Vulvar Cancer
Vulvar cancer is uncommon and follows two broad aetiological routes: HPV-associated disease and disease arising on a background of lichen sclerosus and differentiated intraepithelial neoplasia.
Disease categories
Major disease categories
- Vulvar squamous cell carcinoma
- Vulvar melanoma
- Extramammary Paget disease of the vulva
Molecular
Molecular considerations
HPV status and p53 status distinguish the two principal pathways. Vulvar melanoma follows melanoma biology rather than squamous biology.
Markers commonly discussed in vulvar cancer
- HPV / p16
- p53
- 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 disease, and is histology-directed.
Germline
Germline considerations
Considered where the clinical picture suggests it.
Molecular monitoring
ctDNA and liquid biopsy considerations
Investigational.
Single-cell & computation
Single-cell and algorithmic approaches
Single-cell analysis in gynaecological cancer is applied to clonal structure at relapse, where the question is whether resistant disease was present from the outset or emerged under treatment. Single-cell DNA sequencing can identify reversion events in a subpopulation before they are detectable in bulk. Algorithmic work includes homologous recombination deficiency scoring from sequencing data, mutational signature analysis, and molecular classification pipelines.
Decisions
Treatment decision questions
Questions worth raising with a treating team when a decision is being made:
- Has the aetiological pathway been characterised?
- Is the histology unambiguous, particularly where melanoma is a possibility?
Resistance
Resistance and recurrence questions
- Has the diagnosis been reviewed at recurrence?
Trials
Clinical trial considerations
Trials are limited; wider geographic search is often required.
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.