Head and Neck Cancer

Squamous cell carcinomas of the oral cavity, oropharynx, larynx, hypopharynx, and nasopharynx — HPV status, EBV association, organ preservation, and the immunotherapy revolution in recurrent/metastatic disease

Key Points

Epidemiology and Classification

Head and neck cancers (HNC) encompass malignancies arising from the mucosal surfaces of the upper aerodigestive tract. In the United States, approximately 66,000 new cases are diagnosed annually, with a male-to-female ratio of approximately 2.5:1. Globally, HNC is the sixth most common cancer, with approximately 890,000 new cases per year. **Anatomic Sites and Distinct Biology:** **Oral Cavity:** Includes lip, anterior tongue (oral tongue; anterior 2/3), floor of mouth, buccal mucosa, hard palate, upper and lower alveolar ridges, and retromolar trigone. Predominantly driven by tobacco…

Oral Cavity Cancer

Oral cavity squamous cell carcinoma (OSCC) is the most common HNC site in low-income countries (driven by tobacco, areca nut/betel quid) and remains common in tobacco/alcohol-exposed populations worldwide. **Key clinical features:** - **Oral tongue (anterior 2/3):** Most common oral cavity subsite in Western countries. Presents as a non-healing ulcer, exophytic mass, or white/red mucosal lesion (leukoplakia or erythroplakia, which have premalignant potential). Lateral border of the tongue is the most common location. - **Floor of mouth:** Second most common. Close proximity to Wharton's duct…

Oropharyngeal Cancer — HPV+ vs HPV−

The oropharynx has undergone a paradigm shift over the past two decades. In the United States, HPV-related oropharyngeal squamous cell carcinoma (OPSCC) now accounts for >75% of oropharyngeal cancers and is projected to be the most common HPV-related cancer in American men — surpassing cervical cancer in absolute incidence. **HPV Biology in OPSCC:** - **HPV16** accounts for >90% of HPV-positive OPSCC. HPV18, 31, and 33 account for most of the remainder. - Mechanism: HPV E6 oncoprotein degrades TP53; E7 inactivates Rb → uncontrolled cell cycle entry. - **p16 immunohistochemistry** (strong,…

Nasopharyngeal Carcinoma (NPC)

Nasopharyngeal carcinoma (NPC) is epidemiologically and biologically distinct from other HNSCCs. It is the most common cancer in southern China (incidence 20–50/100,000 in Guangdong province), with elevated incidence also in Southeast Asia, North Africa, and among Indigenous Arctic peoples. In these endemic regions, virtually all NPC is EBV-associated. **WHO Classification:** - **Type I (Keratinizing SCC):** Rare in endemic regions; EBV-negative; related to tobacco; behaves like conventional HNSCC; poorer prognosis. - **Type II (Non-keratinizing SCC):** Intermediate; may be EBV-associated. -…

Hypopharyngeal Cancer

Hypopharyngeal squamous cell carcinoma carries the **worst prognosis** of all HNSCC sites, with 5-year overall survival of approximately 30–35% for all stages combined. The hypopharynx — comprising the pyriform sinuses, posterior pharyngeal wall, and postcricoid region — is a functionally silent area where tumors often grow to a large size before symptoms develop. **Epidemiology and Risk Factors:** - Strongly linked to tobacco and alcohol; male predominance (6:1). - Plummer-Vinson syndrome (iron-deficiency dysphagia with esophageal webs) is a rare predisposing condition, specifically for…

Laryngeal Cancer

Laryngeal cancer has been declining in incidence in the United States (reflecting decreased tobacco use) but remains one of the most common HNC sites globally. Approximately 70% of laryngeal cancers arise at the glottis (true vocal cords), 25% at the supraglottis, and <5% at the subglottis. **Clinical Presentation by Subsite:** - **Glottic:** Persistent hoarseness is an early symptom due to direct cord involvement; even T1 tumors alter voice quality. This early warning sign leads to earlier diagnosis and better prognosis. 5-year OS for T1 glottic: ~90%. - **Supraglottic (epiglottis,…

