Natural History of Incident and Persistent Cutaneous Human Papillomavirus and Human Polyomavirus Infections.

BACKGROUND: Cutaneous human papillomaviruses (cuHPV) and polyomaviruses (HPyV) have been implicated in skin cancers; however, interpretation of findings across studies is complicated by limited understanding of the natural history of these infections across normal tissue types. METHODS: In total, 675 eyebrow hair (EBH) and skin swab (SSW) samples were collected from 71 skin cancer screening patients every 6 months over 2 years and measured for presence of ß-HPV, γ-HPV, and HPyV. Incidence, persistence, and clearance of cuHPV/HPyV were estimated, and risk factors associated with infection were examined. RESULTS: Prevalence, incidence, and persistence of ß-HPV, γ-HPV, and HPyV were consistently higher in SSW than in EBH, with types 5, 24, 49, 76 and Merkel cell polyomavirus (MCPyV) having incidence rates greater than 20 per 1000 person-months. Prevalent γ-HPV EBH infections persisted more often in women (P = .024), incident ß-HPV EBH infections persisted less often among individuals with history of blistering sunburn (P = .019), and prevalent MCPyV SSW infections persisted more often in those with a history of skin cancer (P = .033). CONCLUSIONS: Incidence and persistence of cuHPV/HPyV were observed in SSW and EBH; however, none of the risk factors examined were commonly associated with cuHPV/HPyV infections across normal tissue types.

Circulating Immunosuppressive Regulatory T Cells Predict Risk of Incident Cutaneous Squamous Cell Carcinoma.

Ultraviolet radiation exposure (UVR) is a risk factor for cutaneous squamous cell carcinoma (cuSCC) and has been shown to be positively associated with circulating immunosuppressive regulatory T cells ("Tregs"). However, the risk of cuSCC in association with circulating Tregs has not been studied. The aim of this study was to determine whether circulating Treg levels are associated with cuSCC development, particularly in the context of high UVR. Blood and spectrophotometer-based UVR measurements were obtained on 327 immunocompetent individuals undergoing routine skin cancer screenings at baseline and followed for up to 4 years for incident cuSCC development within a prospective cohort study. Proportions of phenotypically distinct Tregs, especially CCR4hi and CLA+ cells which are associated with activation and homing, respectively, were measured by flow cytometry. Tregs in cuSCC tumors were assessed using immunohistochemistry and graded for solar elastosis, a measure of cumulative UVR damage. Of several Treg phenotypes examined, higher levels of circulating CCR4hi Tregs at baseline were significantly associated with increased risk of subsequent cuSCC; those with higher levels of both CCR4hi and UVR were four times more likely to develop cuSCC compared to those with lower levels of both (Hazard Ratio = 4.11, 95% CI = 1.22-13.90). Within cuSCC tumors, CCR4hi Tregs were positively associated with solar elastosis. Results show that a higher proportion of CCR4hi peripheral Tregs predicts incident cuSCC up to 4 years, especially among highly UV-exposed individuals. Research of the underpinning biology of Tregs in UVR-associated skin damage may possibly reveal novel opportunities for screening, prevention, and treatment.

Cutaneous Human Papillomaviruses and the Risk of Keratinocyte Carcinomas.

Cutaneous human papillomavirus (cuHPV) infections may be novel targets for skin cancer prevention and treatment, but critical information regarding the development of virus-positive skin cancers following cuHPV infection has been lacking. In this study, baseline cuHPV infection was measured by serology and viral DNA detection in eyebrow hairs (EBH) and forearm skin swabs (SSW) among 1,008 individuals undergoing routine skin cancer screening exams and followed for incidence of basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cuSCC). Baseline ß-HPV detection, particularly in SSW, significantly predicted cuSCC (HR = 4.32; 95% confidence interval, 1.00-18.66), whereas serologic evidence of past ß-HPV infection was not associated with cuSCC. Less than 5% of baseline ß-HPV types detected in SSW were present in subsequent cuSCC tumors, and cuHPV detected in SSW with higher mean fluorescence intensity values were more likely to be present in cuSCC compared with those with lower levels (P < 0.001). ß-HPV-positive cuSCC occurred more often in areas of highly sun-damaged skin than did ß-HPV-negative cuSCC. Overall, no clear patterns were observed between baseline ß-HPV detection and subsequent development of BCC, or between baseline γ-HPV detection and either cuSCC or BCC. Collectively, these results demonstrate that ß-HPV detection in SSW is a significant predictor of cuSCC risk, although evidence suggests only a small subset of cuSCC is etiologically linked to ß-HPV infection. SIGNIFICANCE: ß-HPV positivity may be a useful biomarker for identifying individuals who could benefit from increased screening or novel cutaneous squamous cell carcinoma prevention strategies.

