MicroRNA Signatures Associated with Basal Cell Carcinoma Subtypes.

Basal cell carcinoma (BCC) is classified histologically into subtypes that determine treatment decisions. MicroRNAs (miRs) are short noncoding RNAs that may serve as diagnostic biomarkers. We investigated if particular miRs could distinguish BCC subtypes. We sequenced miRs from 55 archival BCC and 9 control skin specimens and then validated these miRs by qRT-PCR assay on a second BCC cohort (18 superficial, 16 nodular, 15 infiltrative) and control skin (n = 12). Expression values for individual miRs were normalized to miR-16-5p, which was the least variant among the control skin and BCC samples. We found that (i) miR-383-5p and miR-145-5p are downregulated in all BCC subtypes compared with control skin, (ii) miR-181c-5p is downregulated in superficial compared with invasive (nodular/infiltrative) BCC, and (iii) miR-22-5p and miR-708-5p are upregulated in infiltrative compared with superficial/nodular BCC and miR-30c-5p is downregulated in infiltrative compared with nodular BCC. Receiver operating characteristic analysis demonstrated excellent capacity of these miRs to discriminate between BCC and control skin (area under the curve, 0.94-0.98), whereas the capacity to discriminate between superficial and invasive subtypes was less robust (area under the curve, 0.7-0.8). Future prospective studies may determine the utility of these miRs as diagnostic biomarkers to guide biopsy and treatment of BCC.

Protocol for a cluster-randomized trial of a school-based skin cancer preventive intervention for adolescents.

BACKGROUND: Adolescents infrequently use sun protection and engage in intentional tanning more frequently compared to other age groups, leading to increased ultraviolet radiation (UVR) exposure that heightens skin cancer risk across the lifespan. High schools are therefore an ideal setting for offering skin cancer preventive interventions. Yet, there are limited UVR protection interventions for high school students, especially those that are personalized, tested using randomized designs, and include long-term outcome assessment to determine the durability of intervention effects. METHOD: The Sun-safe Habits Intervention and Education (SHINE) cluster-randomized trial will test a novel, personalized intervention that targets high school adolescents' sun protection and tanning behaviors, and tracks their outcomes for up to one year following intervention. Enrolled high schools will be randomized to receive either the personalized SHINE intervention, which includes facial UVR photographs and sun protection action planning, or standard education using publicly available materials. Students in both conditions will receive information about skin cancer, sun protection, and skin self-examination. Outcome variables will include students' sun protection and tanning behaviors and sunburn occurrence. Potential moderators (e.g., race/ethnicity) and mediators (e.g., self-efficacy) will also be assessed and tested. CONCLUSIONS: This trial examines the efficacy of a personalized intervention targeting sun protection and tanning of high school students. The project will lead to new scientific understanding of the theoretical mechanisms underlying outcomes and moderators of the intervention effects, which will inform future intervention tailoring to meet the needs of vulnerable subgroups.

Risk factors and health behaviors associated with loneliness among cancer survivors during the COVID-19 pandemic.

Loneliness may exacerbate poor health outcomes particularly among cancer survivors during the COVID-19 pandemic. Little is known about the risk factors of loneliness among cancer survivors. We evaluated the risk factors of loneliness in the context of COVID-19 pandemic-related prevention behaviors and lifestyle/psychosocial factors among cancer survivors. Cancer survivors (n = 1471) seen at Huntsman Cancer Institute completed a survey between August-September 2020 evaluating health behaviors, medical care, and psychosocial factors including loneliness during COVID-19 pandemic. Participants were classified into two groups: 'lonely' (sometimes, usually, or always felt lonely in past month) and 'non-lonely' (never or rarely felt lonely in past month). 33% of cancer survivors reported feeling lonely in the past month. Multivariable logistic regression showed female sex, not living with a spouse/partner, poor health status, COVID-19 pandemic-associated lifestyle factors including increased alcohol consumption and marijuana/CBD oil use, and psychosocial stressors such as disruptions in daily life, less social interaction, and higher perceived stress and financial stress were associated with feeling lonely as compared to being non-lonely (all p < 0.05). A significant proportion of participants reported loneliness, which is a serious health risk among vulnerable populations, particularly cancer survivors. Modifiable risk factors such as unhealthy lifestyle behaviors and psychosocial stress were associated with loneliness. These results highlight the need to screen for unhealthy lifestyle factors and psychosocial stressors to identify cancer survivors at increased risk of loneliness and to develop effective management strategies.