Oral Tongue and Base of Tongue Cancer

Although both anatomically defined as "tongue," **oral tongue** (anterior 2/3) and **base of tongue** (BOT; posterior 1/3, part of the oropharynx) are biologically and clinically distinct entities with different risk factors, staging systems, and treatment approaches. **Oral Tongue Cancer:** - Predominantly tobacco/alcohol-related; HPV is not a significant driver. - Most common site: lateral border of the oral tongue. - Depth of invasion (DOI) is the single most important predictor of nodal metastasis and survival — now incorporated into AJCC T-staging (see Oral Cavity section). - High-risk…

Salivary Gland Tumors

Salivary gland tumors arise from the major glands (parotid, submandibular, sublingual) and from minor salivary glands distributed throughout the upper aerodigestive tract mucosa. Unlike mucosal HNSCC, salivary gland malignancies constitute a histologically diverse group with distinct molecular drivers and clinical behaviors. **Epidemiology:** ~8,000 cases/year in the United States. 80% arise in the parotid, 10–15% in the submandibular gland, and 5–10% in minor salivary glands or the sublingual gland. Parotid tumors are benign in ~80% of cases (pleomorphic adenoma is the most common benign…

Staging — AJCC 8th Edition Key Changes

The AJCC 8th edition (implemented January 2018) introduced several critical changes specific to head and neck cancer: **Oropharyngeal Cancer — Two Separate Staging Systems:** - The 8th edition created entirely separate T/N/M and stage group tables for **p16-positive** (HPV-driven) and **p16-negative** oropharyngeal SCC. - p16+ OPC: N-stage is simplified; N1 = ≤4 ipsilateral nodes, all <6 cm; N2 = ≥5 ipsilateral nodes or bilateral nodes, all <6 cm; N3 = any node ≥6 cm. The favorable biology means the same anatomic extent of nodal disease is staged at a lower group. - p16− OPC: Staged…

Radiation Therapy Principles

Radiation therapy is a cornerstone of HNC treatment, used in definitive, adjuvant, and palliative settings. IMRT (intensity-modulated radiation therapy) is now the standard technique for all HNC sites requiring RT, replacing 3D-CRT and older techniques. **IMRT Principles:** - Allows dose painting: simultaneous integrated boost (SIB) technique delivers different doses to different target volumes in the same treatment course (e.g., 70 Gy/33 fx to gross tumor, 63 Gy/33 fx to high-risk subclinical disease, 57 Gy/33 fx to elective neck). - Critical benefit: **spares parotid glands** (reducing…

Systemic Therapy — Locally Advanced and Recurrent/Metastatic Disease

**Concurrent Chemotherapy — Locally Advanced HNSCC:** **Cisplatin 100 mg/m² every 3 weeks × 3 cycles** concurrent with RT remains the standard for locally advanced HNSCC wherever cisplatin is tolerable (PS 0–1, adequate renal function, no significant hearing loss, no neuropathy). The Meta-Analysis of Chemotherapy in Head and Neck Cancer (MACH-NC; updated 2009) confirmed a 6.5% absolute 5-year OS benefit with concurrent chemotherapy added to RT. **Weekly cisplatin (40 mg/m²):** Commonly used alternative; broadly equivalent efficacy with potentially lower acute toxicity profile and higher RT…

Nutritional, Functional, and Quality-of-Life Considerations

Head and neck cancer treatment carries a uniquely high burden of functional morbidity because the anatomic region governs speech, swallowing, taste, saliva production, hearing, and cosmesis — fundamental to daily human interaction and quality of life. **Xerostomia (Dry Mouth):** Xerostomia from parotid irradiation is the most common long-term toxicity of HNC radiotherapy, affecting >70% of patients treated with conventional RT. IMRT significantly reduces xerostomia by limiting mean parotid dose to 60 Gy to mandible, dental extractions after RT, poor dental hygiene, smoking, diabetes.…

Surveillance and Survivorship

**Post-Treatment Surveillance Schedule (NCCP/NCCN Framework):** - **History and physical exam (including flexible nasopharyngoscopy/laryngoscopy):** Every 1–3 months for year 1; every 2–4 months year 2; every 4–6 months years 3–5; annually thereafter. - **Imaging:** Baseline post-treatment PET-CT or contrast-enhanced CT/MRI at 3 months after completion of definitive therapy for locally advanced disease. Additional cross-sectional imaging directed by clinical findings. Routine surveillance PET-CT at 3 months post-CRT has high sensitivity for residual disease (complete metabolic response →…