseness, sore throat, dysphagia, odynophagia, otalgia (referred via CN IX/X), oral ulcer, or unilateral neck mass in an adult.

— Unilateral serous otitis media in an adult → suspect nasopharyngeal carcinoma obstructing Eustachian tube until proven otherwise.

— Hemoptysis, unilateral epistaxis, or cranial neuropathy in at-risk patient.

Board pearl: Any adult neck mass present >2 weeks in a smoker/drinker or HPV-risk patient is HNSCC metastasis until proven otherwise — proceed to triple endoscopy and FNA, NOT excisional biopsy.

Scope: Head and neck cancer (HNC) encompasses malignancies of the oral cavity, oropharynx, hypopharynx, larynx, nasopharynx, nasal cavity/paranasal sinuses, and salivary glands. Over 90% are squamous cell carcinomas (HNSCC).

US epidemiology: ~66,000 new cases/year; men > women (~3:1); median age 60s. Oropharyngeal SCC is rising due to HPV-16, while laryngeal and oral cavity SCC are declining with reduced smoking.

Two dominant risk profiles:

Other risks: betel/areca nut (oral cavity), EBV (nasopharyngeal carcinoma, esp. Southern Chinese/Southeast Asian), occupational wood/nickel dust (sinonasal adenocarcinoma), prior radiation, Plummer-Vinson syndrome (post-cricoid), Fanconi anemia, immunosuppression.

When to suspect on Step 3:

Screening: USPSTF gives insufficient evidence (I statement) for routine oral cancer screening in asymptomatic adults by primary care. No general population screening recommended; case-finding by annual dental visual/palpation exam is standard of care.

Presentation Patterns and Key History

— Oral cavity: non-healing ulcer, leukoplakia/erythroplakia, loose teeth, ill-fitting dentures, oral bleeding, tongue pain.

— Oropharynx (tonsil, base of tongue): sore throat, muffled "hot potato" voice, dysphagia, referred otalgia, painless cervical (level II) lymphadenopathy — often the only finding in HPV+ disease.

— Hypopharynx (pyriform sinus, post-cricoid): progressive dysphagia, weight loss, hoarseness when laryngeal invasion occurs; presents late.

— Larynx (glottic): persistent hoarseness >2 weeks is the earliest sign; supraglottic tumors cause dysphagia and referred otalgia; subglottic causes stridor/airway compromise.

— Nasopharynx: unilateral serous otitis media, epistaxis, nasal obstruction, neck mass (often bilateral level V), cranial nerve palsies (III–VI from cavernous sinus, IX–XII at skull base).

— Salivary gland: painless firm mass; pain, facial nerve weakness, or fixation suggests malignancy over pleomorphic adenoma.

— Pack-years smoking, alcohol drinks/day, smokeless tobacco, betel nut.

— Sexual history relevant to HPV exposure; HPV vaccination status.

— EBV-endemic ancestry, prior head/neck radiation, occupational exposures.

— Weight loss, dysphagia trajectory, dyspnea/stridor, dental issues.

— Prior premalignant lesions (leukoplakia, erythroplakia, lichen planus).

Key distinction: Hoarseness from glottic cancer is early and prompts urgent laryngoscopy; hoarseness from supraglottic or hypopharyngeal cancer is late, after the lesion invades the glottis — these patients present with advanced nodal disease and worse prognosis. Always image a neck mass before any "watch and wait" trial of antibiotics.

Site-specific red-flag symptoms:

Key historical items to elicit:

Constitutional/systemic clues: unintentional weight loss, anorexia, fatigue suggest advanced disease; trismus implies pterygoid muscle invasion (locally advanced).

Physical Exam Findings and Airway Assessment

— Inspect lips, buccal mucosa, hard palate, floor of mouth, anterior 2/3 tongue, gingiva, retromolar trigone.

— Erythroplakia (red velvety patch) has higher malignant potential than leukoplakia.

— Palpate tongue base and floor of mouth — submucosal tumors are often missed visually.

— Stridor (inspiratory = supraglottic/glottic; biphasic = subglottic/tracheal), accessory muscle use, drooling, tripoding — impending airway compromise.

— Pulse oximetry, capnography if available, work of breathing.

— Anticipate difficult intubation (distorted anatomy, trismus, fixed neck); have ENT and surgical airway backup.

CCS pearl: If a patient with suspected HNC presents with stridor or air hunger, order STAT ENT consult, awake fiberoptic intubation in OR, and prepare for emergent tracheostomy. Do not sedate or paralyze in the ED before securing the airway — loss of muscle tone in a distorted upper airway can be fatal.

General inspection: cachexia, voice quality (breathy, muffled, stridulous), trismus (interincisor distance <35 mm suggests pterygoid invasion), facial asymmetry, cranial nerve deficits.

Oral cavity exam (with gloved bimanual palpation):

Oropharynx: asymmetric tonsils, base-of-tongue fullness, palatal lesions. Indirect mirror or flexible fiberoptic nasopharyngolaryngoscopy is the office gold standard.

