Skin cancer rates continue to rise across the UK, and people who are immunocompromised, which means they have a weakened immune system, face an even greater risk. They’re particularly vulnerable to developing squamous cell carcinoma (SCC), a type of non-melanoma skin cancer.  

In the general population, SCC usually grows slowly and rarely spreads. But being immunocompromised can change that. People with a weakened immune system are not only more likely to develop SCC, but they’re also more likely to experience multiple skin cancers over time, and they’re at increased risk of SCC spreading to other parts of the body.

That’s why Professor Catherine Harwood and Professor Rubeta Matin are leading a new clinical trial called SPOT-IT. They want to answer an important question: how can we best prevent SCC in people with the highest risk?

Mind the prevention gap

Most squamous cell skin cancers appear on areas of skin that are frequently exposed to the sun, such as the head, neck, forearms, and the backs of the hands. They can also develop in places where the skin has been damaged before, including old scars, burns, or long-standing ulcers.

For immunocompromised people (for example, people who have had an organ transplant), the risk of developing SCC is much higher. That’s because the immune system plays a vital role in detecting, repairing and eliminating skin cells damaged by UV radiation. When that system is weakened, multiple protective mechanisms are lost at once.

This also makes immunocompromised people more prone to developing multiple SCCs over time. As a result, they may need to go through repeated surgeries, which can have a major impact on their daily life and overall wellbeing.

“Although most of these cancers can be treated surgically, repeated operations can have a significant impact,” says Harwood. “They can affect appearance, function and confidence, particularly when cancers occur on visible areas like the face and hands. Over time, this takes a real toll on people’s quality of life.”

Currently, doctors recommend that, like everyone else, immunocompromised people should use sunscreen regularly to lower their risk of skin cancer. But Harwood, Matin and their team have specifically designed SPOT-IT to find a way for people with the highest SCC risk to protect themselves even more effectively.

“Immunocompromised people, such as organ transplant recipients, are often underrepresented in clinical trials, which means prevention strategies are frequently based on evidence from people with normal immune systems,” explains Matin.

Protecting high-risk people from squamous cell carcinoma 

To develop a prevention strategy, the research team aren’t starting from scratch. They’re looking at tools already used to treat or manage skin changes that could lead to cancer (pre-cancerous lesions) called actinic keratoses (AK). 

There are several tools we already know can treat or manage AK and help lower the risk of SCC. Previous studies in Australia have shown that using sunscreen regularly can help protect the general population against both AK and SCC. There’s also a cream containing the chemotherapy drug 5-fluorouracil (5‑FU) that can be used to directly treat sun-damaged skin and AK spots, so there’s less of a chance they might turn into SCC. However, 5‑FU cream can be tricky to use. It often causes redness, pain, and crusting, and can leave skin looking and feeling irritated for several weeks after treatment.

Recently, researchers found that combining 5‑FU cream with a vitamin D-based ointment called calcipotriol can shorten the time needed for treatment. With this combination, people only need to apply the creams for 4 to 6 days, and any side effects usually settle down more quickly. Patients who tried this shorter treatment also found it easier to manage.

Although these treatments have been tested in the general population, they haven’t been studied on a large scale in immunocompromised people. So, SPOT-IT will compare all three options: daily sunscreen, sunscreen and 5‑FU, and sunscreen with 5‑FU combined with calcipotriol, to see which works best at preventing future SCCs in this high-risk group.

Each person joining the study has already experienced at least one invasive SCC recently, and many know all too well how often these cancers can return. By testing these three prevention approaches against each other, the SPOT-IT team hopes to find out which is the best option for protecting people in the years ahead. 

“What’s unusual about this study is that the outcomes won’t only benefit future patients, but potentially also the participants who are taking part in this trial later in their lives,” Harwood explains. “Because patients tend to develop more of these skin cancers over time, identifying the right prevention strategy really matters over the course of a lifetime.”

Reducing cancer risk with fewer side effects 

Although 5-FU cream can be an effective way to stop SCC, it can also cause weeks of redness, peeling and discomfort, which means some people struggle to complete their treatment.

That’s why combining 5-FU cream with a vitamin D ointment to help shorten the treatment time could be so important. In cases like this, finding what’s effective only solves part of the problem. A preventative treatment can only have an impact if people are able and willing to use it.

And finding the best overall option is even more vital when people have a higher cancer risk. Harwood knows how much of a difference focusing on immunocompromised people, who are most in need of a precise and targeted approach to preventing SCC, could make.

“I care for patients whose transplants are working perfectly, yet they’re coming back to the hospital every few months to have skin cancers removed,” she says. ”It’s an ongoing burden that sits alongside what should otherwise be a hugely positive outcome from their transplant.”

That’s exactly what SPOT-IT aims to change.

“This research is a first step towards changing how we prevent skin cancer in immunocompromised patients,” explains Harwood. “With the right evidence, we can move towards more personalised, effective prevention and reduce the long‑term burden of this disease.”

By developing approaches that are both effective and tolerable, Harwood, Matin and their team are laying the foundation for a future where life after transplant can be lived with confidence, not constant concern.