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Immunotherapy For Vulval Cancer

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Treatment of Vulval Cancers

Below summarizes the main points for all treatments in accordance to British Gynaecological Cancer Society (BGCS) vulval cancer guidelines: An update on recommendations for practice 2023. Please read the guidelines attached for further details.

British guidelines for vulva cancersDownload

Importance of Immunotherapy

Supporting Images For Immunotherapy for Vulva

HPV-dependent vulval intraepithelial neoplasia and vulval tumours depend on the expression of the viral oncogenes E6 and E7 and are considered vital therapeutic targets, as they have major roles in degrading the tumour suppressor genes p53 and pRB, respectively, using the ubiquitin-proteasome system. E6 binds to the ubiquitin-protein ligase (E6-AP) and forms a dimer that binds to p53. P53 undergoes ubiquitination and is then targeted for recognition by the proteasome for degradation. HPV-positive cancer cells that have low levels of oxygen (hypoxia) could influence treatment strategies, as hypoxia can downregulate the oncogenes but evade senescence (ageing of the cells) (Hoppe-Seyler et al., 2018). E7 inhibits pRB binding to E2F transcription factors; this leads to activation of cellular growth, especially the expression of E2F-responsive genes like Cyclin A and E involved in cell cycle progression. Both E6 and E7 oncoproteins are involved in inducing genomic instability by targeting telomerase. Telomerase is an enzyme that maintains telomere length. This helps to increase telomere length (the ends of the chromosomes), continue replication, and induce DNA damage.
The classification of immunotherapy
An explanation on the role of each type of immunotherapy
There are different types of vaccines. Vaccines originate from the Latin word “vacca,” meaning cow, after the development of the first vaccination produced by Edward Jenner, who used the cowpox virus for immunization against smallpox in 1798. Here, what we can establish is that some vaccines are made in the laboratory, whereas others are made in vivo using recombinant proteins from genetically engineered molecules. The first type of vaccine presented here is cell-based cancer cells. These could be referred to as whole cell vaccines or dendritic cell vaccines. In whole cell vaccines, all the proteins expressed by tumour cells, called antigens, are incorporated in the whole cell vaccine. Dendritic cell vaccines, as their name suggests, are dendritic cells (a type of immune cell) added to the vaccine, as they have a functional role as antigen-presenting cells and stimulate T cells. At first, they are isolated from the individual patient and cultured in the laboratory. This is where specific antigens, DNA, or RNA are loaded and are capable of endocytosis (getting inside the cell). They are then re-introduced into the patient.

Viral-based cancer vaccines are when engineered viruses are used as vectors. Therefore, the viruses are made in the laboratory, where they isolate and manipulate fragments of the virus and the DNA. When the recombinant virus vector is re-introduced into the body, it can replicate, delivering antigens to the immune cells. Another example is Gardasil, where the capsid protein expressed using recombinant DNA techniques helps to make virus-like particles. It is commonly used to treat cervical cancer primarily but also has shown effectiveness in other types of tumours that arise in the female reproductive system.

Peptide-based vaccines focus on using tumour-associated antigens to make an immune response via T-cells rather than the whole cells from tumours. Tumour-specific antigens vary in their characteristics and quantity on tumour cells in comparison to normal cells. Peptides (short sequences of amino acids) that code for the tumour-specific antigens are used to produce synthetic or recombinant proteins. An epitope is a particular part that is recognised by immune cells.

Nucleic acid-based vaccines are vaccines in which DNA or RNA encoding the tumour antigens is presented to the immune system using different techniques.

The ultimate goal is for the T-cells to recognise the antigens on the tumour cell surface and kill the tumour cells, whether that is associated with a virus or the ability to target tumour-specific antigens by the local delivery of gene-vector inoculation to generate a tumour-specific response that can be copied/replicated/amplified to target tumour cells at distant sites.

References

American Cancer Society (2026) Anal Cancer. Available at: https://www.cancer.org/cancer/types/anal-cancer.html (Accessed: 2nd October 2026)

British Association of Dermatologists (2026) Imiquimod cream. Available at: https://www.bad.org.uk/pils/imiquimod-cream (Accessed: 30th September 2026)

Cancer Research UK (2028) Chemotherapy for vulval cancer. Available at: https://www.cancerresearchuk.org/about-cancer/vulval-cancer/treatment/chemotherapy (Accessed: 30th September 2026)

Cleveland Clinic (2026) Volumetric Modulated Arc Therapy (VMAT). Available at: https://my.clevelandclinic.org/health/treatments/17626-volumetric-modulated-arc-therapy-vmat (Accessed: 30th September 2026)

Hoppe-Seyler, K., Bossler, F., Braun, J.A., Herrmann, A.L. and Hoppe-Seyler, F. (2018). The HPV E6/E7 Oncogenes: Key Factors for Viral Carcinogenesis and Therapeutic Targets. Trends in Microbiology, [online] 26(2), pp.158–168. doi:10.1016/j.tim.2017.07.007.

Kochhar, R., Plumb, A.A., Carrington, B.M. and Saunders, M. (2012). Imaging of Anal Carcinoma. American Journal of Roentgenology, 199(3), pp.W335-W344. doi:10.2214/ajr.11.8027.

Lobna Ouldamer, Z. Chraibi, Flavie Arbion, Barillot, I. and Body, G. (2013). Bartholin’s gland carcinoma: Epidemiology and therapeutic management. 22(2), pp.117–122. doi:10.1016/j.suronc.2013.02.004.

Morrison, J., Baldwin, P., Hanna, L., Andreou, A., Buckley, L., Durrant, L., Edey, K., Faruqi, A., Fotopoulou, C., Ganesan, R., Hillaby, K. and Taylor, A. (2024). British Gynaecological Cancer Society (BGCS) vulval cancer guidelines: An update on recommendations for practice 2023. PubMed, 292, pp.210–238. Doi: 10.1016/j.ejogrb.2023.11.013.

National Cancer Institute (2026) Vulvar Cancer Treatment (PDQ®)–Health Professional Version. Available at: https://www.cancer.gov/types/vulvar/hp/vulvar-treatment-pdq (Accessed: 17th August 2026)

Royal College of Obstetricians and Gynaecologists (2014) Guidelines for the Diagnosis and Management of  Vulval Carcinoma.  Available at: https://www.rcog.org.uk/media/dqwnw2a1/vulvalcancerguideline.pdf (Accessed: 1st October 2026)

The Eve Appeal (2026) Vulval cancer Available at; https://eveappeal.org.uk/information-and-advice/gynaecological-cancers/vulval-cancer/  (Accessed: 7th August 2026)

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