Prognostic gene expression profile testing to inform use of adjuvant therapy: A survey of melanoma experts.

OBJECTIVES: To investigate current practices and attitudes regarding use of adjuvant immunotherapy and prognostic gene expression profile (GEP) testing among melanoma medical and surgical oncologists. METHODS: An anonymous RedCap-based survey was emailed to ~300 melanoma experts. RESULTS: Respondents generally favored adjuvant immunotherapy over observation (73% for all Stage IIIA, 50% for Stage IIB/IIC) and cited a minimum 10-year recurrence risk of 11%-20% (48%) or 21%-30% (33%) to justify treatment, but acknowledged that risks of serious adverse events may outweigh potential benefits for some Stage IIB/IIC patients. While GEP test results did not strongly influence decision-making regarding follow-up or intervention, most were receptive to randomized trials using GEP testing to identify subsets of Stage IIB/IIC (74%) and Stage IB/IIA (54%) patients who may not or may, respectively, benefit from adjuvant therapy. CONCLUSION: Although most respondents do not routinely use GEP testing, many would participate in clinical trials to determine clinical utility.

The Family Lifestyles, Actions and Risk Education (FLARE) study: Protocol for a randomized controlled trial of a sun protection intervention for children of melanoma survivors.

BACKGROUND: Children of parents who had melanoma are more likely to develop skin cancer themselves owing to shared familial risks. The prevention of sunburns and promotion of sun-protective behaviors are essential to control cancer among these children. The Family Lifestyles, Actions and Risk Education (FLARE) intervention will be delivered as part of a randomized controlled trial to support parent-child collaboration to improve sun safety outcomes among children of melanoma survivors. METHODS: FLARE is a two-arm randomized controlled trial design that will recruit dyads comprised of a parent who is a melanoma survivor and their child (aged 8-17 years). Dyads will be randomized to receive FLARE or standard skin cancer prevention education, which both entail 3 telehealth sessions with an interventionist. FLARE is guided by Social-Cognitive and Protection Motivation theories to target child sun protection behaviors through parent and child perceived risk for melanoma, problem-solving skills, and development of a family skin protection action plan to promote positive modeling of sun protection behaviors. At multiple assessments through one-year post-baseline, parents and children complete surveys to assess frequency of reported child sunburns, child sun protection behaviors and melanin-induced surface skin color change, and potential mediators of intervention effects (e.g., parent-child modeling). CONCLUSION: The FLARE trial addresses the need for melanoma preventive interventions for children with familial risk for the disease. If efficacious, FLARE could help to mitigate familial risk for melanoma among these children by teaching practices which, if enacted, decrease sunburn occurrence and improve children's use of well-established sun protection strategies.

Electrical Impedance Dermography Differentiates Squamous Cell Carcinoma In Situ from Inflamed Seborrheic Keratoses.

