Head and Neck Cancer: Types, Symptoms, Staging and Treatment — Overview, Diagnosis & Treatment Options | MyMedicPlus

Head and neck cancers (HNC) encompass malignancies arising in the oral cavity, oropharynx, larynx, hypopharynx, nasopharynx, salivary glands, thyroid, and nasal/paranasal sinuses. Squamous cell carcinoma (HNSCC) accounts for over 90% of cases. Globally, HNC is the sixth most common cancer, with approximately 900,000 new diagnoses and 450,000 deaths annually (GLOBOCAN 2020). In the United States, about 68,000 cases are diagnosed per year. Traditionally, HNSCC was driven by tobacco and alcohol use in older males; however, HPV (human papillomavirus, predominantly HPV16)-associated oropharyngeal cancer has risen dramatically, now accounting for 70–80% of oropharyngeal HNSCC in Western countries and affecting younger, non-smoking men. HPV-positive oropharyngeal cancer has a markedly better prognosis than HPV-negative disease — 5-year survival of 80–90% vs 40–60%. Nasopharyngeal carcinoma (NPC) is epidemiologically distinct, linked to Epstein-Barr virus and common in Southeast Asia, Southern China, and North Africa.

Tobacco smoking — cigarettes, cigars, pipe, smokeless tobacco, and betel nut — is the dominant risk factor for HPV-negative HNSCC. The lifetime relative risk for heavy smokers is 5–25 times the baseline. Alcohol use is an independent risk factor and acts synergistically with tobacco: combined tobacco-alcohol use confers a 30-fold increase in risk over non-users. HPV-16 infection — acquired through oral-genital contact — is the primary driver of the oropharyngeal cancer epidemic; number of lifetime oral sex partners is the strongest behavioral risk factor. EBV (Epstein-Barr virus) is directly implicated in NPC pathogenesis; dietary factors (preserved salted fish) and EBV exposure in childhood are risk factors in endemic populations. Prolonged sun exposure is the dominant risk for cutaneous head and neck squamous cell and basal cell carcinoma of the lip and face. Occupational exposures to nickel, formaldehyde, and wood dust increase risk of nasal and sinonasal cancers. Prior radiation to the head and neck increases the risk of secondary salivary gland and thyroid cancers.

Symptoms depend on the primary site. Oral cavity cancer presents as a non-healing mucosal ulcer, white (leukoplakia) or red (erythroplakia) patch, or indurated submucosal mass on the tongue, floor of mouth, buccal mucosa, or lip; pain and difficulty chewing develop as tumors enlarge. Oropharyngeal cancer (tonsil, base of tongue) typically presents with ipsilateral sore throat, dysphagia, referred otalgia, or a painless neck mass — an HPV-positive tonsillar primary may present with a cystic neck node as the only finding. Laryngeal cancer presents with persistent hoarseness (glottic tumors detected early due to voice changes) or dysphagia and stridor (supraglottic tumors detected late). Nasopharyngeal carcinoma presents with neck mass, nasal obstruction, epistaxis, serous otitis media, diplopia, or facial numbness from cranial nerve involvement. Hypopharyngeal cancer presents late with dysphagia, weight loss, and neck mass. All HNSCC shares a risk for referred otalgia, trismus (jaw restriction), and dysphagia.

Tissue biopsy provides histological diagnosis; fine-needle aspiration (FNA) of neck nodes is the standard initial approach for cervical lymphadenopathy. Panendoscopy (laryngoscopy, esophagoscopy, bronchoscopy) evaluates mucosal extent and identifies synchronous primaries. CT neck/chest with IV contrast defines locoregional disease; MRI provides superior soft-tissue delineation, particularly for tongue base and parapharyngeal tumors. PET-CT is valuable for M-staging and identifying an occult primary in cervical lymphadenopathy with unknown primary. AJCC 8th edition TNM staging is used; the HPV status (p16 immunohistochemistry as surrogate) is now incorporated into the oropharynx staging system, creating separate staging tables for p16-positive and p16-negative OPC. Tumor HPV status, PD-L1 Combined Positive Score (CPS), and EBV serology (for NPC) are mandatory for treatment planning. Dental evaluation and nutritional assessment are essential before treatment.

