Head-and-neck squamous-cell cancer

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

Head and neck squamous cell cancer comprises mucosal cancers of the oral cavity, oropharynx, hypopharynx and larynx; nasopharyngeal disease has distinct EBV-associated biology and treatment. Tobacco and alcohol remain major causes, while HPV now accounts for many oropharyngeal cancers. A small primary may first appear as a painless cystic cervical node. Persistent unilateral symptoms and a normal cursory mouth examination should therefore lead to flexible endoscopy and specialist imaging rather than repeated antibiotics.

Diagnosis should establish site, subsite, histology, HPV relevance, local extent, nodal stage and distant disease while preserving future treatment. Ultrasound-guided needle sampling is preferred for a neck mass; an open biopsy can contaminate tissue planes and complicate definitive neck treatment. MRI is particularly useful for tongue, skull-base, perineural and marrow detail, while contrast CT gives rapid airway, cartilage, node and chest information. PET-CT answers selected staging and occult-primary questions but inflammation can cause false-positive uptake.

Curative choice balances disease control and function. Early lesions often require a single modality. Advanced oral cavity cancer is commonly resected with neck management and reconstruction, whereas organ-preserving chemoradiotherapy is central for many pharyngeal and laryngeal tumours. Positive margins or extranodal nodal extension may indicate postoperative cisplatin chemoradiotherapy. Fitness is not captured by age alone: kidney function, audiometry, neuropathy, nutrition and ability to attend and tolerate radiotherapy determine whether cisplatin is appropriate.

Support is longitudinal. Pretreatment dental intervention reduces later osteoradionecrosis, prophylactic swallowing work limits disuse, and dietetic support prevents avoidable interruption. During therapy, clinicians must actively manage mucositis, pain, secretions, candidiasis, dehydration, electrolyte loss and aspiration. After treatment, surveillance examines for recurrence and second primaries while treating xerostomia, fibrosis, lymphoedema, thyroid dysfunction, hearing loss and psychosocial consequences.

Key points

Persistent unexplained oral ulceration, unilateral throat symptoms, hoarseness, dysphagia, referred otalgia or adult neck lump requires urgent head-and-neck assessment; pain is not required.
First-line specialist assessment is full oral and neck examination plus flexible nasendoscopy; image and sample a suspicious node without proceeding to an unplanned open neck biopsy.
Ultrasound-guided fine-needle aspiration is often the first nodal sample; core biopsy is useful when cytology is non-diagnostic or lymphoma is possible.
The diagnostic reference standard is adequate histology from the primary or metastatic node, with p16 testing for oropharyngeal squamous cancer and other site-directed viral testing when appropriate.
Contrast CT or MRI defines local and nodal anatomy; PET-CT is used for selected advanced staging, an occult primary and post-chemoradiotherapy response assessment.
Do not begin treatment before airway, dental, nutrition, speech-and-language, hearing, renal, performance and psychosocial assessment have been integrated by the specialist MDT.
Early disease may be treated with one modality, usually transoral or open surgery or radiotherapy; locally advanced disease commonly needs surgery plus risk-adapted adjuvant therapy or definitive chemoradiotherapy.
Cisplatin is a key radiosensitiser for eligible patients, but renal impairment, hearing loss, neuropathy and frailty may make another regimen or radiotherapy alone safer.
HPV-positive oropharyngeal cancer has a better average prognosis, but smoking history, anatomical stage and patient factors still matter and HPV status does not justify off-protocol de-escalation.
Rehabilitation, smoking and alcohol support, oral care, swallowing exercises and late-effect surveillance are components of cancer treatment, not optional extras.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Tobacco and alcohol

Cumulative tobacco exposure is the principal preventable cause across oral, laryngeal and hypopharyngeal sites; alcohol acts independently and synergistically by increasing mucosal carcinogen exposure.

Oncogenic human papillomavirus

Transcriptionally active high-risk HPV, especially HPV16, drives a biologically distinct group of oropharyngeal cancers often presenting with a cystic neck node.

Site-specific infection and exposure

Epstein–Barr virus is strongly linked to nasopharyngeal carcinoma, while betel-quid chewing, poor oral health and occupational exposures contribute in particular populations.