There are no currently available low-cost, noninvasive methods for discerning the depth of squamous cell carcinoma (SCC) invasion or distinguishing SCC from its benign mimics, such as inflamed seborrheic keratosis (SK). We studied 35 subjects with subsequently confirmed SCC or SK. Subjects underwent electrical impedance dermography measurements at six frequencies to assess the electrical properties of the lesion. Averaged greatest intrasession reproducibility values were 0.630 for invasive SCC at 128 kHz, 0.444 for SCC in situ at 16 kHz, and 0.460 for SK at 128 kHz. Electrical impedance dermography modeling revealed significant differences between SCC and inflamed SK in normal skin (P < 0.001) and also between invasive SCC and SCC in situ (P < 0.001), invasive SCC and inflamed SK (P < 0.001), and SCC in situ and inflamed SK (P < 0.001). A diagnostic algorithm classified SCC in situ from inflamed SK with an accuracy of 0.958, a sensitivity of 94.6%, and a specificity of 96.9%; it also classified SCC in situ from normal skin with an accuracy of 0.796, a sensitivity of 90.2%, and a specificity of 51.2%. This study provides preliminary data and a methodology that can be used in future studies to further advance the value of electrical impedance dermography and inform biopsy decision making in patients with lesions suspicious of SCC.

Objectively-Assessed Ultraviolet Radiation Exposure and Sunburn Occurrence.

Ultraviolet radiation (UVR) exposure is the primary modifiable risk factor for melanoma. Wearable UVR sensors provide a means of quantifying UVR exposure objectively and with a lower burden than self-report measures used in most research. The purpose of this study was to evaluate the relationship between detected UVR exposure and reported sunburn occurrence. In this study, a UVR monitoring device was worn by 97 parent-child dyads during waking hours for 14 days to measure instantaneous and accumulated UVR exposure. The results showed that the participants' total UVR exposure was associated with reported sunburn after adjusting for Fitzpatrick skin type and geographic location. It was observed that one standard erythemal dose (SED) increase in the participants' daily total UVR exposure was associated with reported sunburn (an odds ratio (OR) of 1.26 with a 95% CI of 1.13 and 1.41, and p < 0.001 for parents and an OR of 1.28 with a 95% CI of 1.12 and 1.47, and p < 0.001 for children). A one-SED increase in the participants' UVR exposure from 10 am to 4 pm was also associated with reported sunburn (an OR of 1.31 with a 95% CI of 1.15 and 1.49, and p < 0.001 for parents and an OR of 1.33 with a 95% CI of 1.12 and 1.59, and p = 0.001 for children). We found that elevated UVR exposure recordings measured by the UVR sensor were associated with reported sunburn occurrence. Future directions for wearable UVR sensors may include their use as an intervention tool to support in-the-moment sunburn prevention.

Early Detection and Prognostic Assessment of Cutaneous Melanoma: Consensus on Optimal Practice and the Role of Gene Expression Profile Testing.

Importance: Therapy for advanced melanoma has transformed during the past decade, but early detection and prognostic assessment of cutaneous melanoma (CM) remain paramount goals. Best practices for screening and use of pigmented lesion evaluation tools and gene expression profile (GEP) testing in CM remain to be defined. Objective: To provide consensus recommendations on optimal screening practices and prebiopsy diagnostic, postbiopsy diagnostic, and prognostic assessment of CM. Evidence Review: Case scenarios were interrogated using a modified Delphi consensus method. Melanoma panelists (n = 60) were invited to vote on hypothetical scenarios via an emailed survey (n = 42), which was followed by a consensus conference (n = 51) that reviewed the literature and the rationale for survey answers. Panelists participated in a follow-up survey for final recommendations on the scenarios (n = 45). Findings: The panelists reached consensus (≥70% agreement) in supporting a risk-stratified approach to melanoma screening in clinical settings and public screening events, screening personnel recommendations (self/partner, primary care provider, general dermatologist, and pigmented lesion expert), screening intervals, and acceptable appointment wait times. Participants also reached consensus that visual and dermoscopic examination are sufficient for evaluation and follow-up of melanocytic skin lesions deemed innocuous. The panelists reached consensus on interpreting reflectance confocal microscopy and some but not all results from epidermal tape stripping, but they did not reach consensus on use of certain pigmented lesion evaluation tools, such as electrical impedance spectroscopy. Regarding GEP scores, the panelists reached consensus that a low-risk prognostic GEP score should not outweigh concerning histologic features when selecting patients to undergo sentinel lymph node biopsy but did not reach consensus on imaging recommendations in the setting of a high-risk prognostic GEP score and low-risk histology and/or negative nodal status. Conclusions and Relevance: For this consensus statement, panelists reached consensus on aspects of a risk-stratified approach to melanoma screening and follow-up as well as use of visual examination and dermoscopy. These findings support a practical approach to diagnosing and evaluating CM. Panelists did not reach consensus on a clearly defined role for GEP testing in clinical decision-making, citing the need for additional studies to establish the clinical use of existing GEP assays.

