Penile Cancer
Penile cancer is uncommon in most of the world but carries a higher incidence in parts of South Asia, South America and Africa. HPV status divides it into two groups with somewhat different behaviour.
Disease categories
Major disease categories
- Penile squamous cell carcinoma
- HPV-associated subtypes
- Non-HPV-associated subtypes
- Penile melanoma
Molecular
Molecular considerations
HPV status divides the disease. TP53 and CDKN2A alterations are described in HPV-independent tumours. PD-L1 expression is assessed in advanced disease.
Markers commonly discussed in penile cancer
- HPV / p16
- TP53
- CDKN2A
- PD-L1
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
Profiling is discussed in advanced and recurrent disease.
Germline
Germline considerations
Not routinely indicated.
Molecular monitoring
ctDNA and liquid biopsy considerations
Investigational.
Single-cell & computation
Single-cell and algorithmic approaches
Single-cell sequencing in genitourinary cancer is used to characterise lineage plasticity — particularly the transition towards neuroendocrine phenotype, which is a cell-state change that bulk profiling can miss entirely. Single-cell DNA analysis addresses clonal structure across metastatic sites, which is frequently discordant. Algorithm work includes DNA damage repair pathway scoring, resistance-alteration detection from serial plasma, and models that integrate imaging and molecular trajectories.
Decisions
Treatment decision questions
Questions worth raising with a treating team when a decision is being made:
- Has HPV status been assessed?
- Is the extent of inguinal nodal disease documented?
- Has management at a centre with experience of this disease been considered?
Resistance
Resistance and recurrence questions
- Has the disease been re-characterised at recurrence?
Trials
Clinical trial considerations
Trials are limited and concentrated at specialist centres.
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.