Head & neck: Oropharynx — HPV/p16 prognostic significance
Free question published 22 July 2026
A 54-year-old man presents with a left tonsillar squamous cell carcinoma and an ipsilateral level II nodal mass. He has a 6 pack-year smoking history and stopped 20 years ago. p16 immunohistochemistry is strongly and diffusely positive in more than 70% of tumour cells. Staging confirms locally advanced disease suitable for definitive treatment. When counselling him about prognosis and explaining the rationale for his treatment pathway, which single statement is most accurate?
- Ap16-positive tumours carry a worse prognosis because they present at a more advanced nodal stage
- BHPV/p16-positive status is an independent favourable prognostic factor, associated with markedly better overall survival than p16-negative disease
- Cp16 status is relevant only to choice of systemic agent and has no bearing on survival
- DHis smoking history outweighs HPV status, placing him in the highest-risk prognostic group
- Ep16 positivity has no independent prognostic value once tumour and nodal stage are accounted for
Why B is correct
In the RTOG 0129 analysis (Ang et al., NEJM 2010), tumour HPV status was a strong and independent prognostic factor for survival: HPV-positive oropharyngeal cancers had a 3-year overall survival of 82.4% versus 57.1% for HPV-negative tumours, and a 58% reduction in the risk of death after adjustment for stage, tobacco exposure and treatment. NICE NG36 accordingly mandates p16 testing of all oropharyngeal squamous cell carcinomas.
And why the others are not
- AWrong — p16-positive disease carries a better, not worse, prognosis despite often presenting with more advanced nodal stage.
- CWrong — p16 status is primarily prognostic for survival; it does not change the standard systemic agent (cisplatin remains standard).
- DWrong — with only 6 pack-years and favourable stage, recursive-partitioning analysis would place him in a low-risk group, not the highest-risk group.
- EWrong — the survival advantage persisted after adjustment for age, race, tumour and nodal stage, tobacco exposure and treatment, confirming independent prognostic value.
Source RTOG 0129 (Ang et al.) — Human papillomavirus and survival of patients with oropharyngeal cancer — Ang KK, Harris J, Wheeler R, et al. N Engl J Med 2010;363(1):24-35. DOI 10.1056/NEJMoa0912217. PMID 20530316.
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