The Graham Group
Human papillomaviruses infect epithelial sites to cause benign disease (e.g. warts) but persistent infection can lead to cancer formation (e.g oropharyngeal and anogenital precancers and cancers). We are dissecting the link between the HPV life cycle and epithelial biology. Understanding this link will lead to novel therapies and uncover new prognostic markers of HPV-associated disease.
A vaccine against cancer-causing human papillomaviruses has been delivered to 12-13 year-old girls since 2008 and boys since 2019. However, the vaccine is prophylactic and cannot protect older people already infected and at risk of disease. New therapies are required to treat individuals with HPV-associated disease, both benign and tumourigenic. In addition, we need to be able to identify individuals at risk of serious disease due to persistent infection versus those with infections that will regress (transient infection) in order to focus treatment in the clinic.
How does human papillomavirus regulate the innate immune response in keratinocytes, sentinel cells of the immune system?
Human papillomavirus infection causes a massive change in the keratinocyte transcriptome. We are mining these changes to identify novel biomarkers of transient versus persistent HPV infection.
A medical device that emits microwaves shows significant promise in treating HPV-associated lesions. We are discovering the mechanism behind this effect using in vitro 3D culture models of HPV-associated disease. We are also testing the device in vivo in animals and human subjects.
Key findings of our research so far:
- Human papillomavirus represses the keratinocyte sentinel immune response and compromises the epithelial barrier.
- A biomarker matrix of cellular and viral proteins can risk stratify HPV-associated cervical disease.
- RNA biomarkers of cervical disease show promise in risk stratifying cervical disease.
- Viral load is a positive predictor of survival in HPV-associated oropharyngeal and anal cancers.
- Microwaving reverses the tumour phenotype by interfering with HPV gene expression.
Grants and Collaborators
- Dr Campbell Roxburgh ICS
- Prof Hing Leung ICS
- Dr Kate Cuschieri (NHS Lothian)
- Prof John Doorbar (University of Cambridge)
- Dr Kim Kavanagh (University of Strathclyde)
- Dr David Millan (NHS Greater Glasgow and Clyde)
- Dr Sarah Bell (NHS Greater Glasgow and Clyde)
- Dr Matt Kidd (Emblation Limited, Alloa)
- Dr Sally Roberts (University of Birmingham)