Early-stage (T1–T2N0) HNSCC can be treated with surgery alone or radiation alone with equivalent outcomes. Transoral robotic surgery (TORS) and transoral laser microsurgery enable minimally invasive resection of oropharyngeal primaries. Locally advanced HNSCC (Stage III–IVA) is treated with concurrent cisplatin-based chemoradiation (high-dose cisplatin 100 mg/m² every 21 days or weekly cisplatin 40 mg/m²) as the standard of care per RTOG/MACH-NC data, achieving 5-year OS of 45–65%. Induction chemotherapy (TPF: docetaxel, cisplatin, 5-FU) is considered for very locally advanced or unresectable disease. Cetuximab (anti-EGFR) is used in cisplatin-ineligible patients. For recurrent/metastatic HNSCC, first-line pembrolizumab monotherapy (PD-L1 CPS ≥1) or pembrolizumab plus platinum/5-FU (any CPS) per KEYNOTE-048 is the current standard, achieving median OS of 13 months. Nivolumab is second-line post-platinum therapy per CheckMate-141. NPC is treated with concurrent cisplatin-radiation; gemcitabine-cisplatin is standard for recurrent/metastatic NPC.

Prognosis in head and neck squamous cell carcinoma (HNSCC) varies substantially by site, stage, and HPV status. HPV-positive oropharyngeal cancer has the most favorable prognosis: 5-year overall survival of 80–90% even with locally advanced disease, and clinical trials are investigating de-escalation of treatment intensity for this group. HPV-negative HNSCC at the same stage has 5-year survival of 40–60%. For oral cavity SCC, stage I achieves 80–90% 5-year survival with surgery; advanced stage III–IV falls to 40–65%. Laryngeal cancer has stage-dependent survival: glottic T1 disease treated with radiation achieves 90–95% local control; supraglottic T3–T4 disease has 5-year survival of 40–60%. Nasopharyngeal carcinoma treated with cisplatin-chemoradiation achieves 5-year survival of 80% for stage II–III and 60–70% for stage IV. Recurrent and metastatic HNSCC carries a poor prognosis: median overall survival is 10–13 months with pembrolizumab-based first-line therapy per KEYNOTE-048. Key prognostic factors include HPV/p16 status, TNM stage, perineural invasion, lymphovascular invasion, surgical margin status, extranodal extension of nodal metastases, and ECOG performance status. Long-term survivors require monitoring for treatment-related late effects: xerostomia, hypothyroidism, dysphagia, osteoradionecrosis, and risk of secondary cancers.

Tobacco cessation is the single most impactful preventive intervention for HPV-negative HNSCC — risk decreases with duration of cessation. HPV vaccination (Gardasil 9, targeting HPV 16/18/31/33/45/52/58) is recommended for all adolescents (9–14 years ideally, catch-up to age 26) and may be considered up to age 45; it is expected to significantly reduce the incidence of HPV-related oropharyngeal cancers over the coming decades. Alcohol consumption should be minimized. Oral cavity cancer screening by dentists — examination for leukoplakia, erythroplakia, and non-healing ulcers at routine dental visits — enables early detection. Sun protection (SPF 30+ lip balm, hats) reduces lip carcinoma risk. In NPC-endemic regions, EBV serology screening for at-risk populations (first-degree relatives of NPC patients) is practiced. Avoidance of betel nut use, particularly common in South and Southeast Asia, reduces oral and oropharyngeal cancer risk.

Any of the following persisting for more than 3 weeks warrants urgent referral to a head and neck specialist or ENT surgeon: unexplained hoarseness or voice change; difficulty or pain on swallowing; a non-healing ulcer in the mouth; a persistent neck mass or swelling; unexplained unilateral serous otitis media in an adult; unilateral nasal obstruction or epistaxis; or trismus. Do not attribute persistent hoarseness to 'laryngitis' without examination. A painless firm cervical lymph node in a male aged 30–60 (particularly involving the posterior triangle or jugulodigastric nodes) should be considered HPV-associated oropharyngeal primary until proven otherwise, and investigated with FNA and nasopharyngoscopy. NICE NG12 mandates urgent 2-week-wait referral for unexplained neck lump in adults or unexplained persistent sore throat.