Head and neck cancers

• Head and neck cancer is usually squamous cell carcinoma of the aerodigestive tract: mouth, throat, voice box, and the nasopharynx behind the nose.
• In the mouth, throat and larynx, tobacco and alcohol are the main causes; betel quid matters in South and Southeast Asia.
• Two viruses cause distinct forms: high-risk HPV (most often HPV 16) in the oropharynx, and Epstein-Barr virus in nasopharyngeal carcinoma.
• Warning signs are a lump in the neck, a mouth ulcer not healing after three weeks, persistent hoarseness, pain on swallowing, nosebleeds with nasal blockage, or one-sided ear symptoms.
• Diagnosis is by biopsy at panendoscopy, staged with CT/MRI and, in selected cases, PET-CT.
• Early disease is treated with one modality; locally advanced disease needs surgery plus adjuvant radiotherapy or primary chemoradiotherapy. Nasopharyngeal cancer is treated with radiotherapy and chemotherapy, not surgery.

By the end of this page you should be able to:

1. Classify head and neck squamous cell cancer by site and by cause (tobacco and alcohol, HPV, EBV).
2. Recognise the red-flag symptoms for each site and know the urgent referral thresholds.
3. Explain how panendoscopy, biopsy, p16 staining and imaging stage the disease, and how the TNM stage directs treatment.
4. Plan the management of early and locally advanced disease for the oral cavity, larynx and oropharynx, including neck dissection levels, cisplatin-based chemoradiotherapy, and larynx preservation.
5. Outline radiotherapy- and chemotherapy-based management of nasopharyngeal carcinoma.
6. Discuss functional outcomes, follow-up, prevention and low-resource practice.

Head and neck cancer is an umbrella term for malignant tumours of the upper aerodigestive tract, i.e. the airways and food passages from the lips to the windpipe and gullet entrance. Squamous cell carcinoma (SCC) is the dominant malignant type at these sites, so the terms are often used interchangeably. This page concentrates on mucosal SCC and nasopharyngeal carcinoma; salivary gland tumours, mucosal melanoma, thyroid cancer and lymphoma are mentioned only briefly in the differential. ^[2]

By site the disease splits into:

• Oral cavity cancer: lip, tongue, floor of mouth, buccal mucosa, hard palate, retromolar trigone and alveolus.
• Oropharyngeal cancer: base of tongue, tonsils, soft palate and pharyngeal walls.
• Laryngeal cancer: glottic (vocal cords), supraglottic and subglottic.
• Hypopharyngeal cancer: pyriform sinuses, post-cricoid region and posterior pharyngeal wall.
• Nasopharyngeal carcinoma (NPC): the space behind the nose (nasopharynx), an anatomically and biologically distinct disease.

Cause-based classification matters more for management:

• Tobacco- and alcohol-associated SCC of the oral cavity, larynx and hypopharynx.
• HPV-associated SCC, predominantly of the oropharynx, driven by high-risk HPV (most often HPV 16).
• EBV-associated NPC, the non-keratinizing type that predominates in endemic regions.

The fifth edition of the WHO Classification of Head and Neck Tumours divides NPC into keratinizing SCC, non-keratinizing carcinoma (differentiated and undifferentiated types) and the rare basaloid SCC. Non-keratinizing, EBV-driven disease is the form that dominates in East and Southeast Asia and is the focus of most NPC treatment protocols.

Head and neck SCC is a sizeable global problem. In 2020 an estimated 19.3 million new cancers were diagnosed and almost 10 million cancer deaths occurred worldwide; head and neck SCC (lip, oral cavity, larynx, oropharynx and hypopharynx, but excluding nasopharyngeal carcinoma) accounted for 3.9% of new cancer cases (744,994 cases) and 3.7% of cancer deaths (357,339 deaths).^[3]

About 80% of cases worldwide are attributable to tobacco use, excessive alcohol consumption or both. In South Asia, smokeless tobacco and betel quid/areca nut products dominate and drive very high rates of oral cavity cancer.^[3]

Nasopharyngeal carcinoma is rarer but geographically concentrated. About 120,000 new cases were diagnosed in 2022, with the burden concentrated in East and Southeast Asia and, within China, in the southern provinces. Age-standardized incidence and mortality have declined in many regions, but absolute case numbers are projected to rise. NPC is more common in men, and susceptibility persists in migrant populations and their descendants.^[5]