Melanoma in skin of color: Part II. Racial disparities, role of UV, and interventions for earlier detection.

Despite a higher incidence of melanoma among White individuals, melanoma-specific survival is worse among individuals with skin of color. Racial disparities in survival are multifactorial. Decreased skin cancer education focused on people with skin of color, lower rates of screening, increased socioeconomic barriers, higher proportions of more aggressive subtypes, and underrepresentation in research and professional education contribute to delays in diagnosis and treatment. Although high, intermittent UV exposure during childhood has been established as a significant modifiable risk factor for melanoma in individuals with lighter skin phototypes, there are limited data on UV exposure and melanoma risk in people with darker skin phototypes. The second article of this continuing medical education series will examine factors contributing to racial disparities in melanoma-specific survival, discuss the role of UV radiation, and address the need for further research and targeted educational interventions for melanoma in individuals with skin of color.

Melanoma in skin of color: Part I. Epidemiology and clinical presentation.

Although there is a higher incidence of melanoma among non-Hispanic White individuals, melanoma is diagnosed at more advanced stages and associated with worse survival rates among individuals with skin of color (SOC). The proportions of melanoma subtypes differ across racial groups, with acral lentiginous melanoma and mucosal melanoma representing higher proportions of melanoma diagnoses in individuals with SOC compared to White individuals. The recognition of distinct differences in anatomic locations and dermatoscopic patterns may facilitate the appropriate differentiation of physiologic from pathologic pigmentation. The first article of this continuing medical education series will focus on the epidemiology and clinical presentation of melanoma in individuals with SOC, with the aim of improving early diagnoses and clinical outcomes.

Cell-intrinsic melanin fails to protect melanocytes from ultraviolet-mutagenesis in the absence of epidermal melanin.

Melanin is a free-radical scavenger, antioxidant, and broadband absorber of ultraviolet (UV) radiation which protects the skin from environmental carcinogenesis. However, melanin synthesis and UV-induced reactive melanin species are also implicated in melanocyte genotoxicity. Here, we attempted to reconcile these disparate functions of melanin using a UVB-sensitive, NRAS-mutant mouse model, TpN. We crossed TpN mice heterozygous for an inactivating mutation in Tyrosinase to produce albino and black littermates on a C57BL/6J background. These animals were then exposed to a single UVB dose on postnatal day three when keratinocytes in the skin have yet to be melanized. Approximately one-third (35%) of black mice were protected from UVB-accelerated tumor formation. However, melanoma growth rates, tumor mutational burdens, and gene expression profiles were similar in melanomas from black and albino mice. Skin from albino mice contained more cyclobutane pyrimidine dimer (CPD) positive cells than black mice 1-h post-irradiation. However, this trend gradually reversed over time with CPDs becoming more prominent in black than albino melanocytes at 48 h. These results show that in the absence of epidermal pigmentation, melanocytic melanin limits the tumorigenic effects of acute UV exposure but fails to protect melanocytes from UVB-induced mutagenesis.

Developing skin cancer education materials for darker skin populations: crowdsourced design, message targeting, and acral lentiginous melanoma.

Despite decreased susceptibility, darker skin individuals who develop melanoma have worse survival. This disparity in melanoma mortality is the largest for any cancer, and partly driven by a lack of patient education materials targeted to darker skin populations in whom acral lentiginous melanoma (ALM) is the most common subtype. To address this communication disparity, the current study reports a multi-phase design process that leverages crowdsourcing and message testing to develop ALM-focused patient education materials for darker skin populations. Crowdsourced design was utilized to develop a pool of designs (phase 1), the pool was narrowed and thematically analyzed (phase 2), and select designs were evaluated via a message experiment (N = 1877). For darker skin populations, designs that depicted people enhanced knowledge of ALM through message memorability. The current study engages melanoma disparities by providing ALM patient education materials for darker skin populations vetted via a multi-phase process.