Neck exam: systematic palpation of all 6 levels (Ia/b, II, III, IV, V, VI). Document size, location, mobility, tenderness. Malignant nodes are firm, fixed, painless, often >1.5 cm; supraclavicular nodes raise concern for infraclavicular primary or distant spread.

Cranial nerve screen: CN V (facial sensation, masseter), VII (facial movement — parotid malignancy), IX/X (gag, palatal elevation), XI (shoulder shrug — level V/spinal accessory involvement), XII (tongue deviation — hypoglossal canal).

Airway/hemodynamic assessment:

Diagnostic Workup — Initial Evaluation

— Visible mucosal lesion: in-office or OR biopsy of the primary.

— Neck mass without obvious primary: fine-needle aspiration (FNA) is the procedure of choice. Never perform open excisional biopsy first — it disrupts tissue planes, worsens prognosis, and complicates definitive neck dissection.

— Ultrasound-guided FNA improves yield for cystic or deep nodes.

— p16 immunohistochemistry on oropharyngeal SCC — surrogate for high-risk HPV; positive disease has better prognosis and is staged separately (AJCC 8th edition).

— EBV-encoded RNA (EBER) in situ hybridization for nasopharyngeal carcinoma; plasma EBV DNA tracks disease burden.

— CT neck with IV contrast is the first-line cross-sectional study — defines primary extent, bone invasion, and nodal disease.

— MRI preferred for tongue base, nasopharynx, perineural spread, and skull base involvement.

— CT chest to screen for lung metastases and synchronous primary (smokers have ~5% synchronous aerodigestive malignancy).

Step 3 management: For an adult with a persistent neck mass, order: CT neck with contrast → FNA of the mass → office laryngoscopy → if FNA shows SCC and primary unidentified, proceed to PET/CT and EUA with panendoscopy + directed biopsies.

Office laryngoscopy: flexible fiberoptic nasopharyngolaryngoscopy is the first-line procedure for any persistent hoarseness, dysphagia, or unexplained neck mass in adults. Documents lesion site, size, vocal cord mobility (cord fixation = T3).

Tissue diagnosis:

HPV and EBV testing on biopsy:

Initial imaging:

Labs: CBC, CMP, albumin/prealbumin (nutrition), TSH (baseline before radiation), HIV if risk factors, hepatitis panel.

Dental and nutrition: pre-treatment dental evaluation (extract non-restorable teeth before radiation to prevent osteoradionecrosis); swallow evaluation; consider PEG tube if anticipated mucositis.

Diagnostic Workup — Advanced and Staging Studies

— Standard for stage III/IV disease, unknown primary, and post-treatment surveillance (at ~3 months after definitive therapy).

— Detects occult primary in ~25–30% of cervical SCC of unknown origin.

— Identifies distant metastases (lung, liver, bone) and synchronous tumors.

— Direct laryngoscopy, esophagoscopy, bronchoscopy ± nasopharyngoscopy.

— Maps tumor extent, identifies synchronous lesions, and obtains definitive biopsies.

— Especially for unknown primary: directed biopsies of base of tongue, tonsils (bilateral tonsillectomy), nasopharynx, pyriform sinuses.

— Suspected perineural spread (especially adenoid cystic carcinoma along CN V, VII).

— Skull base, cavernous sinus, intracranial extension.

— Tongue and tongue-base tumors (better soft-tissue contrast).

— Parotid masses (defines deep lobe and facial nerve relationship).

— HPV+ oropharyngeal SCC has its own staging with downstaged nodal categories — reflects better prognosis.

— Oral cavity staging now incorporates depth of invasion (DOI) — DOI >5 mm upstages to T2, >10 mm to T3.

— Extranodal extension (ENE) upstages nodal disease to N3b.

Board pearl: Cystic level II neck mass in an adult is HPV-related oropharyngeal SCC metastasis until proven otherwise — not a branchial cleft cyst. Order FNA with p16 testing, not "watchful waiting."

PET/CT (FDG):

Examination under anesthesia (EUA) with panendoscopy:

MRI indications (in addition to CT):

Sentinel lymph node biopsy: emerging in early oral cavity SCC (T1–T2 N0) as alternative to elective neck dissection.

Staging system (AJCC 8th edition):

Pretreatment multidisciplinary tumor board is standard of care: head/neck surgery, radiation oncology, medical oncology, pathology, radiology, dental, speech/swallow, nutrition.

Risk Stratification and Management Logic

— Surgery OR radiation with equivalent oncologic outcomes; choice based on morbidity, functional outcome, and patient/institutional expertise.

— Glottic T1: radiation or transoral laser microsurgery; both ~90% cure.

— Oral cavity T1–T2: primary surgical resection ± elective neck dissection if DOI >3–4 mm.