Field and host susceptibility

Prior head-and-neck cancer, radiotherapy, immunosuppression and rare inherited DNA-repair disorders increase risk; continued smoking raises second-primary and treatment-toxicity risk.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Squamous dysplasia becomes invasive
Repeated carcinogen injury accumulates TP53 and cell-cycle abnormalities, allowing mucosal dysplasia to cross the basement membrane and invade muscle, cartilage, bone and nerves.
2
HPV disrupts tumour suppressors
Viral E6 and E7 proteins inactivate p53 and retinoblastoma pathways; p16 overexpression is a useful surrogate in the appropriate oropharyngeal setting.
3
Lymphatic spread is orderly but early
Rich cervical lymphatics allow nodal metastasis before the primary is obvious; node level and laterality reflect site-specific drainage and affect treatment fields.
4
Treatment affects shared functions
Tumour and therapy involve airway, speech, swallowing, salivary glands, taste, dentition and thyroid, so organ preservation must include function rather than anatomy alone.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Oral cavity lesion

A non-healing ulcer, indurated patch, unexplained tooth mobility, bleeding, tongue fixation or sensory change is suspicious even without pain.

Oropharyngeal presentation

Unilateral sore throat, dysphagia, tonsillar asymmetry, referred otalgia or a cystic level II neck node may represent HPV-related disease.

Hypopharyngeal disease

Progressive dysphagia, aspiration, weight loss, otalgia and late neck nodes are typical because early lesions can be clinically hidden.

Nodal presentation

A persistent firm or cystic adult neck mass is metastatic cancer until adequately assessed, particularly when it enlarges or lacks infective features.

Skull-base or neural invasion

Trismus, facial numbness, tongue weakness, Horner syndrome or multiple cranial neuropathies indicates advanced perineural or skull-base spread.

Airway or bleeding emergencyRed flag

Stridor, secretion intolerance, rapid respiratory fatigue or sentinel tumour bleeding requires immediate multidisciplinary rescue rather than routine clinic investigation.

Red flags requiring action

Stridor, drooling, tripod posture, cyanosis, exhaustion or reduced consciousness indicates critical upper-airway obstruction.
Persistent unexplained neck lump, oral ulcer, unilateral throat pain, dysphagia, odynophagia, hoarseness or referred otalgia requires urgent cancer assessment.
A pulsatile sentinel bleed from mouth, neck wound or tracheostomy can precede carotid blowout and needs immediate specialist haemorrhage planning.
Trismus, cranial-nerve deficit, Horner syndrome, fixed nodal disease or severe deep pain suggests skull-base, neural or carotid-space invasion.
Weight loss, dehydration, aspiration, recurrent chest infection or inability to swallow medication requires same-day nutritional and airway assessment.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
First-line examination and flexible nasendoscopyFirst stepFirst line
Why
Inspect all accessible mucosa, vocal-cord movement and the upper airway and identify a primary or synchronous lesion.
Interpretation and limitations
Document site, size, laterality, fixation, trismus, cranial nerves and all neck levels; a normal endoscopy does not exclude an occult tonsil or tongue-base primary.
02
First-line ultrasound-guided nodal samplingFirst line
Why
Obtain cytology from a suspicious cervical node while defining its solid, cystic and vascular features.
Interpretation and limitations
Use core biopsy when FNA is non-diagnostic or lymphoma is possible; send material for appropriate immunocytochemistry and HPV or EBV-related testing through pathology.
03
Reference-standard tissue histology
Why
Confirm invasive squamous carcinoma and obtain site-appropriate biomarker information.
Interpretation and limitations
Biopsy the primary under local or general anaesthesia when safe; p16 immunohistochemistry stages oropharyngeal SCC but is not a universal surrogate at other sites.
04
Contrast CT neck and chest
Why
Stage primary, cervical nodes, airway, vessels and thoracic metastasis or second primary and plan biopsy and treatment.
Interpretation and limitations
Assess cartilage, bone, extranodal extension and carotid relation; inflammatory nodes can mimic metastasis and small mucosal disease may be occult.
05
MRI primary site
Why
Define soft-tissue, tongue, marrow, skull-base and perineural spread where these change resection or radiotherapy fields.
Interpretation and limitations
MRI complements rather than automatically replaces CT and requires a protocol matched to the anatomical subsite.
06
PET-CT for selected staging or occult primary
Why
Search for an occult mucosal primary, distant disease or synchronous cancer and assess response after definitive chemoradiotherapy.
Interpretation and limitations
Obtain before disruptive biopsy when feasible in occult-primary work-up; interpret post-treatment scans at the recommended interval because early inflammation is avid.
07
Pretreatment functional assessment
Why
Determine whether planned surgery, radiotherapy and systemic therapy can be delivered safely.
Interpretation and limitations
Include dental review, dietitian, speech and language therapy, weight, swallowing, kidney function, magnesium, audiometry, neuropathy and performance status before cisplatin-based treatment.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Reactive or infective disease

Dental sepsis, tonsillitis, tuberculosis and deep-neck infection can cause pain, ulceration and nodes, but persistence, firmness or necrosis requires tissue diagnosis.

