Date of Award

January 2026

Document Type

Open Access Thesis

Degree Name

Medical Doctor (MD)

Department

Medicine

First Advisor

Sean Christensen

Abstract

BackgroundKeratinocyte carcinoma (KC), including cutaneous squamous cell carcinoma (SCC) and basal cell carcinoma (BCC), is the most common malignancy in the United States and is largely attributable to cumulative ultraviolet radiation exposure. Actinic keratoses (AKs) are premalignant lesions that arise within chronically sun-damaged skin and reflect the broader process of field cancerization. While AKs are recognized as markers of SCC risk, variability in clinical and histopathologic grading systems has limited their utility for standardized risk prediction. Improved classification of AKs may enable more accurate identification of patients at highest risk for KC, particularly SCC.

MethodsWe evaluated the association between AK severity and KC burden using both histologic and clinical approaches. Histologic assessment was performed in 106 adults undergoing Mohs micrographic surgery for head and neck tumors, grading histologic AK severity in tumor-free surgical margins using three systems: keratinocytic intraepidermal neoplasia (KIN), downward proliferation (PRO), and a novel area-based scale quantifying surface involvement. Clinical assessment was conducted in a multicenter cohort of 338 patients using the Field Cancerization Severity Tool (FAST). 62 patients were assessed using counts of discrete AKs and evaluation of confluent AK fields. Linear regression analyses were used to examine associations between grading measures and history of KC.

ResultsIncreasing histologic AK severity was significantly associated with increased burden of SCC and SCC in situ, but not BCC. Clinical measures capturing field cancerization, including higher FAST stage, greater AK counts, and presence of confluent AKs, were associated with SCC history. These associations were more pronounced among immunosuppressed patients, who demonstrated both higher AK severity scores and increased SCC burden.

ConclusionBoth histologic and clinical classifications of actinic damage correlate with SCC burden and provide complementary information for KC risk stratification. Incorporating standardized assessments of field cancerization into clinical practice may improve identification of high-risk patients and inform targeted surveillance and preventive strategies for SCC.

Comments

This is an Open Access Thesis.

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