Association between Human Polyomaviruses and Keratinocyte Carcinomas: A Prospective Cohort Study.

BACKGROUND: A positive association between Merkel cell polyomavirus (MCPyV) infection and cutaneous squamous cell carcinoma (cuSCC) has been observed in at least one previous case-control study. To evaluate this association in a prospective context, we investigated infections with human polyomaviruses (HPyV), including MCPyV, as predictors of keratinocyte carcinomas, including cuSCC and basal cell carcinoma (BCC), among a cohort of immunocompetent individuals enrolled in the Viruses in Skin Cancer (VIRUSCAN) Study. METHODS: Associations between markers of baseline HPyV infection (serum antibodies and viral DNA in eyebrow hairs and skin swabs) and incident keratinocyte carcinomas were modeled using Cox proportional hazards regression. Proportions of baseline HPyV infections that were concordant with a subsequent tumor positive for the same HPyV type were assessed. RESULTS: No significant associations were observed between baseline markers of MCPyV or other HPyV infections and cuSCC or BCC. Less than 4.5% of baseline MCPyV infections were also detected in subsequently developed keratinocyte carcinoma tumors. CONCLUSIONS: HPyV infection was not a predictor of keratinocyte carcinoma risk in this prospective cohort. IMPACT: Cancer-associated infections represent attractive targets for cancer prevention; however, HPyV infections have limited potential as novel targets for cuSCC prevention.

Cutaneous viral infections associated with ultraviolet radiation exposure.

The complex interplay between ultraviolet radiation (UVR) and cutaneous viral infections in the context of cancer etiology is challenging to unravel, given the limited information on the independent association between UVR and cutaneous viral infections. Using multiple biomarkers of infection with 24 types of cutaneous human papillomavirus (HPV) and 4 types of polyomaviruses (HPyV), we investigated cross-sectional associations with recent UVR exposure, using skin pigmentation measured by spectrophotometer. Age- and sex-adjusted associations between UVR and viral seropositivity, viral DNA present in eyebrow hairs (EBH) and skin swabs (SSW) were estimated using logistic regression. Beta-HPV seropositivity was associated with viral DNA positivity in EBH (OR = 1.40, 95% CI = 1.05-1.88) and SSW (OR = 1.86, 95% CI = 1.25-2.74). Similar associations were observed for Merkel cell polyomavirus. Participants in the highest tertile of UVR exposure were more likely to be seropositive for beta-HPV (OR = 1.81, 95% CI = 1.16-2.38), and have beta-HPV DNA in EBH (OR = 1.57, 95% CI = 1.06-2.33) and SSW (OR = 2.22, 95% CI = 1.25-3.96), compared to participants with the lowest tertile of UVR exposure. UVR exposure was positively associated with three different markers of beta-HPV infection. Therefore, future studies of HPV associated KC development should address more directly the role of HPV and UVR exposure as potential co-carcinogens.

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.

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.

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.

Submammary Granular Parakeratosis Treated With Mastopexy.

Granular parakeratosis, originally named axillary granular parakeratosis, is an uncommon disease with an unclear etiology. It is thought to result from defective processing of profillagrin to fillagrin, causing retention of keratohyaline granules in the epidermis. A myriad of causative factors has been proposed, including friction, moisture, heat, and contact irritants such as deodorants. We present a case in the inframammary area that resolved with mastopexy, further supporting the role of friction, moisture, and heat. Furthermore, we present electron microscopic evidence demonstrating non-degraded keratohyaline granules upon epidermal maturation. This entity, we believe, is reactive and represents a protective response of the body to moisture and heat.

J Drugs Dermatol. 2017;16(8):810-812.

Isolation and characterization of a novel putative human polyomavirus.