HPV-associated oropharyngeal SCC is the one subsite with rising incidence in many countries. An international registry analysis covering 42 countries found significant increases in oropharyngeal cancer in 19 countries among men and 23 among women, with incidence rates about three to fourfold higher in men. HPV 16 is the predominant genotype among the high-risk HPV types detected in oropharyngeal cancer.^[6]

Tobacco and alcohol. Tobacco (smoked and smokeless) and alcohol act synergistically. Heavy smoking with heavy drinking creates a field of mutated epithelium throughout the aerodigestive tract, explaining the high rate of second primary cancers.

Betel/areca nut. Chewing betel quid/areca nut, often with tobacco, is a leading cause of oral cavity cancer in India, Taiwan and parts of Southeast Asia. The quid keeps contact with the buccal mucosa for hours and is linked to oral submucous fibrosis.

HPV. High-risk HPV is an established causal driver of oropharyngeal SCC, usually HPV 16; HPV 33, 18, 35 and 58 are much less common. HPV-associated disease often presents in people without a heavy smoking or alcohol history and involves lymphoepithelial tonsillar crypt tissue.

EBV. EBV is closely associated with non-keratinizing NPC in endemic regions. Infection alone is not enough: host genetic susceptibility (HLA and other loci) plus environment, such as Chinese-style salted fish and other preserved foods, combine. Smoking shows a dose-response relationship with NPC risk in endemic areas.

Other exposures include preserved foods and selected occupational or inhalational agents. Advancing age, male sex and prior head and neck radiotherapy increase risk for several subsites.

Squamous carcinogenesis at these sites follows a sequence from normal epithelium through dysplasia to invasive carcinoma, usually with a visible premalignant phase. In the oral cavity, leukoplakia (a white patch that cannot be scraped off) and erythroplakia (a red patch) are the important warning lesions; erythroplakia carries a higher risk of dysplasia or invasive cancer. Field cancerization explains why these patients develop multiple primaries over time.

In HPV-driven disease, viral DNA integrates into tumour cells; viral oncogenes drive uncontrolled proliferation. HPV status is established by p16 overexpression on immunohistochemistry (IHC) and, when needed, HPV-specific DNA or RNA in-situ hybridisation.

In EBV-driven NPC, EBV persists in type II latency, expressing EBNA1, LMP1 and LMP2A and EBV-encoded non-coding RNAs. These products promote survival, growth and immune evasion. EBV exists as clonal episomes in tumour cells, implying infection occurs before clonal expansion.

Most lesions are invasive squamous cell carcinoma with keratin pearls and intercellular bridges on microscopy. In the oral cavity, tumour depth of invasion (DOI) measured in millimetres is a key pathologic variable, and the number of invaded nodes, extracapsular (extranodal) extension, perineural infiltration, lymphatic invasion and margin status must all be reported. An R0 resection is one with no residual tumour; the German S3 guideline standardises an R0 resection goal of at least 5 mm distance to the tumour margin.^[4]

NPC histology follows the WHO classification (keratinizing, non-keratinizing differentiated, non-keratinizing undifferentiated, basaloid). EBV is closely associated with the non-keratinizing forms.

A non-healing ulcer, a lump, or a red or mixed red-and-white patch are the classic warning signs. Pain, dysphagia, referred otalgia, loose teeth, paraesthesia of the lip or tongue, and trismus suggest advanced or invasive disease.

Persistent sore throat, odynophagia (pain on swallowing), dysphagia, a neck lump, voice change, referred otalgia, aspiration episodes, weight loss and haemoptysis. Hypopharyngeal tumours often present late because the hypopharynx is a wide, silent space.

Persistent unexplained hoarseness is the hallmark of glottic (vocal cord) tumours. Supraglottic tumours present with sore throat, dysphagia, aspiration and referred otalgia, often with a neck lump. Stridor signals airway obstruction.

