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Cancers of the mouth and throat, increasingly caused by HPV. Immunotherapy is first line for advanced disease and now used before surgery.
Head and neck squamous cell carcinoma arises from the lining of the mouth, throat (oropharynx, hypopharynx), voice box, and nose, and includes the distinct Epstein-Barr-virus-driven nasopharyngeal carcinoma. Two epidemics coexist: tobacco- and alcohol-related cancers, declining in rich countries but common globally, and HPV-driven oropharyngeal cancer, rising among younger non-smokers and now the most common HPV cancer in the US. HPV-positive disease is far more curable (3-year survival >80%) and has its own staging system.
Curative treatment is surgery (increasingly transoral robotic surgery) and/or cisplatin-based chemoradiation with IMRT; both leave lasting effects on speech, swallowing, and salivation, which is why de-escalation for HPV-positive disease has been pursued so hard, and why its repeated failure (RTOG 1016, De-ESCALaTE, NRG-HN005) matters. Immunotherapy transformed recurrent and metastatic disease: nivolumab (CheckMate 141) and then pembrolizumab first line (KEYNOTE-048) replaced the cetuximab-chemotherapy EXTREME regimen, and in June 2025 KEYNOTE-689 delivered the first perioperative approval, doubling event-free survival by giving pembrolizumab before and after surgery. Immunotherapy given concurrently with chemoradiation, by contrast, has failed repeatedly. Nasopharyngeal carcinoma gained its first US approval with toripalimab plus chemotherapy in 2023.
What is coming: EGFR-directed bispecifics with pembrolizumab (petosemtamab, ficerafusp alfa) posting response rates two to three times those of pembrolizumab alone in early trials, now in phase 3; photoimmunotherapy (approved in Japan) in global phase 3; ctHPV-DNA to guide response-adapted de-escalation; and B7-H3 and EGFR×HER3 ADCs. Open problems include the lack of targets beyond EGFR and PD-1, the functional toxicity of curative treatment, and the lower cure rate of HPV-negative disease.
Averages across everyone diagnosed, often years ago. A median is the middle of a group: half the people counted lived longer than the figure shown, and some lived far longer. Your stage, subtype, age, fitness and the treatment you receive matter more than the average, and the numbers are improving quickly.
~900,000 cases per year; HPV-driven oropharyngeal cancer rising, tobacco-related declining.
Site decides cause and behaviour: HPV drives oropharyngeal cancer, EBV drives nasopharyngeal cancer, tobacco drives oral and laryngeal cancer; all drain into the neck node levels that surgeons and radiotherapists map.
Same organ: Acinic cell carcinoma of the salivary glands, Carcinoma ex pleomorphic adenoma, Multiple endocrine neoplasia type 1 (MEN1), Multiple endocrine neoplasia type 2 (MEN2A and MEN2B), Hyperparathyroidism-jaw tumour syndrome (CDC73-related parathyroid carcinoma), Oropharyngeal cancer (tonsil and base of tongue), Laryngeal and hypopharyngeal cancer, Oral cavity cancer (mouth and tongue), Nasopharyngeal carcinoma, Salivary gland cancers, Papillary thyroid cancer, Follicular thyroid cancer, Medullary thyroid cancer, Anaplastic thyroid cancer, Thyroid cancer, Nasal cavity and paranasal sinus cancers (including esthesioneuroblastoma), NUT carcinoma (midline carcinoma with NUTM1 rearrangement), Parathyroid carcinoma, Multiple endocrine neoplasia syndromes (MEN1, MEN2, MEN4), HPV-positive oropharyngeal cancer, HPV-negative head and neck squamous cell carcinoma (including HPV-negative oropharyngeal cancer), Recurrent or metastatic head and neck squamous cell carcinoma, Hypopharyngeal cancer, Adenoid cystic carcinoma, Salivary duct carcinoma, Mucoepidermoid carcinoma, Oral tongue and floor of mouth cancer, Buccal mucosa and gingivobuccal cancer (oral cancer in India), Lip cancer, Locoregionally advanced nasopharyngeal carcinoma (stage III to IVA), Recurrent and metastatic nasopharyngeal carcinoma, Esthesioneuroblastoma (olfactory neuroblastoma), Sinonasal undifferentiated carcinoma (SNUC) and SWI/SNF-deficient sinonasal carcinoma
Most people reading this do not have advanced disease. The map describes what can happen over the whole course of the illness, across autopsy and registry series; today's staging scans find spread earlier, and each site has treatments, from focused radiotherapy for a few spots to drugs that reach the brain.