— Definitive chemoradiation (cisplatin + 70 Gy IMRT) for organ preservation in larynx, hypopharynx, oropharynx.

— Surgery + adjuvant RT or chemoRT for oral cavity primary, or when surgery preserves function better.

— Adjuvant chemoRT indicated for positive margins or extranodal extension (high-risk features); RT alone for intermediate-risk features (perineural invasion, lymphovascular invasion, multiple positive nodes).

— First-line: pembrolizumab (anti-PD-1) ± chemotherapy if CPS ≥1.

— Platinum-based chemo + cetuximab (EGFR inhibitor) historically.

— Reirradiation or salvage surgery for locoregional recurrence.

Step 3 management: Step 3 will rarely ask drug doses but will test the principle: HPV+ oropharyngeal cancer has superior prognosis and is currently being studied for de-escalation, but outside clinical trials, standard-dose chemoRT remains the SOC. Don't recommend de-intensified therapy off-protocol.

Treatment decisions depend on: subsite, T/N stage, HPV/EBV status, resectability, organ-preservation goals, comorbidities, performance status, and patient preference.

Early-stage (Stage I–II): single-modality therapy.

Locally advanced (Stage III–IVA/B): multimodality.

Nasopharyngeal carcinoma: chemoradiation is primary treatment (not surgery) due to anatomic location and radiosensitivity; induction chemo for bulky disease.

Metastatic/recurrent disease:

Performance status: ECOG/Karnofsky guides intensity; frail or elderly patients may receive de-escalated regimens (e.g., RT alone, weekly cisplatin instead of bolus, or cetuximab + RT).

Pharmacotherapy — Systemic Regimens

— High-dose cisplatin 100 mg/m² IV every 3 weeks × 3 cycles with 70 Gy radiation — standard for definitive and adjuvant chemoRT.

— Weekly cisplatin 40 mg/m² — better tolerated, often used in elderly or comorbid patients; non-inferior in some subgroups.

— Cetuximab + RT (Bonner regimen) — for cisplatin-ineligible patients (renal dysfunction, hearing loss, poor PS); inferior to cisplatin in HPV+ disease (RTOG 1016).

— TPF: docetaxel + cisplatin + 5-FU — used for organ preservation in larynx/hypopharynx or bulky unresectable disease before chemoRT.

— Pembrolizumab monotherapy if PD-L1 CPS ≥1 (KEYNOTE-048).

— Pembrolizumab + platinum + 5-FU regardless of CPS.

— EXTREME regimen (platinum + 5-FU + cetuximab) if immunotherapy contraindicated.

— Cisplatin: nephrotoxicity (hydrate aggressively, check Cr, eGFR ≥60 required), ototoxicity (baseline audiogram), neuropathy, severe N/V (3-drug antiemetic prophylaxis: 5HT3 + dexamethasone + NK1 antagonist), myelosuppression, electrolyte wasting (Mg²⁺, K⁺).

— Cetuximab: acneiform rash (correlates with response), hypomagnesemia, infusion reactions (premedicate; higher rates in Southeast US — alpha-gal antibody).

— Pembrolizumab: immune-related adverse events — pneumonitis, colitis, hepatitis, thyroiditis, hypophysitis. Hold drug and start steroids for grade ≥2 irAEs.

Board pearl: Before starting cisplatin, document baseline audiogram, eGFR, Mg/K, and neuropathy exam. New tinnitus or hearing loss = switch to carboplatin or cetuximab.

Concurrent chemoradiation backbones:

Induction (neoadjuvant) chemo:

Recurrent/metastatic disease (first-line):

Key toxicities and management:

Supportive care during chemoRT: opioids for mucositis pain, magic mouthwash, PEG-tube feeds, antiemetics, fluconazole if candidiasis, hydration.

Procedures and Surgical Management

— Transoral robotic surgery (TORS) — minimally invasive resection of oropharyngeal primaries; growing role in HPV+ disease.

— Transoral laser microsurgery (TLM) — early glottic and supraglottic lesions.

— Open partial laryngectomy — selected T1–T3 laryngeal cancers preserving voice.

— Total laryngectomy — T4a laryngeal/hypopharyngeal cancers, salvage after RT failure, or chondronecrosis; creates permanent tracheostoma; voice rehab via tracheoesophageal puncture (TEP) prosthesis, electrolarynx, or esophageal speech.

— Glossectomy, mandibulectomy, maxillectomy with free-flap reconstruction (radial forearm, fibula, ALT) for oral cavity primaries.

— Selective neck dissection (levels I–III or II–IV) for cN0 necks with primary tumor risk >15–20% occult nodal disease.

— Modified radical neck dissection (preserves CN XI, IJ, or SCM) for cN+ disease.

— Radical neck dissection (sacrifices all three) — rarely needed today.

— Tracheostomy for impending airway obstruction, prolonged intubation, or after large resections.

— Awake fiberoptic intubation for distorted airways.

