T Regulatory Cell Subpopulations Associated with Recent Ultraviolet Radiation Exposure in a Skin Cancer Screening Cohort.

UV radiation (UVR) causing DNA damage is a well-documented risk factor for nonmelanoma skin cancer. Although poorly understood, UVR may also indirectly contribute to carcinogenesis by promoting immune evasion. To our knowledge, we report the first epidemiological study designed to investigate the association between quantitative measures of UVR, obtained using a spectrophotometer, and circulating T regulatory (Treg) cells. In addition to total Treg cells, the proportion of functionally distinct Treg cell subsets defined by CD45RA and CD27 phenotypic markers, graded expression of FOXP3 and CD25, and those expressing cutaneous lymphocyte-associated Ag and the chemokine receptor CCR4 were enumerated in 350 individuals undergoing routine skin cancer screening exams and determined not to have prevalent skin cancer. No associations were identified for UVR exposure or the overall proportion of circulating Treg cells; however, Treg cell subpopulations with an activation-associated phenotype, CD45RA-/CD27-, and those expressing cutaneous homing receptors were significantly positively associated with UVR. These subpopulations of Treg cells also differed by age, sex, and race. After stratification by natural skin tone, and adjusting for age and sex, we found that spectrophotometer-based measures of UVR exposure, but not self-reported measures of past sun exposure, were positively correlated with the highest levels of these Treg cell subpopulations, particularly among lighter-skinned individuals. Findings from this large epidemiologic study highlight the diversity of human Treg cell subpopulations associated with UVR, thus raising questions about the specific coordinated expression of CD45RA, CD27, CCR4, and cutaneous lymphocyte-associated Ag on Treg cells and the possibility that UVR contributes to nonmelanoma skin cancer carcinogenesis through Treg cell-mediated immune evasion.

Cutaneous Viral Infections Across 2 Anatomic Sites Among a Cohort of Patients Undergoing Skin Cancer Screening.

BACKGROUND: Findings from previous studies of cutaneous human papillomavirus (cuHPV) infection and keratinocyte carcinomas have varied due to several factors, including use of different sample types for cuHPV DNA detection. Elucidating the relationship between cuHPV infection in eyebrow hairs (EBHs) and skin swabs (SSWs) is critical for advancing the design of future studies. METHODS: DNA corresponding to 46 ß-HPV and 52 γ-HPV types was measured in EBHs and SSWs obtained from 370 individuals undergoing routine skin cancer screening examinations. RESULTS: Prevalence of ß-HPV/γ-HPV was 92%/84% and 73%/43% in SSWs and EBHs, respectively, with 71%/39% of patients testing positive for ß-HPV/γ-HPV in both sample types. Number of cuHPV types detected and degree of infection were correlated across SSWs and EBHs. When the EBH was positive for a given ß-HPV/γ-HPV type, the SSW was positive for that same type 81%/72% of the time. CONCLUSIONS: Testing SSWs captures more cuHPV infection than EBHs, with EBH infections usually representing a subset of SSW infections. The importance of optimizing sensitivity of cuHPV infection detection using SSWs vs specificity using EBHs (or a combination of the 2) will be ascertained in an ongoing cohort study investigating cuHPV associations with subsequent keratinocyte carcinomas.

Viruses in Skin Cancer (VIRUSCAN): Study Design and Baseline Characteristics of a Prospective Clinic-Based Cohort Study.

BACKGROUND: Accumulating evidence suggests that cutaneous viral infections are risk factors for the development of keratinocyte carcinomas. The Viruses in Skin Cancer (VIRUSCAN) Study, a prospective cohort study, was established in 2014 to investigate the risk of keratinocyte carcinoma associated with cutaneous human papillomavirus and polyomavirus infection and the possible interaction with ultraviolet radiation exposure (UVR). METHODS/RESULTS: VIRUSCAN incorporates repeated measures of viral infection using multiple markers of infection and quantitative measures of UVR using a spectrophotometer. Participants were recruited between July 14, 2014 and August 31, 2017 at the University of South Florida Dermatology Clinic in Tampa, FL. After excluding 124 individuals with prevalent keratinocyte carcinomas at baseline, 1,179 participants (53.2% women, 46.8% men, all ages 60 years and older) were followed for up to 4 years with routine skin exams occurring every 6 to 12 months. Here, we present the VIRUSCAN Study design, methods, and baseline characteristics, including demographics, sun exposure behavior, quantitative UVR exposure measurements, and cutaneous viral prevalence, for the full study cohort. CONCLUSIONS: The VIRUSCAN Study will provide critical temporal evidence needed to assess the causality of the role cutaneous viral infections play in the development of keratinocyte carcinomas, as well as the potential interaction between cutaneous viral infections and UVR exposure. IMPACT: Study findings will be valuable in future development of novel keratinocyte carcinoma prevention strategies.