Lymphoma

Rubbery nodes, systemic symptoms or bulky Waldeyer-ring tissue can represent lymphoma; core tissue and flow cytometry are preferable to an unplanned open excision.

Salivary or thyroid malignancy

Parotid, submandibular and thyroid primaries produce site-specific masses and different cytology, staging and surgical pathways from mucosal squamous cancer.

Benign mucosal and neural disease

Traumatic ulcer, reflux, candidiasis and neuralgia may mimic symptoms, but an unexplained lesion or unilateral symptom that persists despite treatment still needs direct examination.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01Urgent presentationProtect airway and circulation firstFirst stepThe patient has stridor, secretion intolerance, respiratory fatigue, expanding swelling or major bleeding.

1Call senior anaesthesia and head-and-neck surgical teams and move to a monitored area while keeping the patient upright, calm and oxygenated with suction available.
2Agree a primary airway or haemorrhage plan and a failed-plan rescue before sedation, transfer or instrumentation; use theatre and interventional radiology support where indicated.
3DefinitiveAfter physiological control, obtain targeted imaging and biopsy without delaying definitive airway, embolisation, surgery, antibiotics or transfusion required for the emergency.

02Neck lumpDiagnose without compromising the neckAn adult has a persistent unexplained cervical node, including an apparently cystic node.

1Perform complete head-and-neck examination and flexible nasendoscopy and arrange ultrasound with needle sampling through the rapid-access cancer pathway.
2Use cross-sectional imaging and adequate cytology or core tissue with site-directed HPV or EBV work-up; do not assume a cystic result is benign in an adult.
3DefinitiveIf no primary is found, complete specialist occult-primary assessment, often including PET-CT and examination under anaesthesia, before definitive neck treatment; avoid unplanned open biopsy.

03Curative treatmentChoose modality by site, stage and functionStaging shows potentially curable mucosal squamous cancer.

1Discuss at the specialist MDT with surgical, radiation, medical oncology, radiology, pathology, restorative dental, dietetic and speech-and-language input.
2Use a single modality for suitable early disease and combined treatment for higher-risk disease, selecting surgery, neck dissection, radiotherapy and cisplatin according to subsite and pathological risk.
3Record airway, nutrition, dental, hearing, renal and rehabilitation plans before treatment and review toxicity weekly so mucositis or dehydration does not cause avoidable interruption.

04Recurrent or metastaticRe-biopsy and align systemic treatment with goalsDisease is unresectable, recurrent after prior treatment or metastatic.

1Confirm recurrence when feasible and restage, reviewing prior radiotherapy fields, platinum exposure, PD-L1 testing, performance, symptoms and potentially salvageable local disease.
2Offer funded immunotherapy, platinum-based treatment, radiotherapy, surgery or best supportive care according to current indication and individual benefit rather than a remembered universal sequence.
3Integrate pain, nutrition, airway, bleeding, secretion and psychological care early and define response and stopping criteria before treatment begins.

Key medicines and prescribing safety3 treatments · regimens, roles and cautions

Improves locoregional control when added to radiotherapy for appropriately selected high-risk or locally advanced squamous cancer.

Cisplatin with radiotherapy

A common definitive or postoperative radiosensitising protocol gives cisplatin 100 mg/m² intravenously on radiotherapy days 1, 22 and 43; some specialist protocols use 40 mg/m² weekly. Use the exact local regimen and eligibility criteria.

Provide protocol hydration and antiemesis and monitor creatinine clearance, magnesium, marrow, hearing, neuropathy and performance; do not casually substitute schedules or continue through clinically important renal or auditory toxicity.

Provides PD-1 blockade for selected recurrent or metastatic head-and-neck squamous cancer.

Pembrolizumab

Use the licensed fixed intravenous schedule, commonly 200 mg every 3 weeks or 400 mg every 6 weeks, alone or with protocol chemotherapy only when the recurrent or metastatic indication and current NICE biomarker criteria are met.