NPC often presents late because the nasopharynx is hidden. Early symptoms are subtle: nasal obstruction or minor blood-stained nasal discharge. As the tumour grows, patients develop otologic symptoms (tinnitus, hearing loss, ear fullness, otitis media with effusion), because the pharyngeal opening of the Eustachian tube is affected; unilateral ear symptoms in an adult deserve vigilance. Painless cervical lymphadenopathy is one of the most common presenting features. Headache, diplopia and facial numbness suggest skull base or cranial nerve involvement, a feature of advanced disease with worse prognosis. About 10% of patients already have distant metastases (bone, lung, liver) at presentation.^[5]

Cervical lymphadenopathy can be the first sign of an oropharyngeal, hypopharyngeal or nasopharyngeal primary, including when the primary is hidden ("unknown primary"). Nodes are often firm, non-tender and progressive.

NICE's suspected cancer guideline (NG12, last updated April 2026) uses these referral thresholds:^[1]

• Laryngeal cancer: consider a suspected cancer pathway referral for people aged 45 or over with persistent and unexplained hoarseness, or an unexplained lump in the neck. ^[1]
• Oral cancer: consider a suspected cancer pathway in people with unexplained ulceration in the oral cavity lasting for more than 3 weeks, or a persistent unexplained lump in the neck; urgent dentist assessment is suggested for a lump on the lip or in the oral cavity, or a red or red-and-white patch (erythroplakia or erythroleukoplakia). ^[1]

A lump in the neck that is firm, progressive or persistent for several weeks, or any adult with unilateral nasal, otologic or cranial nerve symptoms plus a neck node, also needs urgent evaluation.

Diagnosis requires tissue. Clinical examination plus rigid head and neck endoscopy, followed by biopsy of the primary site. For mucosal disease, examination under anaesthesia with panendoscopy (inspection and biopsy of the nasopharynx, oropharynx, hypopharynx, larynx and oesophagus) maps the tumour and finds synchronous primaries due to field cancerization. Nomenclature for an occult primary includes guided biopsies, tonsillectomy and tongue-base mucosectomy.^[2]

• Head and neck contrast-enhanced CT or MRI to define tumour extent and nodal disease. MRI is superior for soft tissue and for skull base and nasopharyngeal evaluation.
• Chest imaging (CT or FDG-PET) for distant disease.
• FDG PET-CT as the first investigation to detect an unknown primary in metastatic nodal SCC of presumed upper aerodigestive origin, and to detect the primary or stage the disease. Consider narrow-band imaging endoscopy if PET-CT fails.^[2]
• Systemic staging is offered to all patients except those with T1N0 or T2N0 disease. FDG PET-CT is offered for T4 hypopharyngeal or nasopharyngeal cancers and for N3 disease; conventional imaging (for example, chest CT) is offered when PET-CT is not indicated.^[2]

• p16 immunohistochemistry is strongly recommended for oropharyngeal cancer and is regarded as positive only when there is strong nuclear and cytoplasmic staining in more than 70% of tumour cells. Confirmatory high-risk HPV DNA or RNA in-situ hybridisation is considered in p16-positive disease.^[2][6]
• For unknown primaries, p16 and Epstein-Barr-encoded RNA (EBER) are both recommended.^[3]
• EBV plasma DNA is used in NPC for screening in endemic regions, for response assessment and for risk stratification during and after treatment. In a prospective study of 20,174 asymptomatic individuals, repeated plasma EBV DNA testing with confirmatory endoscopy and MRI reached a sensitivity of 97.1% and specificity of 98.6%, and 71% of screen-detected NPC was stage I or II compared with 20% in a historical cohort.^[5] Plasma EBV DNA is not a stand-alone exclusion test, because early disease may be undetectable.
• PD-L1 testing is recommended for recurrent or metastatic disease, because it guides immunotherapy choice.

Head and neck SCC is staged by the UICC/AJCC TNM system. The EHNS-ESMO-ESTRO guidance recommends the 8th edition, whereas NICE NG36 (2016) is framed on the 7th edition. Nasopharyngeal carcinoma now uses the 9th edition of the AJCC/UICC TNM, which moves radiological extranodal extension into N3, consolidates non-metastatic disease into stages I to III and reserves stage IV for metastatic disease.^[3][2][5]

Simplified, T describes tumour size and extent (T1 to T4), N nodal involvement (N0 for none, N1 and above for affected nodes) and M distant metastasis (M0 none, M1 present). For oral cavity disease, depth of invasion modifies T. For the neck, extranodal (extracapsular) extension upstages nodal disease and is an indication for postoperative chemoradiotherapy.

