Head & Neck Cancer
Head and neck cancer covers several anatomical subsites whose biology differs. Human papillomavirus status in oropharyngeal cancer, in particular, identifies a group with distinct biology and a distinct natural history.
Disease categories
Major disease categories
- Oropharyngeal cancer
- Oral cavity cancer
- Laryngeal cancer
- Hypopharyngeal cancer
- Nasopharyngeal carcinoma
- Salivary gland tumours
Molecular
Molecular considerations
HPV status, assessed via p16 immunohistochemistry and HPV testing, is central in oropharyngeal cancer. TP53, CDKN2A, PIK3CA and NOTCH1 alterations are frequently described. PD-L1 expression is commonly assessed in recurrent and metastatic disease. Epstein–Barr virus association is relevant in nasopharyngeal carcinoma.
Markers commonly discussed in head & neck cancer
- p16 / HPV status
- EBV (nasopharyngeal)
- PD-L1
- TP53
- PIK3CA
- CDKN2A
- NOTCH1
- HRAS
Not exhaustive, and not every marker is assessed in every patient. Which of these is relevant depends on the individual case and should be discussed with the treating team.
Testing
Genomic testing considerations
HPV and p16 assessment at the relevant subsites, PD-L1 in recurrent or metastatic disease, and broader panels where a targeted option is being considered.
Germline
Germline considerations
Germline assessment is considered where age, family history or a syndromic feature suggests it. Fanconi anaemia is relevant in a small number of young patients.
Molecular monitoring
ctDNA and liquid biopsy considerations
HPV circulating tumour DNA is an area of substantial research interest in oropharyngeal cancer, particularly for surveillance.
Single-cell & computation
Single-cell and algorithmic approaches
Single-cell sequencing in head and neck cancer is used to characterise immune exclusion and the stromal compartment, both of which vary substantially between tumours that look similar histologically. Single-cell DNA analysis contributes to field-change questions — whether a second lesion is a recurrence or an independent primary, which clonal analysis can often settle. Algorithm work includes HPV integration site analysis, deconvolution of immune composition from bulk expression, and viral circulating-DNA trajectory modelling.
In practice
What a review of this disease typically surfaces
Subsite is the recurring gap. 'Head and neck cancer' in a referral covers regions with quite different biology, and p16 or HPV status is only interpretable once the subsite is known — p16 carries a different meaning in the oropharynx than outside it. Cases also arrive where a new lesion has been assumed to be recurrence when a second primary is at least as likely, given the field change that underlies much of this disease.
Patterns observed across precision oncology case reviews. Every case differs; these are the questions worth checking, not conclusions about any individual patient.
Decisions
Treatment decision questions
Questions worth raising with a treating team when a decision is being made:
- Has HPV or p16 status been established at the relevant subsite?
- Is the anatomical subsite recorded precisely?
- Has PD-L1 been assessed where relevant?
Resistance
Resistance and recurrence questions
- Has the disease been re-characterised at recurrence?
- Is a second primary being considered rather than recurrence?
Trials
Clinical trial considerations
HPV status, subsite and prior treatment all affect plausible trial eligibility.
When a precision oncology review may help
A review is most useful where the standard pathway has been exhausted or where the picture is more complicated than a protocol accounts for — rare presentations, treatment resistance, complex or apparently contradictory molecular findings, or a decision between several defensible options.
The output is a structured analysis and a set of questions for the treating team. It is not treatment, and it does not replace the treating oncologist.