Although the diagnosis of actinic keratosis (AK) has been associated with developing cutaneous squamous cell carcinoma (CSCC), patient age was shown to have a greater association with the long-term development of CSCC, according to the results of a 10-year longitudinal cohort study published in JAMA Dermatology.

The study authors explained that AK develops from sun exposure, and sun exposure is a “key” risk factor for CSCC. “Estimates of the risk of CSCC after AK diagnosis have been based on short-term studies,” they proposed as a rationale for conducting the study. 

The retrospective cohort study included 220,236 patients with AK and 220,236 matched patients without a diagnosis of AK. Patients were followed for up to 10 years, and clinical information was extracted from electronic medical records. 

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Overall, 19,620 (8.9%) of the patients with AK and 7095 (3.2%) of the patients without AK developed CSCC during follow-up, which translated to a nearly 2-fold greater likelihood of developing CSCC among patients with AK compared with those without AK (subdistribution hazard ratio [HR], 1.90; 95% CI, 1.85-1.95).

Among patients younger than 49 years, those with AK had a nearly 7-times greater likelihood of developing CSCC than patients without AK (HR, 6.77; 95% CI, 5.50-8.32).

The study also revealed that at 10 years, patients with AK had a 17.1% cumulative incidence of CSCC (95% CI, 16.9%-17.4%) compared with 5.7% (95% CI, 5.5%-5.9%) among patients without AK.

Older patients with AK reached the 10% cumulative incidence threshold for CSCC sooner than younger patients with AK. For instance, among patients with AK, those in their 50s reached the threshold between 7 and 8 years while those in their 80s reached the threshold between 1 and 2 years.

“The results of this longitudinal cohort study can be used to develop recommendations to increase early detection of CSCC,” the study authors concluded. They added that “Additional research is needed to understand the effect of AK treatment on the CSCC risk and outcomes of CSCC.”

Disclosure: Several study authors declared affiliations with the medical insurance industry. Please see the original reference for a full list of authors’ disclosures.


Madani S, Marwaha S, Dusendang JR, et al. Ten-year follow-up of persons with sun-damaged skin associated with subsequent development of cutaneous squamous cell carcinoma. JAMA Dermatol. Published online March 24, 2021. doi:10.1001/jamadermatol.2021.0372