High risk of cutaneous squamous cell carcinoma in patients with actinic keratosis

May 2022 Cancer trials Nalinee Pandey
Human squamous cell carcinoma. Tissues affected by cancer cells under a microscope.

A recent investigation reports that patients with Olsen grade III actinic keratosis (AK) are more likely to develop cutaneous squamous cell carcinoma (cSCC). These findings were reported in the journal JAMA dermatology.

AK is a skin disorder with a global prevalence of 11 to 60%, and it is believed to result in invasive cSCC. Also, it is not well known if the treatment of AK decreases the risk of cSCC. Researchers at the Department of Dermatology at Maastricht University Medical Center in the Netherlands have evaluated the risk of cSCC in patients with AK.

Study Design

The study analysed data from a randomised clinical trial comparing 4 filed directed AK treatments. The trial enrolled 624 patients randomly assigned into four treatment groups, i.e. 5% fluorouracil cream, 5% imiquimod cream, methylamino levulinate PDT, or 0.015% ingenol mebutate gel. The study’s primary endpoint was to evaluate the proportion of patients who developed invasive cSCC. The secondary endpoint was the association between the risk of invasive cSCC and prior defined prognostic factors.


After a follow up from July 2019 to December 31, 2020, 26 out of 624 enrolled participants developed invasive cSCC. The total four-year risk of developing cSCC in the previously treated area of AK was 3.7% (95% CI, 2.4%-5.7%). The risk was highest in patients treated with imiquimod (5.8%) and lowest in those treated with fluorouracil (2,2%).

Importantly, it was found that patients with severe AK (Olsen grade III) had an increased risk of 20.9% (95% CI, 10.8%-38.1%), and it was increased to 33.5% (95% CI, 18.2%-56.3%) in patients requiring additional treatment.


The secondary analysis of a randomised clinical trial suggests an increased risk of cSCC in patients with AK that was increased further in those who required additional treatment.


Ahmady S, Jansen MHE, Nelemans PJ, et al. Risk of Invasive Cutaneous Squamous Cell Carcinoma After Different Treatments for Actinic Keratosis: A Secondary Analysis of a Randomized Clinical Trial. JAMA Dermatol.