— IMRT (intensity-modulated radiation therapy) is standard — spares parotid (reduces xerostomia), spinal cord, optic structures.

— Proton therapy for skull base, pediatric, and reirradiation cases.

— Brachytherapy for selected oral cavity recurrences.

CCS pearl: After total laryngectomy, the patient breathes only through the neck stoma — no airflow through nose/mouth. Mask ventilation will fail. Document this prominently; emergency airway = stomal intubation or replacement of laryngectomy tube.

Primary tumor surgery:

Neck dissection:

Airway management:

Radiation modalities:

Reconstruction: free tissue transfer (microvascular) is standard for large defects; restores speech, swallowing, cosmesis.

Special Populations — Elderly and Organ Impairment

— Comprehensive geriatric assessment recommended before intensive therapy; tools: G8 screen, CARG toxicity score.

— Higher risk of cisplatin toxicity (renal, ototoxicity, neuropathy); consider weekly low-dose cisplatin, carboplatin AUC 1.5 weekly, or cetuximab + RT.

— Polypharmacy review — discontinue nephrotoxins (NSAIDs, ACEi if volume-depleted) during cisplatin cycles.

— Functional outcomes (swallowing, speech) matter more — bias toward function-preserving strategies and aggressive rehab.

— Don't withhold curative therapy based on age alone — assess physiologic reserve, not chronologic age.

— eGFR <60 mL/min/1.73 m² — cisplatin generally contraindicated; substitute carboplatin (AUC 5) or cetuximab + RT.

— Aggressive IV hydration (NS pre/post cisplatin), forced diuresis, magnesium repletion mandatory.

— Avoid concurrent nephrotoxins: aminoglycosides, contrast (or pre-hydrate), NSAIDs.

— Less commonly limits HNC therapy; docetaxel and 5-FU require dose adjustment in significant dysfunction (bilirubin >1.5× ULN).

— Screen for hepatitis B reactivation before immunotherapy or rituximab-containing regimens (uncommon here but relevant).

— 5-FU can cause coronary vasospasm; pre-existing CAD warrants caution.

— Anthracyclines not used in HNC, so cardiotoxicity less relevant; cetuximab safe.

Step 3 management: Elderly patient with HNSCC and CrCl 45 mL/min → don't refuse curative chemoRT. Substitute carboplatin or cetuximab + RT and proceed with definitive treatment; outcomes are comparable with proper selection.

Elderly patients (≥70):

Renal impairment:

Hepatic impairment:

Cardiac comorbidity:

Frailty: consider RT alone with hypofractionation, palliative-intent therapy, or best supportive care if curative therapy not feasible.

Special Populations — Pregnancy, Young Adults, and HPV+ Disease

— HNC during pregnancy is rare. Diagnostic workup: prefer MRI without gadolinium; CT with abdominal shielding if needed; FNA safe.

— Treatment is individualized — surgery in any trimester possible; radiation generally deferred until postpartum; chemo avoided in 1st trimester, possible in 2nd/3rd with multidisciplinary planning.

— Termination is not mandatory; outcomes depend on stage and gestational age.

— Increasingly affects men aged 40–60, often nonsmokers, higher SES, oral HPV exposure.

— Better prognosis (5-year OS ~80%+ for HPV+ vs ~50% for HPV−).

— HPV vaccination (Gardasil-9): routine at age 11–12 (range 9–26); catch-up through age 26; shared decision-making 27–45. Vaccination prevents oncogenic HPV infection and is the cornerstone of primary prevention.

— De-escalation trials ongoing — outside trials, standard chemoRT.

— Long expected survival makes late toxicities (xerostomia, dysphagia, hypothyroidism, second cancers, osteoradionecrosis) more impactful.

— Counsel on partner transmission — established long-term partners share oral HPV exposure; no additional screening or behavioral changes recommended for partners.

— Address sexual health, identity concerns sensitively.

Board pearl: A 35-year-old man with unilateral cystic neck mass and no smoking history → think HPV+ oropharyngeal SCC, not branchial cleft cyst. FNA with p16 staining is the next step.

Pregnancy:

HPV+ oropharyngeal cancer demographics:

Pediatric head and neck malignancies: rhabdomyosarcoma (parameningeal), lymphoma, nasopharyngeal carcinoma (endemic), Langerhans cell histiocytosis — referral to pediatric oncology.

Survivorship in young HPV+ patients:

Immunocompromised (HIV, transplant): higher risk of oral SCC and HPV-related malignancies; same staging/treatment principles with attention to drug interactions and infection risk.

Complications and Adverse Outcomes

— Mucositis (RT/chemoRT): painful inflammation of oral/pharyngeal mucosa; manage with magic mouthwash, opioids, hydration, PEG-tube nutrition; avoid alcohol-based rinses.

— Dermatitis: moisturizers, silver sulfadiazine for moist desquamation.

