Vaginal Cancer
Primary vaginal cancer is rare. Most malignancy found in the vagina is secondary spread from another site, so establishing that a tumour is genuinely a vaginal primary is the first question.
Disease categories
Major disease categories
- Vaginal squamous cell carcinoma
- Vaginal adenocarcinoma
- Vaginal melanoma
- Vaginal sarcoma
Molecular
Molecular considerations
HPV association is present in most squamous vaginal cancers. PIK3CA alterations are described. Vaginal melanoma follows melanoma biology and is assessed accordingly.
Markers commonly discussed in vaginal cancer
- HPV / p16
- PD-L1
- PIK3CA
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 directed by histology.
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 a primary elsewhere been excluded?
- Has HPV status been assessed?
- Is the histology confirmed, 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 and basket-trial 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.