Neck node levels (Robbins classification) guide selective and radical dissection and radiotherapy fields:

Oropharyngeal and hypopharyngeal primaries most often spread to levels II to IV; hypopharyngeal tumours may also involve level VI. The nodal ratio and distribution are part of clinical-pathological staging.

Management is a multidisciplinary team decision at a high-volume centre. Treatment should depend on stage, site, HPV and EBV status, swallowing and airway function, comorbidity and patient preference.^[3] These principles are also set out in the NICE, ESMO/EHNS and NCCN guidelines for head and neck cancer.^[1][2][7]

Early disease is treated as much as possible with a single modality. Locally advanced disease uses either surgery plus adjuvant chemoradiotherapy, or primary concomitant chemoradiotherapy. Postoperative radiotherapy should start within 6 weeks of surgery.^[3]

Oral cavity (T3/T4 or adverse pathology). Primary surgery followed by radiotherapy or chemoradiotherapy is preferred. Surgery includes resection with adequate margins and an elective neck dissection (levels IIa to IV ipsilaterally for lateralised T1 to T2 N0 tumours; bilateral levels IIa to IV when the tumour is close to the midline, at the soft palate or tongue base, or from T2).^[4]

Larynx. T1a glottic tumours are offered transoral laser microsurgery. T1b to T2 glottic tumours may be treated with transoral laser microsurgery or radiotherapy. T1b to T2 supraglottic tumours are offered transoral surgery or radiotherapy. For T3 tumours a choice is offered between radiotherapy with concomitant chemotherapy and surgery with adjuvant radiotherapy or chemoradiotherapy, with discussion of larynx preservation, risk of salvage laryngectomy and voice and swallowing function (including the need for a long-term feeding tube). For T4a disease, surgery with adjuvant radiotherapy, with or without concomitant chemotherapy, is considered.^[2]

Hypopharynx. Larynx-preserving treatment is offered when concurrent chemotherapy is suitable and there is no tumour-related dysphagia needing a feeding tube, compromised airway or recurrent aspiration pneumonia; otherwise primary surgery followed by adjuvant radiotherapy is offered.^[2]

Oropharynx (T1 to T2, N0). Patients are offered a choice of transoral surgical resection or primary radiotherapy. Postoperative radiotherapy, with or without concomitant chemotherapy, is considered where adverse risk factors (extranodal extension, positive margins, perineural or lymphatic invasion, more than one involved node, pT3 to pT4) are present.^[2][4]

HPV-positive oropharyngeal SCC. The treatment strategy should be the same as for HPV-negative disease. De-intensification of curative treatment should not be offered outside a clinical trial. HPV testing uses p16 IHC first, with HPV-specific testing in selected circumstances, including equivocal p16, discordance with morphology, low-prevalence regions, large multisite tumours, sites other than tonsil or base of tongue and trial requirements. The 2025 College of American Pathologists guideline defines p16 positivity as nuclear and cytoplasmic staining of at least moderate intensity in 70% or more of tumour cells.^[2][6]

Nasopharyngeal carcinoma. NPC is not treated with surgery as primary therapy. Intensity-modulated radiotherapy alone is standard for T1N0 disease; concurrent chemoradiotherapy is offered for stage 2 and above, with intensity-modulated radiotherapy with concomitant chemotherapy (NICE NG36). Induction chemotherapy with gemcitabine and cisplatin followed by chemoradiotherapy is widely used for higher-risk stage II and stage III disease; adjuvant capecitabine is used for selected high-risk patients. For recurrent or metastatic disease, platinum and fluorouracil plus cetuximab (standard if PD-L1-negative), or pembrolizumab with chemotherapy / monotherapy when PD-L1 is positive (CPS of 1 or more) are options, together with nivolumab after progression within 6 months of platinum.^[2][5]

The decision depends on nodal stage:

• cN0: selective neck dissection (levels as above), because an elective dissection is generally considered when the occult metastasis risk is 15 to 20%, and is standard for early oral cavity T1 to T2 (NICE offers sentinel lymph node biopsy unless cervical access is needed at the same time).^[2][4]
• cN1 to cN2a-c: selective or (modified) radical neck dissection.^[4]
• cN3: (modified) radical neck dissection where resectable.^[4]
• Modified radical dissection preserves one or more non-lymphatic structures (internal jugular vein, sternocleidomastoid muscle, accessory nerve) while removing levels I to V. Extended dissection removes additional structures. Accessory nerve preservation improves quality of life. At least 18 lymph nodes should be present in the specimen for an adequate dissection.^[4]
• After chemoradiotherapy, neck dissection is not recommended when post-treatment FDG PET-CT is negative and nodes are of normal size at 12 weeks; PET-CT is recommended 3 months after chemoradiotherapy for node-positive disease.^[3]

Radiotherapy for all patients should be delivered as intensity-modulated radiotherapy or volumetric modulated arc therapy. Concomitant chemoradiotherapy improves locoregional control and overall survival compared with radiotherapy alone. The standard chemotherapy is cisplatin at 100 mg per square metre on days 1, 22 and 43 of concomitant radiotherapy; weekly cisplatin at 40 mg per square metre is an alternative in the postoperative setting. In patients unfit for cisplatin, carboplatin plus 5-fluorouracil, cetuximab with radiotherapy or hyperfractionated/accelerated radiotherapy without chemotherapy are alternatives. Cetuximab with radiotherapy is an option when platinum is contraindicated in patients with a Karnofsky score of 90% or more. For hypoxia, a hypoxic radiosensitiser may be considered where available.^[3][4][2]

For larynx preservation, TPF (docetaxel, cisplatin, fluorouracil) induction chemotherapy for up to three courses according to response, followed by radiotherapy alone, is a validated option. Induction chemotherapy is otherwise not routinely recommended. Recurrent or metastatic terms include PD-L1-positive tumours (combined positive score of 1 or more): pembrolizumab monotherapy or pembrolizumab plus platinum and fluorouracil; nivolumab for progression within 6 months of platinum; cetuximab plus platinum-based chemotherapy for oral cavity primaries.^[3][2]

Treatment commonly affects swallowing, speech, voice, airway and shoulder function. Functional planning is part of the choice between surgery and chemoradiotherapy. After CRT, response assessment and neck management are guided by FDG PET-CT; NICE gives specific rules for oropharyngeal and hypopharyngeal or laryngeal primaries, generally 3 to 6 months after treatment in higher-risk nodal disease.^[2]

Follow-up should include clinical examination with flexible endoscopy every 2 to 3 months for the first 2 years, every 6 months for years 3 to 5 and annually thereafter; imaging is performed when symptoms or examination suggest recurrence. FDG PET-CT is recommended 3 months after chemoradiotherapy for node-positive disease.^[3]

Tumour complications include airway obstruction, major bleeding, cachexia, aspiration pneumonia and distant spread. Treatment complications include mucositis, xerostomia, dysphagia, osteoradionecrosis, laryngeal oedema, hypothyroidism, lymphoedema, wound and flap problems, shoulder dysfunction after accessory nerve injury, and cranial nerve or sensory deficits. Late toxicity of CRT includes fibrosis, dysphagia requiring long-term enteral feeding and second primary cancers in the irradiated field. Psychosocial and body-image effects are significant and should be anticipated.

Prognosis depends on site, stage at presentation, HPV and EBV status, performance status and comorbidity. In the modern era, most T1 to T2 disease treated with one modality has good locoregional control. The TNM stage drives both prognosis and treatment intensity. HPV-associated oropharyngeal SCC differs biologically from HPV-negative disease and, in most series, has a more favourable prognosis, but HPV status alone is not a reason to de-intensify curative treatment outside trials. NPC prognosis is stage-adapted and improved by the move to intensity-modulated radiotherapy with chemotherapy; plasma EBV DNA provides prognostic information before and during treatment, although it has not yet been written into TNM-9. Late distant failure (bone, lung, liver) is the main mode of death in endemic NPC.