— Xerostomia: parotid-sparing IMRT reduces incidence; pilocarpine, cevimeline, amifostine; aggressive dental fluoride.

— Dysphagia/aspiration: speech-language pathology evaluation, modified diets, swallowing exercises.

— Cisplatin toxicity: AKI, ototoxicity, neuropathy, electrolyte wasting.

— Osteoradionecrosis of mandible: spontaneous bone necrosis after RT; risk increases with dental extractions post-RT; prevent with pre-RT dental clearance; treat with pentoxifylline + tocopherol, hyperbaric O₂, or surgical debridement.

— Hypothyroidism: in 30–50% after neck RT; check TSH every 6–12 months for life.

— Carotid stenosis: accelerated atherosclerosis after RT; consider periodic carotid ultrasound, stroke prevention.

— Second primary malignancies: field cancerization — 3–5%/year risk of new aerodigestive primary, especially in continued smokers.

— Lymphedema: head and neck lymphedema after surgery + RT; manual lymphatic drainage, compression.

— Trismus: jaw stretching exercises (TheraBite).

— Tumor bleeding (carotid blowout in recurrent/post-RT disease) — emergency hemostasis, endovascular intervention.

— Stomal stenosis after laryngectomy.

Key distinction: Mucositis is acute (resolves weeks after RT); osteoradionecrosis is late (months to years). Both are managed differently — mucositis is supportive, ORN may require surgery and meticulous dental prophylaxis lifelong.

Acute treatment toxicities:

Late/chronic complications:

Airway emergencies:

Psychosocial: depression, body image disturbance, voice loss, social isolation — screen routinely.

When to Escalate Care

— Airway compromise (stridor, accessory muscle use, hypoxia) → STAT ENT + anesthesia, OR for awake fiberoptic intubation or surgical airway. Do not attempt blind nasal intubation or RSI without backup.

— Carotid blowout syndrome (sentinel bleed from neck wound or recurrent tumor) → ICU, type and cross, vascular/IR for endovascular stenting or embolization; mortality 40%+.

— Massive hemoptysis or epistaxis from advanced tumors → airway protection, IR embolization.

— Tumor lysis syndrome — rare in HNC but possible with bulky disease.

— Severe mucositis with dehydration, aspiration pneumonia, neutropenic fever during chemoRT — admit for IV fluids, antibiotics, pain control, nutritional support.

— Hypercalcemia of malignancy (PTHrP from SCC) → IV hydration, calcitonin, zoledronic acid.

— Cisplatin AKI with rising Cr, electrolyte derangements (Mg <1.0, K <3.0).

— Cranial neuropathy progression (skull base involvement).

— Otolaryngology/head-neck surgery: any suspicious lesion or neck mass >2 weeks.

— Radiation oncology and medical oncology: for treatment planning; multidisciplinary tumor board.

— Dental oncology: before RT for extractions and fluoride trays.

— Speech/swallow, nutrition, social work: at diagnosis and throughout treatment.

— Palliative care: early integration for symptom management even in curative-intent therapy.

CCS pearl: Encounter a post-laryngectomy patient with sentinel bleeding from the stoma: admit to ICU, type and cross 4–6 units, STAT IR consult for carotid angiography ± stenting, ENT at bedside. This is a pre-blowout warning.

Emergent (immediate ED/ICU):

Urgent (admit or rapid outpatient):

Specialist consultations:

Inpatient triage threshold: ≥10% weight loss, inability to maintain hydration/nutrition, uncontrolled pain, suspected aspiration.

Key Differentials — Same Category (Head and Neck Mucosal Lesions)

— Leukoplakia: white patch that cannot be wiped off; 5–17% malignant transformation; biopsy any persistent or thickened lesion.

— Erythroplakia: red velvety patch; higher malignant risk (~50%); always biopsy.

— Oral lichen planus (erosive type): chronic inflammatory; small malignant transformation risk; monitor.

— Submucous fibrosis: betel nut chewers; trismus, blanched mucosa; precancerous.

— Reactive lymphadenopathy: tender, mobile, <2 cm, recent URI; resolves in 3–4 weeks.

— Branchial cleft cyst: lateral neck (level II–III), congenital, often presents in young adults after infection. Caution: any "branchial cyst" in adults >40 is HPV+ SCC until proven otherwise.

— Thyroglossal duct cyst: midline, moves with swallowing/tongue protrusion; pediatric/young adult.

— Sialadenitis/sialolithiasis: painful, postprandial swelling of submandibular or parotid gland; sialogram or ultrasound.

— Pleomorphic adenoma (benign parotid): painless, slow-growing, mobile mass; treat with parotidectomy with facial nerve preservation; 5–10% transform to carcinoma ex pleomorphic adenoma if neglected.

— Lymphoma (Hodgkin or non-Hodgkin): rubbery, multiple nodes, B symptoms; excisional biopsy preferred (unlike SCC — flow cytometry needs intact architecture).