What helpsPembrolizumab with or without chemotherapy first line; neck dissection or radiotherapy clears nodes; EGFR-directed bispecifics with PD-1 blockade are in phase 3.
Also on OnCo: Atlas of advanced disease · How cancer spreads: the metastasis stages.
Neck node status is the main prognostic factor and decides neck dissection or radiotherapy.
The commonest distant site; also where second primary cancers from smoking appear.
Also on OnCo: Symptoms and red flags · Early detection roadmap.
Neoadjuvant + adjuvant pembrolizumab with surgery; or chemoradiation.
Pembrolizumab ± platinum/5-FU; cetuximab-based; photoimmunotherapy (Japan).
HPV vaccination (also prevents oropharyngeal cancer in men), tobacco and alcohol cessation; no validated screening.
Single-modality surgery or radiation; sentinel node or elective neck dissection for oral cavity; larynx preservation with radiation for T1-T2 glottic cancer.
TORS with pathology-guided adjuvant therapy or definitive (chemo)radiation; standard 70 Gy dose because de-escalation trials failed.
Neoadjuvant pembrolizumab, surgery, adjuvant pembrolizumab with (chemo)radiation for PD-L1 CPS ≥1 (KEYNOTE-689); otherwise surgery then risk-adapted (chemo)radiation.
Cisplatin (100 mg/m² q3w or weekly) with 70 Gy IMRT; cetuximab-radiation only if cisplatin-ineligible; concurrent immunotherapy is not indicated (JAVELIN Head and Neck 100, KEYNOTE-412) and adding xevinapant to chemoradiation gave no benefit (TrilynX).
Pembrolizumab alone (CPS ≥20, or ≥1) or with platinum/5-FU (any CPS); EXTREME if immunotherapy contraindicated.
Nivolumab or pembrolizumab if immunotherapy-naive; otherwise cetuximab, taxane, or methotrexate; clinical trials (bispecifics, ADCs).
Cetuximab sarotalocan photoimmunotherapy; re-irradiation (proton or IMRT) in selected patients elsewhere.
Induction gemcitabine-cisplatin then chemoradiation for locoregional disease; toripalimab (or other PD-1) + gemcitabine-cisplatin for recurrent/metastatic; plasma EBV DNA for surveillance.
Swallowing and speech therapy, dental care after radiation, thyroid monitoring, lymphoedema management, smoking cessation; second primary surveillance.
Trials recruiting now, the landmark trials, the trials held by this cancer's subtypes, the key papers and what they mean, the latest literature, and the milestones year by year.
Cases by country, the UK and NHS pathway and other country lenses, the expert centres with trials on record, and the centres named on this cancer's subtypes.
One section per setting: the options named, what each is for, the trials behind them, the recorded trade-offs and the questions to ask.
Persistent headache with extreme tiredness, nausea, dizziness on standing or low blood pressure. Vomiting, severe weakness or collapse is adrenal crisis.
No pharmacokinetic interactions expected (antibody). See the irAE guide for toxicity management.
Immunotherapy can attack hormone-producing glands: most often the thyroid (usually ending in an under-active thyroid needing lifelong tablets), and less often the pituitary (hypophysitis) or adrenal glands, which can be life-threatening if missed.
Immune-related adverse events (irAEs) are the autoimmune side effects of checkpoint inhibitors: colitis, thyroid problems, rash, hepatitis, pneumonitis.
See all on the product pages:NivolumabPembrolizumabToripalimab·Printable cards in the navigator
Newly diagnosed? Read the first 60 days with Head and neck squamous cell carcinoma, then print the one-page appointment sheet with room for the answers.
Print this page for your appointment (your browser's print command). These prompts are for discussion; your clinical team knows your case.
Everything in development, the medicines held by this cancer's subtypes, the open problems and what is being done about them, the roadmaps, and what changed on this record.
Every connected record, the notes, the JSON, Markdown and RDF twins, and where the record came from and when it was checked.