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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.
Throat cancers caused by HPV are usually cured with chemoradiation or robotic surgery, so trials now ask how much treatment can be taken away: swapping cisplatin for cetuximab failed, cutting the radiation dose has worked only after surgery so far, and blood tests for HPV DNA may pick out the patients who can safely have less.
HPV-positive oropharyngeal squamous cell carcinoma arises in the tonsils and base of tongue when high-risk human papillomavirus, almost always type 16, integrates into the crypt epithelium and its E6 and E7 proteins disable p53 and Rb. Tumours are recognised by strong p16 staining, confirmed by HPV DNA or RNA testing where available, and they present with a neck node and a small primary. The RTOG 0129 analysis by Ang and colleagues in 2010 showed three-year overall survival of 82.4 percent for HPV-positive against 57.1 percent for HPV-negative disease, with smoking history worsening the outlook, and the eighth edition of the staging system gave HPV-positive disease a staging system of its own.
Standard treatment is cisplatin chemoradiation to 70 Gy, or transoral robotic surgery with neck dissection followed by pathology-guided adjuvant treatment for smaller tumours. Two trials that replaced cisplatin with cetuximab to spare toxicity both failed: RTOG 1016 found five-year overall survival of 84.6 percent with cisplatin against 77.9 percent with cetuximab, and De-ESCALaTE found two-year survival of 97.5 against 89.4 percent, so cetuximab is reserved for patients who cannot have cisplatin. The Canadian ORATOR trial found swallowing scores slightly better after radiotherapy than after surgery, so neither route is superior for every patient.
| Setting | Approach | Guideline |
|---|---|---|
| Diagnosis and staging | Fine-needle biopsy of the neck node with p16 staining, HPV confirmation where p16 is equivocal, examination and imaging of the tonsils and tongue base, and PET-CT; staged with the HPV-positive system. | not mapped |
| Early disease (small primary, limited nodes) | Transoral robotic surgery with neck dissection and pathology-guided adjuvant radiotherapy (E3311), or radiotherapy alone; choice by expected swallowing and voice. | NCCN Category 2A |
| Locally advanced disease | Cisplatin chemoradiation to 70 Gy; cetuximab only for patients who cannot have cisplatin, since RTOG 1016 and De-ESCALaTE showed it inferior. | NCCN Category 1 |
| De-escalation | Reduced-dose or chemotherapy-free treatment only within a trial; NRG-HN005 showed that lowering the dose in definitive chemoradiation on HPV status alone loses control. | not mapped |
| Surveillance | Examination and PET-CT at about three months; circulating tumour HPV DNA is emerging as a blood test for recurrence. | not mapped |
| Recurrent or metastatic | Pembrolizumab alone or with platinum-fluorouracil (KEYNOTE-048); HPV-positive tumours respond at least as well as HPV-negative ones. | NCCN Category 1 |
| Prevention | HPV vaccination of girls and boys before exposure; catch-up vaccination of men is being argued for. | not mapped |