— Thyroid cancer: anterior neck, moves with swallowing; thyroid function, US, FNA.

— Salivary gland malignancies: mucoepidermoid carcinoma (commonest), adenoid cystic (perineural spread), acinic cell, salivary duct carcinoma.

Key distinction: Neck mass workup pathway differs by suspected etiology — SCC = FNA first; lymphoma = excisional biopsy. Don't excise a presumed SCC node — it spreads tumor and compromises curative neck dissection.

Premalignant oral lesions:

Benign head/neck masses (differential for neck mass):

Other head/neck malignancies:

Key Differentials — Other Categories

— Bacterial pharyngitis/tonsillitis (GAS) — acute, fever, exudates, tender anterior cervical nodes; rapid strep/throat culture.

— Peritonsillar abscess: trismus, "hot potato voice," uvular deviation; drainage required.

— Infectious mononucleosis (EBV): posterior cervical lymphadenopathy, splenomegaly, atypical lymphocytes, monospot+; tonsillar hypertrophy — avoid amoxicillin (rash).

— Tuberculous cervical lymphadenitis (scrofula): chronic painless lymphadenopathy, often supraclavicular; AFB stain, culture, PPR/IGRA.

— Cat-scratch disease (Bartonella): regional lymphadenopathy after cat exposure.

— HIV-related lymphadenopathy.

— Deep neck space infections: Ludwig angina, retropharyngeal abscess — airway threat, CT, drainage, IV antibiotics.

— Laryngopharyngeal reflux (LPR): chronic hoarseness, throat clearing, globus; respond to PPI + lifestyle. Still requires laryngoscopy to exclude malignancy if persistent.

— Vocal cord nodules/polyps: voice overuse; voice therapy.

— Recurrent laryngeal nerve palsy: post-thyroidectomy, mediastinal mass (lung cancer compressing left RLN), idiopathic.

— Zenker diverticulum: dysphagia, regurgitation, halitosis in elderly; barium swallow.

— Eosinophilic esophagitis: young adults, food impaction, atopy; endoscopy with biopsies.

Board pearl: Adolescent boy with unilateral nasal obstruction and recurrent epistaxis = juvenile nasopharyngeal angiofibroma. Order contrast MRI/CT and angiography first — never biopsy in clinic (catastrophic bleeding).

Infectious causes of neck mass/throat symptoms:

Voice/swallowing changes mimicking HNC:

Sinonasal masses: inverted papilloma (premalignant, unilateral), juvenile nasopharyngeal angiofibroma (adolescent males with epistaxis — biopsy contraindicated; image first).

Secondary Prevention and Long-Term Plan

— Continued smoking after HNC diagnosis reduces RT efficacy, increases recurrence, second primaries, and all-cause mortality.

— Offer varenicline or combination NRT + behavioral support (5 A's, quit lines, motivational interviewing) at every visit.

— Bupropion is alternative; avoid in seizure risk.

— Mediterranean-style, fruits/vegetables, adequate protein; avoid hot beverages (esophageal SCC risk).

— Ongoing dietitian support for chronic dysphagia; PEG-tube weaning protocols.

— Daily fluoride trays after RT, soft-bristle brushing, frequent dental cleanings (every 3–6 months).

— Avoid extractions in RT field; if needed, hyperbaric O₂ consideration.

— Document treatment summary, expected late effects, surveillance schedule.

— Share with PCP — primary care manages cardiovascular risk, screening for other cancers, vaccinations.

— Manage hypertension, diabetes, hyperlipidemia — accelerated by RT-induced atherosclerosis.

— Screen for depression, anxiety, PTSD; refer to mental health.

— Statin and antiplatelet therapy if carotid stenosis develops.

Step 3 management: At every follow-up after HNC treatment: ask about tobacco/alcohol, assess swallowing/voice/pain, check TSH yearly, examine head/neck, ensure dental follow-up, and reinforce smoking cessation — it's the single most impactful intervention you can deliver.

Tobacco cessation (highest-yield intervention):

Alcohol cessation: brief intervention, naltrexone, acamprosate, AA referral.

HPV vaccination: primary prevention; vaccinate eligible patients (9–26 routine, 27–45 shared decision-making). Does not treat existing infection but prevents future strains.

Diet and nutrition:

Dental hygiene lifelong:

Survivorship care plan (per IOM/ASCO):

Co-existing morbidity management:

Lung cancer screening: annual low-dose chest CT for eligible smokers (50–80, 20+ pack-years, currently smoking or quit <15 years) per USPSTF — particularly relevant in HNC survivors.

Follow-Up, Monitoring, and Rehabilitation

— Year 1: every 1–3 months.

— Year 2: every 2–6 months.

— Years 3–5: every 4–8 months.

— >5 years: every 12 months indefinitely (second primary risk persists).

— Complete head/neck exam with flexible laryngoscopy as indicated.

— Symptom review: pain, swallowing, voice, weight, breathing.

