Loading
10 slides generated from the cancer page, with a quiz from the open benchmark and speaker notes that cite the sources. Arrow keys move between slides; Print gives one slide per page.
Head and neck cancers caused by tobacco and alcohol rather than HPV are harder to cure: surgery or cisplatin chemoradiation is the mainstay, immunotherapy given around surgery (KEYNOTE-689) or after it (NIVOPOSTOP) has begun to help, and pembrolizumab is the first treatment once the disease has spread.
HPV-negative head and neck squamous cell carcinoma is the classical, tobacco and alcohol driven disease of the oral cavity, larynx, hypopharynx and oropharynx, with areca nut and chewed tobacco the cause in South Asia. Tumours almost always carry TP53 mutation and CDKN2A loss, often EGFR overexpression, and arise from a field of damaged mucosa that produces second primaries; HPV-negative oropharyngeal cancer had three-year survival of 57.1 percent in the RTOG 0129 analysis against 82.4 percent for HPV-positive disease, and it is staged and treated with the other HPV-negative sites rather than with HPV-positive oropharyngeal cancer.
Curative treatment is surgery followed by radiotherapy, with cisplatin added when there is extranodal extension or a positive margin (the Bernier and Cooper trials of 2004), or definitive cisplatin chemoradiation, which the MACH-NC meta-analysis showed adds about 6.5 percentage points to five-year survival over radiotherapy alone; cetuximab with radiotherapy (Bonner) is the option for patients who cannot have cisplatin. Adding PD-1 or PD-L1 antibodies during chemoradiation failed in JAVELIN Head and Neck 100 and KEYNOTE-412, and the radiosensitiser xevinapant made outcomes worse in TrilynX, but immunotherapy around surgery has succeeded: KEYNOTE-689 gave median event-free survival of 59.7 against 29.6 months with perioperative pembrolizumab in tumours with a PD-L1 combined positive score of 1 or more, and NIVOPOSTOP raised three-year disease-free survival from 52.5 to 63.1 percent with nivolumab added to postoperative chemoradiation.
| Setting | Approach | Guideline |
|---|---|---|
| Diagnosis and staging | Biopsy with p16 (and HPV testing for oropharyngeal primaries), PD-L1 combined positive score, panendoscopy for second primaries, CT or MRI and PET-CT for stage III to IV. | not mapped |
| Resectable stage III to IVA | Surgery with neck dissection; perioperative pembrolizumab for tumours with a combined positive score of 1 or more (KEYNOTE-689), then radiotherapy or chemoradiation by pathology. | NCCN Category 1 |
| After surgery, high risk | Postoperative cisplatin chemoradiation for extranodal extension or positive margins; nivolumab added on the basis of NIVOPOSTOP. | NCCN Category 1 (chemoradiation) |
| Unresectable or organ-preserving | Definitive cisplatin chemoradiation to 70 Gy; cetuximab with radiotherapy for patients who cannot have cisplatin (Bonner). | NCCN Category 1 |
| Recurrent or metastatic | Pembrolizumab alone (combined positive score 1 or more) or with platinum-fluorouracil (KEYNOTE-048); cetuximab-based EXTREME for rapid disease or PD-1 failure. | NCCN Category 1 |
| Resource-limited settings | Oral metronomic methotrexate with celecoxib, with or without low-dose nivolumab (Tata Memorial trials). | not mapped |
| Prevention | Smoking cessation, alcohol reduction and betel quid cessation; second primaries make cessation after diagnosis worthwhile. | not mapped |