A Single-Institution Cohort Study With Nevi of Special Site: Recurrence, Progression to Melanoma, and Patterns of Management.

ABSTRACT: Nevi of specialized sites (NOSS) occur on the scalp, ears, flexural, acral, and genital areas and display atypical clinical and histologic features. We assessed NOSS recurrence and progression to melanoma, management patterns, and associations between histologic features and treatment recommendations. We queried all histologic diagnoses of NOSS (n = 275) from 2012 to 2017 from a large U.S. academic medical center with reference dermatopathology laboratory and matched these to clinical records. A blinded panel of dermatopathologists re-evaluated lesions, catalogued histologic findings, and gave management recommendation. Associations with dermatopathologist decision and concordance between new and original recommendations were assessed. Of 117 cases with follow-up, 2 locally recurred (1.46%) and none eventuated in melanoma. Clinical features were not associated with original treatment recommendations. After histopathologic review, large melanocytes [odds ratio ratio (ORR) = 8.00, 95% CI, 1.35-47.4] and junctional mitotic figures (ORR = 65.0, 6.5-650) predicted excision recommendation. Likewise, accumulation of many (>9) high-risk features was associated with excision recommendation. Panel review changed treatment recommendation in 27% of cases. Fair concordance existed between original and panel recommendations (κ = 0.29, 0.15-0.44). The low rate of recurrence and lack of melanoma occurrence suggest that despite an atypical clinical and histopathologic appearance, these nevi have limited potential for malignant transformation. Histopathologic findings seem to be principal drivers behind the recommendation for excision in this analysis. Variability existed in treatment recommendations; the panel's consensus recommendation tended to downgrade treatment. This highlights the importance of further outcomes-based studies to identify true high-risk features and refine management guidelines.

Increasing Skin Cancer Prevention in Young Adults: the Cumulative Impact of Personalized UV Photography and MC1R Genetic Testing.

Skin cancer has become increasingly common among young adults; however, this population does not consistently adhere to recommended methods for preventing the disease. Interventions in college settings have relied on appearance-focused appeals and have not been able to examine the cumulative effect of multiple behavior change and skin cancer risk communication strategies. The goal of the current study was to examine the unique and combined impacts of personalized ultraviolet (UV) radiation photographs, genetic testing for skin cancer risk, and general skin cancer prevention education. Participants were randomly assigned to one of four conditions: (1) skin cancer prevention education, (2) education + UV photo, (3) education + genetic testing, and (4) education + UV photo + genetic testing. Self-reported sun protection, tanning, and sunburn were assessed at baseline, immediately post-intervention, and 1 month post-intervention. The findings indicated benefits of the interventions to skin cancer prevention behaviors in the overall sample; however, the combined (UV photo + genetic testing) intervention had the most consistent positive effects on behaviors. Intervention effects were distinct across seasons. These results suggest that interventions containing multiple skin cancer risk communication strategies hold promise in benefitting health-promoting behavior changes in an at-risk, young adult population.Trial Registration Number: NCT03979872; Registered 6/5/2019.

Tailored visuals, implementation interventions, and sun safe behavior: A longitudinal message experiment.