— Adherence to smoking/alcohol cessation, dental care.

— Baseline post-treatment imaging at 3 months (PET/CT or MRI/CT) to assess response. Negative PET highly predictive of durable control; positive findings need biopsy.

— Routine imaging after that is symptom-driven — no clear survival benefit to scheduled imaging in asymptomatic patients.

— Annual chest CT for surveillance of pulmonary mets and second primaries in heavy smokers.

— TSH every 6–12 months lifelong after neck RT.

— Plasma EBV DNA quarterly in nasopharyngeal carcinoma.

— CBC, CMP as clinically indicated.

— Speech-language pathology: swallowing therapy, voice rehab (TEP prosthesis training after laryngectomy).

— Physical therapy: neck/shoulder ROM after neck dissection (CN XI dysfunction → trapezius weakness).

— Lymphedema therapy: manual drainage, compression garments.

— Pain management: chronic neuropathic pain — gabapentinoids, duloxetine; opioid stewardship.

— Nutritional support: until PEG removable (typically when oral intake ≥80% of needs).

Board pearl: TSH must be checked every 6–12 months indefinitely in any patient who received neck RT — hypothyroidism develops in 30–50% and is reversible/treatable but easily missed.

Surveillance schedule (NCCN):

Each visit includes:

Imaging:

Laboratory monitoring:

Rehabilitation:

Psychosocial support: survivor support groups, counseling, return-to-work planning.

Ethical, Legal, and Patient Safety Considerations

— Total laryngectomy profoundly affects identity, voice, social function. Consent must include detailed discussion of voice loss, permanent stoma, alternative organ-preservation chemoRT (with comparable oncologic outcomes for many), and rehab options. Ideally involve voice rehab specialist and prior laryngectomee mentor pre-op.

— Chemoradiation toxicities (xerostomia, dysphagia, PEG dependency, ototoxicity, infertility risks with high-dose cisplatin) must be discussed; offer fertility preservation referral in reproductive-age patients before cisplatin.

— Patients with advanced disease and significant pain/opioid use, or with brain mets, may have fluctuating capacity. Document capacity assessment at major decision points; engage surrogate decision-makers (healthcare proxy, durable POA) early.

— Address goals of care early, not only at end of life. HNC has high symptom burden — pain, dysphagia, disfigurement, airway compromise.

— Document code status, DNR/DNI, healthcare proxy. Discuss the trajectory: progressive obstruction, bleeding, aspiration are foreseeable; POLST form when appropriate.

— Patients discharged on PEG-tube feeds, tracheostomy, or PICC chemo require coordinated home health, clear medication reconciliation, and follow-up phone call within 48–72 hours.

— Communicate "neck breather" status to all care teams — emergency airway is via stoma, not mouth. Patients should wear medical alert and have stoma cover.

— Reconcile opioids carefully — high overdose risk after RT mucositis resolves and pain drops.

Step 3 management: Before total laryngectomy, document a voice rehab consultation, prior-laryngectomee peer support discussion, and a detailed informed consent including discussion of organ-preservation chemoRT alternative — failure to discuss alternatives is a common malpractice trigger.

Informed consent for treatment-altering decisions:

Capacity and decision-making:

Advance care planning:

Transition-of-care risks (Step 3 favorite):

Ethics: futility and palliation: for incurable disease, integrate palliative care early; respect patient choice to decline aggressive therapy.

Mandatory reporting: intimate partner violence, suicidal ideation (elevated in HNC), elder abuse if applicable.

Public health: HPV vaccination uptake is a population-level intervention; advocate at every clinical encounter.

High-Yield Associations and Rapid-Fire Facts

Board pearl: Memorize the trio — smoking + alcohol (oral/larynx), HPV-16 (oropharynx), EBV (nasopharynx). These three associations dominate Step 3 HNC vignettes.

HPV-16 → oropharyngeal SCC (tonsil, base of tongue); p16+ on IHC; better prognosis.

EBV → nasopharyngeal carcinoma, especially in Southern Chinese/Southeast Asian patients; plasma EBV DNA tracks disease.

Tobacco + alcohol → synergistic risk for oral cavity, larynx, hypopharynx SCC.

Betel/areca nut → oral cavity SCC; oral submucous fibrosis.

Plummer-Vinson syndrome (iron deficiency + esophageal webs + dysphagia) → post-cricoid hypopharyngeal SCC in women.

Wood dust, leather, nickel → sinonasal adenocarcinoma.

Radiation exposure → salivary gland tumors, thyroid cancer.

Fanconi anemia, dyskeratosis congenita → early-onset HNSCC.

Erythroplakia > leukoplakia in malignant potential.

Persistent hoarseness >2 weeks in adult → laryngoscopy required.

Adult unilateral serous otitis → nasopharyngeal carcinoma until proven otherwise.

Cystic level II neck mass in adult → HPV+ oropharyngeal SCC metastasis.