Check prior transplant and autoimmune disease and monitor for pneumonitis, colitis, hepatitis, nephritis, myocarditis and endocrine or neurological toxicity; new deterioration requires infection and progression assessment as well as immune-toxicity treatment.

Treats persistent nociceptive pain from mucosal, bone or soft-tissue invasion while local and neuropathic measures are arranged.

Morphine for severe cancer pain

For an opioid-naive adult able to swallow, a cautious starting regimen is immediate-release oral morphine 2.5 to 5 mg every 4 hours with the same dose as needed for breakthrough, titrated to response before conversion to modified release.

Prescribe laxative and antiemetic when indicated, review sedation and respiratory risk and adjust for renal impairment; route may need changing with dysphagia or mucositis, and escalating pain warrants structural reassessment.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Airway obstruction and aspiration

Primary tumour, nodal compression, oedema or bilateral vocal-cord dysfunction can obstruct the airway, while impaired laryngeal closure causes aspiration pneumonia.

Malnutrition and dehydration

Pain, trismus, dysgeusia, mucositis and dysphagia reduce intake and can interrupt curative radiotherapy unless dietetic and swallowing support begins early.

Major haemorrhage

Tumour invasion, infection, fistula and previous surgery or radiotherapy can erode carotid branches, producing sentinel bleeding followed by catastrophic haemorrhage.

Late treatment morbidity

Xerostomia, dental decay, osteoradionecrosis, fibrosis, lymphoedema, hypothyroidism, hearing loss and chronic dysphagia may persist years after cure.

Recurrence and second primary cancer

Local, nodal and distant relapse remain possible, while tobacco-related field cancerisation increases new lung, oesophageal and head-and-neck primaries.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

During radiotherapy or chemoradiotherapy, review weight, intake, swallowing, mucositis, skin, secretions, pain, hydration, renal function, electrolytes, infection and airway at least weekly.
Monitor feeding-tube or tracheostomy sites and preserve oral intake and swallowing exercises whenever safe to reduce disuse-related dysfunction.
After curative treatment, use scheduled clinical examination and flexible endoscopy, with imaging directed by site, response protocol and new symptoms rather than reassurance from a single scan.
Check thyroid function after neck irradiation and assess hearing, dental health, salivary function, fibrosis, lymphoedema, speech and aspiration over the long term.
Continue tobacco and alcohol support and investigate lung, oesophageal or new mucosal symptoms promptly because second primary cancer risk persists.
For systemic therapy, record response, performance, organ toxicity and patient-defined benefit at each cycle and stop treatment that is harmful without meaningful control.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

Cystic does not mean benign

An HPV-related oropharyngeal metastasis may be a smooth cystic neck mass, so adult lateral-neck cysts require malignancy assessment before excision.

Open biopsy can cause harm

Unplanned node excision can disrupt tissue planes and complicate subsequent neck dissection or radiotherapy; needle diagnosis and complete staging should come first.

Referred otalgia is anatomical

A normal ear with persistent unilateral pain may reflect glossopharyngeal or vagal referral from pharyngeal or laryngeal tumour.

HPV is site specific

p16 is prognostic and staging-relevant in oropharyngeal SCC, but p16 positivity outside that context should not automatically be interpreted as HPV-driven disease.

Organ preservation includes swallowing

Keeping a larynx anatomically intact is not a success if chronic aspiration or feeding dependence leaves function worse than a well-rehabilitated surgical pathway.

Dental planning precedes radiation

Teeth with poor prognosis in a high-dose field should be managed before radiotherapy when possible because extraction afterwards carries osteoradionecrosis risk.

11Common pitfallsFrequent interpretation and management errors.

01
Giving repeated antibiotics for persistent unilateral throat symptoms or an adult neck lump without direct examination and cancer referral.
02
Excising a cystic neck node before ultrasound-guided sampling, imaging and occult-primary assessment.
03
Assuming absence of tobacco exposure makes squamous cancer unlikely and overlooking HPV-related oropharyngeal disease.
04
Calling a p16-positive non-oropharyngeal tumour HPV-driven without site-appropriate confirmation.
05
Starting chemoradiotherapy without dental, nutritional, renal, hearing and swallowing preparation.
06
Using dexamethasone or nebulised treatment as definitive management of a structurally threatened airway.
07
Interrupting curative radiotherapy for preventable mucositis or dehydration without urgent supportive escalation.
08
Ending surveillance after the first reassuring response scan and missing functional late effects or second primary cancer.