The small double-stranded DNA polyomaviruses (PyVs) form a family of 73 species, whose natural hosts are primarily mammals and birds. So far, 13 PyVs have been isolated in humans, and some of them have clearly been associated with several diseases, including cancer. In this study, we describe the isolation of a novel PyV in human skin using a sensitive degenerate PCR protocol combined with next-generation sequencing. The new virus, named Lyon IARC PyV (LIPyV), has a circular genome of 5269 nucleotides. Phylogenetic analyses showed that LIPyV is related to the raccoon PyV identified in neuroglial tumours in free-ranging raccoons. Analysis of human specimens from cancer-free individuals showed that 9 skin swabs (9/445; 2.0%), 3 oral gargles (3/140; 2.1%), and one eyebrow hair sample (1/439; 0.2%) tested positive for LIPyV. Future biological and epidemiological studies are needed to confirm the human tropism and provide insights into its biological properties.

Cutaneous Human Papillomavirus Infection and Development of Subsequent Squamous Cell Carcinoma of the Skin.

The role of cutaneous human papillomavirus (HPV) infection in the development of subsequent cutaneous squamous cell carcinoma (SCC) is unknown. Pathologically confirmed cases of SCC (n = 150) enrolled in a previously conducted case-control study were included in a retrospective cohort study to examine the association of cutaneous HPV at the time of SCC diagnosis with the risk of subsequent SCC development. Data on HPV seropositivity, HPV DNA in eyebrow hairs (EB) and SCC tumors were available from the parent study. Incidence of subsequent SCC was estimated using person-years of follow up. Cox Proportional Hazards ratios were estimated to evaluate the associations of both, HPV seropositivity and HPV DNA positivity with subsequent SCC. The five year cumulative incidence of subsequent SCC was 72%. Seropositivity to cutaneous HPV was not associated with the risk of subsequent SCC (HR = 0.83, 95% CI = 0.41-1.67). Any beta HPV infection in EB was associated with reduced risk (HR = 0.30, 95% CI = 0.11-0.78) of subsequent SCC among cases who were positive for beta HPV DNA in tumor tissue. Infection with beta HPV type 2 (HR = 0.32, 95% CI = 0.12-0.86) in EB was associated with reduced risk of subsequent SCC among HPV DNA positive SCCs. In conclusion, beta HPV infection was inversely associated with the risk of subsequent SCC.

IgG4-related skin disease may have distinct systemic manifestations: a systematic review.

IgG4-related disease (IgG4-RD) is an increasingly prevalent protean multisystem disorder characterized by single or multi-organ infiltration of IgG4-bearing plasma cells. Skin involvement has been recognized and is relevant to proper diagnosis. A systematic literature review of 50 cases involving the skin reveals that patients with IgG4-related skin disease show predominant involvement of the head and neck and have a distinct pattern of systemic involvement, also favoring the head and neck - lymphatics, orbit, salivary, and lacrimal glands - but generally lacking pancreaticobiliary involvement (16% of cases), which by contrast is a predominant manifestation in systemic IgG4-RD (60% with pancreaticobiliary involvement). We summarize clinical and pathologic descriptive data from this systematic review. We review differential diagnosis and propose a diagnostic scheme for stratifying probability of disease based upon comprehensive integration of clinical, histopathologic, and laboratory data. Plasmacyte infiltration and storiform fibrosis are prominent in IgG4-related skin disease, but obliterative venulitis is less common than in the prototypical IgG4-related disease manifestation of autoimmune pancreatitis. IgG4 tissue and serum values, with a mean (±95% CI) in the reviewed cases of 132.8 ± 32.6 IgG4-positive plasma cells per high-power field and 580 ± 183.8 mg/dl, respectively, are incorporated into the suggested criteria. The distinct set of manifestations identified by this systematic review and the proposed diagnostic considerations, while requiring further validation in prospective studies, highlight the need to consider that IgG4-related skin disease defines a unique systemic disease complex along the spectrum of IgG4-RD.

Merkel cell polyomavirus (MCV) T-antigen seroreactivity, MCV DNA in eyebrow hairs, and squamous cell carcinoma.

