New research brings hope to head and neck cancer survivors with radiotherapy-induced dry mouth

A UCLH patient has received an innovative treatment for radiotherapy-induced dry mouth, an irreversible serious adverse effect of head and neck cancer radiotherapy that causes permanent impairment of talking and eating.

Researchers hope that the gene therapy, called AAV2-hAQP1, will significantly improve the lives of patients who survived oral and oropharyngeal cancer but developed persistent dry mouth (known as xerostomia) from irreversible radiation damage to the salivary glands.

The international (US, Canada and UK) study AQUAx2, which is sponsored by MeiraGTx, is a gene transfer study. It is the first in the UK to attempt to increase the amount of saliva and reduce the associated dry mouth symptoms via transferring the Aquaporin 1 (hAQP1) gene to the salivary glands disrupted by the anti-cancer radiotherapy.

The study uses a viral vector (a modified virus) to deliver a gene designed to make a specific protein, called Aquaporin, that acts as a ‘water channel’: it forms pores in the cells to facilitate the transport of water. The residual salivary gland cells become more permeable to water and allow water to flow down into the mouth to moisten it. The therapy is designed to be given just once.

The UCLH study PI is Stefano Fedele, Professor/Honorary Consultant of Oral Medicine and Lead of the NIHR UCLH Biomedical Research Centre Oral and Dental Medicine Theme.

Prof Fedele said: "Xerostomia (dry mouth) is a condition in which a person’s salivary glands do not produce enough saliva. Up to 90% of head and neck cancer patients treated with radiotherapy develop permanent damage to the salivary glands and the associated symptoms including difficulty eating, chewing, and speaking, altered taste, oral pain, and difficulty sleeping. They also incur recurrent fungal infections and hard-to-treat dental caries (tooth decay), which causes further suffering and disruption of their day-to-day activities."

Head and neck cancers are the sixth most common cancer group globally and eight most common in the UK. Incidence rates are increasing in England, largely driven by oropharyngeal cancer (47% increase since 2013), with over 11,000 new cases recorded in 2021. The mortality rate for head and neck cancer has continued to increase, while most other cancer mortality rates fell.

Current data also show stark inequalities across the country, with people living in the most deprived areas having almost double the incidence rate of head and neck cancer and more likely to be diagnosed at a late stage compared to those living in the least deprived areas.

Dr Valeria Mercadante, NIHR Clinical Lecturer/Academic StR and study investigator, commented: "We expect the number of patients with debilitating radiation-induced dry mouth to increase in the next few years, with most of them coming from deprived areas.”

The AQUAx2 study runs across multiple UCLH sites including the RN ENT & Eastman Dental Hospitals, the NIHR Clinical Research Facility at UCLH, the Macmillan Cancer Centre and further support from Imaging, Pharmacy and Cardiology.

Current standard of care treatments for dry mouth of radiotherapy have limited efficacy, are burden by adverse effects, and rely on the presence of residual functional salivary gland tissue. There has been no new treatment introduced for this group of patients for the last 20 years.

Professor Fedele said: "I am incredibly proud to be part of this research. It tackles an unmet need and offers UCLH patients a new regenerative medicine intervention that we hope will revolutionise the treatment of this debilitating, and so far considered irreversible, condition. Setting up this study has been a team effort and it would have not been possible to deliver it without the help and hard work of multiple UCLH staff and committees, as well as the NIHR UCLH BRC, to whom I am very grateful."

Patient story

Nathaniel Rackowe, a visual artist based in London, is the first person to receive the therapy on the trial. He said: “Professor Fedele mentioned the research during a visit to his clinic, and after discussion with him I thought it had much potential benefit to some of the side effects of my cancer treatment.

“I hope that the trials are successful, not only for myself to benefit from the treatment, but also to help others in my position… I’m really hoping this new procedure can help post cancer life for many people.”

Nathaniel makes sculpture and light installations. His newest work is open to the public outside Royal Festival Hall, commissioned by the Southbank Centre, until the end of January 2025.