Cranial nerve XII palsy + neck mass → skull base/hypoglossal canal invasion.

Horner syndrome + neck mass → sympathetic chain involvement (paratracheal/level VI or apical lung).

Trismus in HNC = pterygoid muscle invasion (locally advanced).

Vocal cord fixation = T3 laryngeal cancer.

ENE (extranodal extension) = automatically N3b in non-HPV disease; indication for adjuvant chemoRT.

Positive margins post-resection → adjuvant chemoRT (not RT alone).

DOI >5 mm upstages oral cavity tumors to ≥T2.

Bilateral tonsillectomy during workup for cervical SCC of unknown primary.

Hyperbaric O₂ for osteoradionecrosis.

Pilocarpine/cevimeline for post-RT xerostomia.

TheraBite for trismus.

First-line metastatic HNC: pembrolizumab ± chemo (CPS-guided).

Cetuximab + RT for cisplatin-ineligible patients.

Board Question Stem Patterns

Key distinction: "What's the next step?" questions hinge on FNA before excision for SCC nodes, laryngoscopy before imaging for hoarseness, and HPV/EBV testing on biopsy — these are the most common discriminators.

"55-year-old smoker with 6-week history of hoarseness; PE reveals fixed left vocal cord..." → laryngeal SCC; next step = direct laryngoscopy with biopsy and CT neck with contrast.

"42-year-old man, nonsmoker, with painless 3-cm cystic right level II neck mass for 2 months..." → HPV+ oropharyngeal SCC; next step = FNA with p16 testing (NOT excisional biopsy).

"38-year-old man of Southern Chinese descent with unilateral epistaxis, serous otitis media, and a neck mass..." → nasopharyngeal carcinoma; order MRI nasopharynx + nasopharyngoscopy with biopsy; check EBV serology and plasma EBV DNA.

"65-year-old with mandible pain and exposed bone 18 months after head/neck radiation..." → osteoradionecrosis; treat with pentoxifylline + vitamin E, hyperbaric O₂, conservative debridement.

"Post-laryngectomy patient in respiratory distress; nurse is bagging via face mask..." → ineffective; ventilate via stoma; consider stomal/laryngectomy tube replacement.

"Patient on cisplatin develops Cr 2.4, Mg 0.9..." → hold cisplatin, hydrate, replete electrolytes; transition to carboplatin or cetuximab.

"Adult develops oral leukoplakia with red speckled area..." → biopsy erythroplakia (highest malignant risk).

"Painless slow-growing parotid mass with facial nerve weakness..." → malignant parotid tumor; facial nerve palsy = malignant feature.

"3 months after chemoRT for oropharyngeal SCC, PET/CT shows no residual disease..." → continue surveillance; no further treatment.

"Adult with TSH 12 mIU/L 2 years after neck RT..." → RT-induced hypothyroidism; start levothyroxine.

"Smoker quit 5 years ago, age 60, 30 pack-years..." → eligible for annual low-dose chest CT lung cancer screening.

"Recurrent metastatic HNSCC, PD-L1 CPS 20..." → first-line pembrolizumab monotherapy.

"Patient declines total laryngectomy for T3 glottic cancer..." → offer concurrent chemoradiation for organ preservation.

One-Line Recap

Head and neck cancer — predominantly squamous cell carcinoma — should be suspected in any adult with persistent (>2 weeks) hoarseness, dysphagia, oral ulcer, unilateral serous otitis, or neck mass, particularly in smokers/drinkers (oral cavity, larynx), HPV-exposed patients (oropharynx), or EBV-endemic populations (nasopharynx), and is evaluated with flexible laryngoscopy, FNA of suspicious nodes (never excisional biopsy first), CT neck with contrast, and HPV/EBV testing on biopsy, then managed via a multidisciplinary tumor board with stage- and site-tailored surgery, chemoradiation, or both.

Board pearl: When the stem describes a persistent symptom in an at-risk adult, the right answer is almost always "refer for laryngoscopy and tissue diagnosis," not antibiotics, PPI trial, or reassurance.

Highest-yield rule: Adult neck mass >2 weeks = HNSCC metastasis until proven otherwise → FNA, not excision.

HPV-16 oropharyngeal SCC is rising and has better prognosis; HPV vaccination 9–26 (catch-up to 45) is the cornerstone of prevention.

Smoking cessation, alcohol moderation, dental clearance pre-RT, and lifelong TSH monitoring are the most-tested longitudinal management items.

Airway emergencies and carotid blowout in advanced/recurrent disease require ICU-level escalation; post-laryngectomy patients are neck breathers — ventilate via the stoma.

No general population screening exists (USPSTF I statement); case-finding through dental exams and prompt evaluation of red-flag symptoms is the practical strategy.

Step 3 emphasis: transitions of care (PEG, trach, home health), survivorship plans, secondary prevention, and shared decision-making for function-impacting surgeries like total laryngectomy define the Step 3 voice for this topic.