BACKGROUND: The role of Merkel cell polyomavirus (MCV) infection in the etiology of non-melanoma skin cancers, other than Merkel cell carcinoma, is unclear. Previously, we reported a significant association between seropositivity to MCV capsid antigen and MCV DNA-positive cutaneous squamous cell carcinoma (SCC). Here we present associations between SCC and seroreactivity to MCV T-antigen (T-Ag) oncoprotein, as well as MCV DNA detected in eyebrow hairs. FINDINGS: A clinic-based case-control study, including 171 SCC cases and 300 controls without skin cancer, was conducted at Moffitt Cancer Center in Tampa, Florida. Multiplex assays were used to measure serum antibodies against MCV small and large T-Ag and MCV DNA in both eyebrow hairs and SCC tumors (n = 144). Odds ratios (ORs) and 95 % confidence intervals (CIs) were estimated using logistic regression to evaluate the associations between MCV and SCC. No significant association was observed between seroreactivity to MCV full-length large or small T-Ag and SCC, overall [ORlarge T-Ag = 0.99 (0.48-2.08), ORsmall T-Ag = 0.31 (0.06-1.62)] or when comparing tumor MCV DNA-positive cases to controls [ORlarge T-Ag = 1.06 (0.38-2.93)]. Only presence of MCV DNA in eyebrow hairs was significantly associated with MCV DNA-positive SCC [OR = 4.05 (2.01-8.18)]. CONCLUSION: MCV infection is unlikely to play a direct role in SCC.

Case-control study of genus-beta human papillomaviruses in plucked eyebrow hairs and cutaneous squamous cell carcinoma.

Cutaneous human papillomaviruses (HPV) have been reported in cutaneous squamous cell carcinoma (SCC). We conducted a clinic-based case-control study to investigate the association between genus-beta HPV DNA in eyebrow hairs (EBH) and SCC. EBH from 168 SCC cases and 290 controls were genotyped for genus-beta HPV DNA. SCC tumors from a subset of cases (n = 142) were also genotyped. Viral load was determined in a subset of specimens positive for a single HPV type. Associations with SCC were estimated by odds ratios (OR) and 95% confidence intervals (CI) adjusted for age and sex using logistic regression. Statistical tests were two-sided. EBH DNA prevalence was greater in cases (87%) than controls (73%) (p < 0.05), and the association with SCC increased with the number of HPV types present, (≥ 4 types vs. HPV-negative: OR = 2.02, 95% CI = 1.07-3.80; p(trend) = 0.02). Type-specific associations were observed between SCC and DNA in EBH for HPV23 (OR = 1.90, 95% CI = 1.10-3.30) and HPV38 (OR = 1.84, 95% CI = 1.04-3.24). Additionally, when compared with the controls, the DNA prevalence in EBH was significantly higher among cases for 11 of the 25 genus-beta types tested, when accounting for DNA for the same HPV type in the tumor (ORs = 3.44-76.50). Compared to controls, the mean viral DNA load in EBH among the selected cases was greater for HPV5, HPV8 and HPV24, but lower for HPV38. SCC cases were more likely than controls to have HPV DNA+ EBH for single and multiple HPV types, providing additional support for the potential role of genus-beta HPV infections in SCC development.

Spotlighting the role of photodynamic therapy in cutaneous malignancy: an update and expansion.

BACKGROUND: Topical photodynamic therapy (PDT) is an option for the treatment of cutaneous malignancy. OBJECTIVE: To present an update and expansion on a previous review of the use of PDT in the current literature in the treatment of actinic keratoses (AK), superficial and nodular basal cell carcinoma (sBCC, nBCC), squamous cell carcinoma (SCC), Bowen's disease, cutaneous T cell lymphoma (CTCL), malignant melanoma, and its use in chemoprevention. METHODS: Extensive PubMed search January 2013. RESULTS AND CONCLUSIONS: We find sufficient evidence to recommend the use of PDT in certain patients in the treatment of AK, Bowen's disease, sBCC, and nBCC. It is especially useful in those with contraindications to surgery, widespread areas of involvement, and large lesions. Not only can it be considered superior to other therapies as far as recovery time, tolerance, and cosmetic outcomes, but it also should be considered, when indicated, as first-line treatment in the above conditions. Investigations continue for the use of PDT in the treatment of melanoma, SCC, chemoprevention, and CTCL.

Telomere length and risk of melanoma, squamous cell carcinoma, and basal cell carcinoma.

