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Human Papilloma Virus infects epithelial cells, driving tumourigenesis primarily from incorporation of DNA into the host cellular genome. Translation of two particular Human Papilloma Virus\u2013specific oncoproteins, E6 and E7, are the key drivers of malignancy. If diagnosed early cervical, vaginal and vulval cancers have good prognosis and are treated with curative intent. However, metastatic disease carries a poor prognosis, with first-line systemic treatment providing only modest increase in outcome. Having shown promise in other solid malignancies, immune checkpoint inhibition and therapeutic cancer vaccines have been directed towards Human Papilloma Virus\u2013associated gynaecological cancers, mindful that persistent Human Papilloma Virus infection drives malignancy and is associated with immunosuppression and lack of T-cell immunity. In this review, we discuss novel therapeutic approaches for targeting Human Papilloma Virus\u2013driven gynaecological malignancies including vaccination strategies, use of immunomodulation, immune checkpoint inhibitors and agents targeting Human Papilloma Virus\u2013specific oncoproteins. We also highlight the evolving focus on exciting new treatments including adoptive T-cell therapies.<\/jats:p>","DOI":"10.1177\/1745506520961709","type":"journal-article","created":{"date-parts":[[2020,12,10]],"date-time":"2020-12-10T13:50:12Z","timestamp":1607608212000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":5,"title":["Targeting HPV in gynaecological cancers \u2013 Current status, ongoing challenges and future directions"],"prefix":"10.1177","volume":"16","author":[{"given":"Shanthini M","family":"Crusz","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, St Bartholomew\u2019s Hospital, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karim","family":"El-Shakankery","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, St Bartholomew\u2019s Hospital, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rowan E","family":"Miller","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, St Bartholomew\u2019s Hospital, London, UK"},{"name":"Department of Medical Oncology, University College London Hospital, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2020,12,9]]},"reference":[{"key":"bibr1-1745506520961709","unstructured":"National Cancer Institute at the National Institutes of Health. 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