• Stop tobacco and reduce alcohol; betel/areca habit cessation is essential in South Asia.
• Maintain good dental health and treat suspicious oral lesions early; erythroplakia and high-risk leukoplakia should be biopsied.
• HPV vaccination reduces high-risk HPV infection and is recommended in national programmes; any impact on oropharyngeal cancer incidence will take decades to appear.
• In high-risk (endemic) regions, plasma EBV DNA screening of middle-aged adults, with endoscopy and MRI for screen-positive individuals, can detect NPC earlier. There is no validated population-based screening for HPV-associated oropharyngeal cancer and no recognised precursor lesion.
• Refer suspicious lesions promptly: a mouth ulcer present for more than 3 weeks and persistent hoarseness in a person 45 or over are urgent referral flags.

• Comorbidity and older adults: fitness for cisplatin (renal, auditory and performance status) determines whether carboplatin, cetuximab or altered fractionation is used.
• Children and young adults with NPC: predominantly non-keratinizing, often locally advanced, but generally respond well to chemoradiotherapy; survivorship and late toxicity need attention.
• Unknown primary in the neck needs a prompt search with PET-CT and directed tissue sampling, because treatment (neck dissection with adjuvant (chemo)radiotherapy or primary (chemo)radiotherapy with surgery for persistent disease) differs from that for a known primary.

• Visual inspection of the oral cavity by trained workers can identify suspicious lesions; a mouth ulcer persisting beyond 3 weeks or erythroplakia needs urgent referral for biopsy.
• Flexible nasendoscopy and CT of the head and neck are the realistic minimum staging tools where available; PET-CT is often not.
• Radiotherapy with intensity modulation may be unavailable; conventional techniques and cisplatin (generic, low cost) remain the backbone. Avoid delaying referral to centres with oncology and radiotherapy services.
• Betel and smokeless tobacco cessation programmes are cheap and high-impact.
• In endemic NPC regions, plasma EBV DNA testing plus directed endoscopy can rationalise referrals where MRI and PET are scarce.

• Most head and neck cancers are squamous cell carcinomas of the oral cavity, oropharynx, larynx and hypopharynx, or nasopharyngeal carcinoma.
• Tobacco and alcohol together account for about 80% of cases worldwide; betel and areca nut are dominant in South Asia.
• High-risk HPV (most often HPV 16) drives oropharyngeal SCC; EBV drives nasopharyngeal carcinoma.
• Red flags include a mouth ulcer for over 3 weeks, erythroplakia, hoarseness persisting in a person 45 or over, a firm or growing neck lump and unilateral nasal, ear or cranial nerve symptoms.
• Diagnosis requires biopsy at panendoscopy; staging uses MRI or CT of the head and neck plus chest imaging; FDG PET-CT is reserved for T4 hypopharynx or nasopharynx, N3 disease and unknown primaries.
• HPV status in oropharyngeal cancer is assessed by p16 IHC, positive when more than 70% of tumour cells show strong nuclear and cytoplasmic staining, with HPV-specific testing in selected situations; EBV is assessed by EBER and plasma EBV DNA.
• Early disease is treated with one modality; locally advanced disease needs surgery plus adjuvant radiotherapy (with chemotherapy for extranodal extension or positive margins) or primary chemoradiotherapy.
• Larynx-preserving treatment integrates speech and swallowing outcomes and uses induction chemotherapy with TPF for appropriate T3 tumours.
• Concurrent cisplatin (100 mg per square metre on days 1, 22 and 43) plus intensity-modulated radiotherapy is standard chemoradiotherapy; cetuximab is an option when platinum is contraindicated in fit patients. ^[3]
• Nasopharyngeal carcinoma is radiotherapy-based, using concurrent chemoradiotherapy for stage 2 and above, sometimes with induction chemotherapy.
• Neck dissection is guided by the Robbins levels; selective dissection for cN0, (modified) radical for advanced nodal disease; aim for at least 18 nodes in a therapeutic specimen.
• Follow-up uses endoscopy every 2 to 3 months for 2 years, then every 6 months to 5 years, with annual review thereafter.

• Oral cavity and lip cancers
• Oropharyngeal cancer and HPV
• Laryngeal and hypopharyngeal cancer
• Nasopharyngeal carcinoma
• Cervical lymphadenopathy and metastatic neck disease
• Dysphagia and odynophagia
• Radiotherapy principles