BACKGROUND: Telomeres help maintain chromosomal structure and may influence tumorigenesis. We examined the association between telomere length and skin cancer in a clinic-based case-control study of 198 melanoma cases, 136 squamous cell carcinoma (SCC) cases, 185 basal cell carcinoma (BCC) cases, and 372 healthy controls. METHODS: Cases were histologically confirmed patients treated at the Moffitt Cancer Center and University of South Florida Dermatology Clinic in Tampa, FL. Controls self-reported no history of cancer and underwent a skin cancer screening exam at study enrollment to rule out the presence of skin cancer. Quantitative real time PCR was used to measure telomere length in peripheral blood samples. RESULTS: Melanoma patients had longer telomeres than controls (odds ratio (OR)=3.75; 95% confidence interval (CI): 2.02-6.94 for highest versus lowest tertile) (P for trend=<0.0001). In contrast, longer telomere length was significantly inversely associated with SCC (OR=0.01; 95% CI: 0.00-0.05 for highest versus lowest tertile) (P for trend=<0.0001) and BCC (OR=0.10; 95% CI: 0.06-0.19 for highest versus lowest tertile) (P for trend=<0.0001). CONCLUSION: Telomere length may be involved in the development of skin cancer, although the effect on cancer risk differs for melanoma and non-melanoma carcinomas. Our findings suggest that long telomere length is positively associated with melanoma while inversely associated with SCC and BCC.

Case-control study of cutaneous human papillomavirus infection in Basal cell carcinoma of the skin.

Genus-ß human papillomavirus (HPV) DNA has been detected in basal cell carcinoma (BCC) tumors, but most epidemiologic studies have not observed associations between genus-ß HPV seropositivity and BCC. A clinic-based case-control study was conducted to investigate cutaneous HPV infection in BCC. BCC cases (n=224) were recruited from a dermatology clinic, and controls (n=300) were patients who were screened negative for skin cancer. Antibodies against cutaneous HPV types in genera α, ß, γ, mu, and nu were measured, and tumors from a subset of BCC cases (n=195) were tested for HPV DNA. Overall associations were observed between BCC and seropositivity for HPV types in genus-α (odds ratio (OR)=1.61; 95% confidence interval (CI)=1.11-2.35), γ (OR=1.78; 95% CI=1.22-2.60), and mu (OR=1.56; 95% CI=1.06-2.30). BCC cases with ß-HPV DNA in their tumors were more likely to be ß-HPV seropositive than controls (OR=1.76; 95% CI=1.03-3.01), with type-specific associations observed for HPV8 and HPV23, whereas no association was observed between ß-HPV seropositivity and ß-HPV DNA-negative BCC. No concordance between seropositivity and tumor DNA status was observed for HPV types in genera α and γ. In conclusion, the combined serology and tumor DNA results suggest that ß HPV types may have a role in BCC. Additional studies of BCC that assess HPV types in multiple genera are needed.

Patterns and timing of sunlight exposure and risk of basal cell and squamous cell carcinomas of the skin--a case-control study.

BACKGROUND: Non-melanoma skin cancer (NMSC), comprised of basal (BCC) and squamous (SCC) cell carcinomas, is the most common cancer in Caucasians. Ultraviolet radiation (UVR) exposure is the most important environmental risk factor for NMSC. However, the precise relationship between UVR and the risk of NMSC is complex, and the relationship may differ by skin cancer type. METHODS: A case-control study was conducted among Florida residents to investigate measures of patterns (intermittent vs. continuous) and timing (childhood vs. adulthood) of sunlight exposure in BCC and SCC. Participants included 218 BCC and 169 SCC cases recruited from a university dermatology clinic and 316 controls with no history of skin or other cancers. RESULTS: A history of blistering sunburn (a measure of intermittent sunlight exposure) was associated with both BCC (OR = 1.96, 95% CI = 1.27-3.03) and SCC (OR = 2.02, 95% CI = 1.22-3.33). Additionally, having a job in the sun for ≥ 3 months for 10 years or longer (a measure of continuous sunlight exposure) was also associated with both BCC and SCC in our study population. With the exception of younger age at first blistering sunburn, measures of younger age at sunlight exposure tended to be associated with SCC, but not BCC risk. CONCLUSIONS: Results from the current study suggest that sunlight exposure is associated with both BCC and SCC risk regardless of the pattern in which the exposure was received (i.e. intermittent vs. continuous). The data also suggest that sunlight exposure at a younger age may be more important for SCC but not BCC, however additional studies are needed to further characterize sunlight exposure-response relationships in different types of NMSC.