{"entity":{"id":"hypopharyngeal-cancer","kind":"cancer","name":"Hypopharyngeal cancer","aka":["Hypopharynx cancer","Pyriform sinus cancer","Piriform fossa cancer","Postcricoid cancer"],"tldr":"Cancer of the hypopharynx, the funnel behind the voice box, is the head and neck cancer with the worst outlook because it grows silently and spreads to the neck early. Treatment is chemoradiation to keep the larynx where possible, or removal of the larynx and pharynx with reconstruction for the most extensive tumours.","summary":"Hypopharyngeal squamous cell carcinoma arises in the pyriform sinuses, the posterior pharyngeal wall or the postcricoid region, the mucosa-lined funnel between the oropharynx and the oesophagus that wraps around the back of the larynx. It causes few symptoms until it is large: a sore throat, pain referred to the ear, difficulty swallowing and, most often, a lump in the neck, so most patients present with stage III or IV disease, and many are malnourished. Tobacco and alcohol are the causes, and a second primary in the oesophagus or lung is common enough that panendoscopy is part of staging.\n\nThe landmark trial is EORTC 24891, reported by Lefebvre in 1996, which compared induction cisplatin and fluorouracil followed by radiotherapy in responders with total laryngectomy and partial pharyngectomy followed by radiotherapy: survival was no different and a proportion of survivors in the chemotherapy arm kept a working larynx, establishing larynx preservation as a legitimate aim. Concurrent cisplatin chemoradiation, shown in RTOG 91-11 to preserve the larynx best in laryngeal cancer, became the usual organ-preserving approach for hypopharyngeal cancer too, with cetuximab and radiotherapy (Bonner, which included hypopharyngeal tumours) for patients who cannot have cisplatin.\n\nTumours that have destroyed the laryngeal cartilage, fixed the vocal cords or extended into the cervical oesophagus, and those that recur after chemoradiation, are treated by laryngopharyngectomy, reconstructed with a free jejunal, anterolateral thigh or radial forearm flap, or a gastric pull-up when the oesophagus is involved, followed by postoperative radiotherapy or chemoradiation for extranodal extension or positive margins. Recurrent or metastatic disease is treated as for other head and neck squamous cell carcinoma with pembrolizumab-based therapy. Smoking cessation, nutritional support and swallowing rehabilitation are part of every plan.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Hypopharyngeal_cancer","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Hypopharyngeal_cancer"}],"tags":["subtype-page","head-and-neck"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-bonner-cetuximab-radiotherapy-nejm-2006","paper-eortc-24891-larynx-preservation-lefebvre-jnci-1996"],"journals":[],"dependsOn":[],"notes":[],"group":"head and neck","burden":"About 84,000 new cases a year worldwide, overwhelmingly in men who smoke and drink heavily; it presents late, spreads to the neck early and has among the lowest survival of any head and neck site.","subtypes":["Pyriform (piriform) sinus cancer, the commonest hypopharyngeal site","Posterior pharyngeal wall cancer","Postcricoid cancer (historically linked to iron-deficiency Plummer-Vinson syndrome in women)","Hypopharyngeal cancer extending to the larynx or cervical oesophagus"],"biomarkers":["Stage, cartilage invasion and oesophageal extension on CT or MRI","Vocal cord fixation","Second primary in the oesophagus or lung at panendoscopy","Nutritional status","PD-L1 combined positive score (recurrent disease)"],"standardOfCare":[{"setting":"Diagnosis and staging","approach":"Panendoscopy with biopsy, CT of the neck and chest, PET-CT for stage III to IV, and assessment of swallowing and nutrition before treatment.","refs":["pet-ct"],"guideline":{"version":"NCCN Guidelines: Head and Neck Cancers","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1437"}},{"setting":"Early disease (T1 to T2, node-negative)","approach":"Radiotherapy alone, or transoral or open partial pharyngectomy in selected small tumours, with treatment of both sides of the neck.","refs":["imrt-igrt","tors"],"guideline":{"nccn":"Category 2A","version":"NCCN Guidelines: Head and Neck Cancers","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1437"}},{"setting":"Locally advanced, larynx preservable","approach":"Concurrent cisplatin chemoradiation to 70 Gy; induction cisplatin-fluorouracil (EORTC 24891) or docetaxel-cisplatin-fluorouracil followed by radiotherapy in some centres.","refs":["cisplatin","fluorouracil","docetaxel","chemoradiation","imrt-igrt","rtog-91-11"],"guideline":{"nccn":"Category 1 (concurrent chemoradiation)","version":"NCCN Guidelines: Head and Neck Cancers","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1437"}},{"setting":"Cannot have cisplatin","approach":"Cetuximab with radiotherapy (Bonner), or carboplatin-based chemoradiation.","refs":["cetuximab","bonner-cetuximab-rt","carboplatin"],"guideline":{"nccn":"Category 2A","version":"NCCN Guidelines: Head and Neck Cancers","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1437"}},{"setting":"Extensive disease (cartilage destruction, oesophageal extension) or recurrence after radiotherapy","approach":"Total laryngopharyngectomy with neck dissection and free-flap or gastric pull-up reconstruction, then postoperative radiotherapy or cisplatin chemoradiation by pathology.","refs":["imrt-igrt","cisplatin","chemoradiation"],"guideline":{"nccn":"Category 2A","version":"NCCN Guidelines: Head and Neck Cancers","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1437"}},{"setting":"Recurrent or metastatic","approach":"Pembrolizumab alone or with platinum-fluorouracil (KEYNOTE-048).","refs":["pembrolizumab","keynote-048","recurrent-metastatic-hnscc"],"guideline":{"nccn":"Category 1","version":"NCCN Guidelines: Head and Neck Cancers","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1437"}},{"setting":"Prevention","approach":"Smoking cessation and alcohol reduction; no screening programme exists.","refs":["smoking-cessation-after-diagnosis","alcohol-reduction-labelling"]}],"stateOfArt":["Organ preservation with chemoradiation is standard for most locally advanced tumours, but survival is poorer than for laryngeal cancer at the same stage.","Free-flap reconstruction has made laryngopharyngectomy safer and restored swallowing for many.","Immunotherapy around surgery (KEYNOTE-689, NIVOPOSTOP) applies to hypopharyngeal cancer, which was well represented in both trials."],"history":[{"year":1996,"title":"EORTC 24891: induction chemotherapy and radiotherapy preserve the larynx without loss of survival","refs":[]},{"year":2003,"title":"RTOG 91-11: concurrent cisplatin chemoradiation preserves the larynx best","refs":["rtog-91-11"]},{"year":2006,"title":"Cetuximab with radiotherapy (Bonner) includes hypopharyngeal tumours","refs":["bonner-cetuximab-rt"]},{"year":2019,"title":"KEYNOTE-048: pembrolizumab first line in recurrent disease","refs":["keynote-048"]},{"year":2025,"title":"NIVOPOSTOP: nivolumab after surgery for high-risk disease","refs":["nivopostop"]}],"pipeline":["nivopostop","keynote-689","adaptive-radiotherapy","pembrolizumab"],"openProblems":["Survival has barely improved in thirty years.","Choosing between preservation and laryngopharyngectomy in the most extensive tumours.","Swallowing, stricture and aspiration after chemoradiation.","Late presentation in the heavy smokers and drinkers who get the disease."],"parent":"laryngeal-cancer"},"route":"/cancers/hypopharyngeal-cancer/","neighbours":{"paper":[{"id":"paper-eortc-24891-larynx-preservation-lefebvre-jnci-1996","kind":"paper","name":"EORTC 24891: larynx preservation with induction chemotherapy in pyriform sinus (hypopharyngeal) cancer","route":"/key-papers/paper-eortc-24891-larynx-preservation-lefebvre-jnci-1996/"},{"id":"paper-bonner-cetuximab-radiotherapy-nejm-2006","kind":"paper","name":"Radiotherapy plus cetuximab for locoregionally advanced squamous cell carcinoma of the head and neck","route":"/key-papers/paper-bonner-cetuximab-radiotherapy-nejm-2006/"}],"trial":[{"id":"bonner-cetuximab-rt","kind":"trial","name":"Bonner trial (cetuximab plus radiotherapy)","route":"/trials/bonner-cetuximab-rt/"},{"id":"keynote-048","kind":"trial","name":"KEYNOTE-048","route":"/trials/keynote-048/"},{"id":"keynote-689","kind":"trial","name":"KEYNOTE-689","route":"/trials/keynote-689/"},{"id":"nivopostop","kind":"trial","name":"NIVOPOSTOP (GORTEC 2018-01)","route":"/trials/nivopostop/"},{"id":"rtog-91-11","kind":"trial","name":"RTOG 91-11","route":"/trials/rtog-91-11/"}],"technology":[{"id":"adaptive-radiotherapy","kind":"technology","name":"Adaptive radiotherapy (online replanning)","route":"/technologies/adaptive-radiotherapy/"},{"id":"alcohol-reduction-labelling","kind":"technology","name":"Alcohol reduction, pricing and cancer warning labels","route":"/technologies/alcohol-reduction-labelling/"},{"id":"imrt-igrt","kind":"technology","name":"IMRT / IGRT (modern external beam)","route":"/technologies/imrt-igrt/"},{"id":"pet-ct","kind":"technology","name":"PET/CT","route":"/technologies/pet-ct/"},{"id":"smoking-cessation-after-diagnosis","kind":"technology","name":"Smoking cessation in cancer patients","route":"/technologies/smoking-cessation-after-diagnosis/"},{"id":"tors","kind":"technology","name":"Transoral robotic surgery (TORS)","route":"/technologies/tors/"}],"drug":[{"id":"carboplatin","kind":"drug","name":"Carboplatin","route":"/drugs/carboplatin/"},{"id":"cetuximab","kind":"drug","name":"Cetuximab","route":"/drugs/cetuximab/"},{"id":"cisplatin","kind":"drug","name":"Cisplatin","route":"/drugs/cisplatin/"},{"id":"docetaxel","kind":"drug","name":"Docetaxel","route":"/drugs/docetaxel/"},{"id":"fluorouracil","kind":"drug","name":"Fluorouracil (5-FU)","route":"/drugs/fluorouracil/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}],"term":[{"id":"chemoradiation","kind":"term","name":"Chemoradiation (chemoradiotherapy, CRT)","route":"/terms/chemoradiation/"}],"cancer":[{"id":"laryngeal-cancer","kind":"cancer","name":"Laryngeal and hypopharyngeal cancer","route":"/cancers/laryngeal-cancer/"},{"id":"recurrent-metastatic-hnscc","kind":"cancer","name":"Recurrent or metastatic head and neck squamous cell carcinoma","route":"/cancers/recurrent-metastatic-hnscc/"}]}}