Ten-Year Follow-up of Persons With Sun-Damaged Skin Associated With Subsequent Development of Cutaneous Squamous Cell Carcinoma | Dermatology | JAMA Dermatology | JAMA Network
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Original Investigation
March 24, 2021

Ten-Year Follow-up of Persons With Sun-Damaged Skin Associated With Subsequent Development of Cutaneous Squamous Cell Carcinoma

Author Affiliations
  • 1Department of Dermatology and Mohs Surgery, Kaiser Permanente, Walnut Creek, California
  • 2Department of Dermatology, Kaiser Permanente, Sacramento, California
  • 3Division of Research, Kaiser Permanente, Oakland, California
  • 4Department of Dermatology, Kaiser Permanente, Santa Clara, California
  • 5Department of Dermatology, Kaiser Permanente, San Jose, California
JAMA Dermatol. Published online March 24, 2021. doi:10.1001/jamadermatol.2021.0372
Key Points

Question  What is the risk of cutaneous squamous cell carcinoma after diagnosis of actinic keratosis (AK) during long periods of follow-up?

Findings  In this cohort study, in a community-based population in California, the risk of cutaneous squamous cell carcinoma was 1.92% per year after diagnosis of 1 or more AKs and 0.83% per year without an AK diagnosis, with older age being a stronger risk factor than AK diagnosis.

Meaning  These results can be used to develop recommendations for risk-based patient education, treatment, and surveillance.


Importance  Risk of cutaneous squamous cell carcinoma (cSCC) after the diagnosis of actinic keratosis (AK) has not been studied during long follow-up periods.

Objective  To estimate the risk up to 10 years and identify risk factors for cSCC development.

Design, Setting, and Participants  This longitudinal cohort study, performed from January 1, 2009, to February 29, 2020, examined Kaiser Permanente Northern California patients with AK and control patients matched 1:1 on age, sex, race/ethnicity, medical center, and date of the initial diagnosis plus 30 days in the patients with AK.

Exposures  Patients with AK and control participants were followed up for up to 10 years for incidence of cSCC.

Main Outcomes and Measures  Incident cSCC was obtained from pathologic data, and subdistribution hazard ratios (HRs) and 95% CIs were estimated using Cox proportional hazards regression analysis, accounting for competing risks, calendar year, demographic factors, and number of AKs.

Results  The study included 220 236 patients with AK and 220 236 matched control patients (mean [SD] age, 64.1 [12.2] years; 231 248 [52.5%] female). After losses to follow-up were accounted for, risk of cSCC increased with each year of follow-up by 1.92% (95% CI, 1.89%-1.95%) in patients with AK and 0.83% (95% CI, 0.81%-0.85%) in matched control patients (subdistribution HR, 1.90; 95% CI, 1.85-1.95). However, among patients 49 years or younger, those diagnosed with AK were nearly 7 times more likely to be diagnosed with cSCC than those without AK (HR, 6.77; 95% CI, 5.50-8.32). At 10 years, the cumulative incidence of cSCC reached 17.1% (95% CI, 16.9%-17.4%) in patients with AK and 5.7% (95% CI, 5.5%-5.9%) in control patients. Increased numbers of AKs were modestly associated with increased cSCC risk (≥15 AKs vs 1 AK: subdistribution HR, 1.89; 95% CI, 1.75-2.04). Older patients had much higher risk of cSCC than younger patients (compared with those ≤49 years of age at AK diagnosis; ≥80 years of age: subdistribution HR, 8.18; 95% CI, 7.62-8.78). Other than AK, risk factors for cSCC included older age, White race (a proxy for skin type), history of basal cell carcinoma, and male sex. Risk decreased between 2009 and 2019 (2018-2019 vs 2009-2010: subdistribution HR, 0.67; 95% CI, 0.63-0.72).

Conclusions and Relevance  The results of this longitudinal cohort study can be used to develop recommendations to increase early detection of cSCC. Additional research is needed to understand the effect of AK treatment on cSCC risk and outcomes of cSCC.

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