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HPV-related oropharyngeal cancer
HPV-related oropharyngeal cancer (mainly HPV-16, p16-positive) appears in younger patients, sometimes non-smokers, often as a cystic neck node with a small tumour in the tonsil or tongue base; its prognosis is much better, so it has a separate staging system.
Why it matters in the exam
The exam asks about the differences between HPV-related and non-HPV disease: with HPV — younger age, less smoking, a link to sexual behaviour, a cystic neck mass, and a small primary in the palatine or lingual tonsil; the marker is immunohistochemical staining for p16. Smoking of more than 10 pack-years worsens the prognosis even in an HPV-positive tumour. Under AJCC 8 for a p16-positive tumour: T1 — up to 2 cm; T2 — 2 to 4 cm; T3 — over 4 cm or extension to the lingual surface of the epiglottis; clinical N1 — ipsilateral nodes up to 6 cm; N2 — contralateral or bilateral nodes up to 6 cm; N3 — over 6 cm.
Treatment: radiotherapy with concurrent cisplatin, or transoral robotic surgery (TORS) with neck dissection, followed by adjuvant therapy according to the findings. Attempts to de-escalate by replacing cisplatin with cetuximab failed — cetuximab was less effective (RTOG 1016 and De-ESCALaTE). Cetuximab is a monoclonal antibody against the epidermal growth factor receptor (EGFR). A p16-negative tumour behaves like "classic" squamous cancer and is staged with the usual system.
In head and neck squamous cell carcinoma that has recurred or metastasised, pembrolizumab and nivolumab are antibodies against PD-1 (immune checkpoint inhibitors). Under KEYNOTE-048, pembrolizumab (alone or with chemotherapy) is first line when the CPS is 1 or more; nivolumab improved survival after platinum failure (CheckMate 141). HPV vaccination is the means of primary prevention, and there is currently no recommended screening test for oropharyngeal cancer.
Key points
- HPV-16 and p16 as the marker.
- Young, cystic node, good prognosis.
- Separate staging in AJCC 8.
- Cisplatin is better than cetuximab.
- Recurrent disease: PD-1 inhibitors.
Summary table
| Aspect | HPV-related (p16+) | Not HPV-related |
|---|---|---|
| Who | Younger, sometimes a non-smoker | Smoker and drinker |
| Presentation | Cystic neck node, small primary | Locally advanced tumour |
| Prognosis | Much better | Worse |
| Staging | Separate system in AJCC 8 | Usual system |
| Treatment | Radiotherapy with cisplatin or TORS with dissection | Radiotherapy with cisplatin or surgery |
Free exam questions
מה המאפיין של חולים בסרטן לוע ( Oropharyngeal Cancer ) שנגרם על ידי נגיף הפפילומה ( HPV )? (the question as examined, in Hebrew)
- א. עישון וצריכת אלכוהול
- ב. גיל מעל 60
- ג. פרוגנוזה טובה
- ד. KERATINIZING SCC
איזה מהבאים לא מהווה מדד פרוגנוסטי ב-Squamous Cell Carcinoma של הלרינקס? (the question as examined, in Hebrew)
- א. נוכחות DNA HPV בגידול
- ב. Histologic grade
- ג. Pattern of invasion
- ד. נוכחות בלוטות מעורבות בצוואר
מהו מנגנון הפעולה של התרופות PEMBROLIZUMAB ו - NIVOLUMAB ? (the question as examined, in Hebrew)
- א. חסימת הקולטן EGFR
- ב. הגברת רגישות הגידול לקרינה
- ג. עיכוב יצירת כלי דם( anti angiogenic )
- ד. חסימת הקולטן PD-1
In the full version for subscribers
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Sources
- AJCC Cancer Staging Manual, 8th edition (2017) — HPV-mediated (p16+) oropharyngeal cancer
- NCCN Clinical Practice Guidelines in Oncology: Head and Neck Cancers — Cancer of the Oropharynx, 2025 — Treatment and systemic therapy
- Burtness B et al. KEYNOTE-048 (Lancet), 2019 — Pembrolizumab in recurrent or metastatic head and neck SCC
Sources are given for further reading; the text is written afresh and not copied from them.
Reviewed by the Examqo AI Professor · 2026-11-06. The text may contain errors; when in doubt, check the source.