OBJECTIVE: One way to communicate skin cancer risk is through ultraviolet (UV) photographs, which can depict the target person (tailored visual) or someone else (stock visual). There is a need for more longitudinal research examining the relative impact of tailored UV photographs compared with other message interventions that could increase sun safe behaviors. METHOD: Students 14-18 years of age (N = 654) at eleven high schools in Utah were recruited to participate in a longitudinal experiment (assessments: pretest, posttest, 1 month follow-up) comparing the relative persuasive impact of receiving either (a) stock and tailored UV photographs or (b) stock UV photographs and an implementation intervention on outdoor tanning behavior. Participants completed measures of fear, appearance norms and benefits, threat susceptibility/severity, self-efficacy, response efficacy, freedom threat, reactance, and outdoor tanning behavior. RESULTS: Compared with the implementation intervention, participants in the tailored UV condition reported increased fear and freedom threat and decreased appearance norms and benefits of tanning immediately following exposure to the intervention and decreased outdoor tanning 1 month after the intervention. Indirect effects also emerged with tailored UV exposure decreasing outdoor tanning via appearance benefits and increasing outdoor tanning when immediate fear triggered psychological reactance. CONCLUSIONS: The results contribute to research on lay reactions to tailored visuals, implementation interventions, and theorizing the indirect effects of affect and cognition across time. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Aspirin Protects against UVB-Induced DNA Damage through Activation of AMP Kinase.

The anti-inflammatory and chemopreventive activities of aspirin (ASA) may be mediated through its cyclooxygenase inhibitor function. We have previously shown that ASA can protect against UVR-induced skin inflammation and DNA damage; however, the role of inflammation in UV-induced DNA damage and the mechanism underlying ASA protection are poorly characterized. Using immunodeficient NOD scid gamma mice and immunocompetent C57BL/6 mice treated with immune cell‒depleting antibodies, we found that inflammation was not required for UVB-induced 8-oxoguanine and cyclobutane pyrimidine dimers in vivo. Unlike ASA, neither its immediate metabolite salicylate nor the cyclooxygenase inhibitor indomethacin reduced UVB-induced 8-oxoguanine or cyclobutane pyrimidine dimers in melanocyte Melan-a or keratinocyte HaCat cells in vitro. Moreover, addition of prostaglandin E2 did not reverse the protective effect of ASA on UVB-treated cells. Phosphorylation of the 5' AMP protein kinase, observed in ASA-treated cells, could be blocked by the 5' AMP protein kinase inhibitor compound C. Compound C or 5' AMP protein kinase knockdown partially reduced ASA-mediated protection against UVB-induced DNA damage. Finally, injection of compound C partially reversed the protective effect of ASA on UVB-treated mouse skin in vivo. These studies suggest that ASA confers protection against UVB-induced DNA damage through the activation of 5' AMP protein kinase rather than through cyclooxygenase inhibition.

'I had a bigger cancer risk than I thought ': The experience of receiving personalized risk information as part of a skin cancer prevention intervention in the college setting.

BACKGROUND: Diagnoses of both melanoma and nonmelanoma skin cancers are becoming increasingly common among young adults. Interventions in this population are a priority because they do not consistently follow skin cancer prevention recommendations. OBJECTIVES: The goal of the current study was to examine college students' perspectives on and experience with receiving a skin cancer prevention intervention that provided personalized skin cancer risk feedback in the form of an ultraviolet (UV) photograph, the results of genetic testing for common skin cancer risk variants, and/or general skin cancer prevention education. METHODS: Qualitative interviews were conducted with 38 college students who received a skin cancer prevention intervention. The interview covered students' feelings about their personal skin cancer risk information, the impact of the intervention on their skin cancer risk perceptions, actions or intentions to act with regard to their sun protection practices and feedback for improvement of the intervention content or delivery. RESULTS: Participants reported that different intervention components contributed to increased awareness of their sun protection behaviours, shifts in cognitions about and motivation to implement sun protection strategies and reported changes to their skin cancer prevention strategies. CONCLUSION: Our findings indicate that college students are interested in and responsive to these types of multicomponent skin cancer preventive interventions. Further, students demonstrate some motivation and intentionality toward changing their skin cancer risk behaviour in the short term. PATIENT OR PUBLIC CONTRIBUTION: Participants involved in this study were members of the public (undergraduate students) who were involved in a skin cancer prevention intervention, then participated in semistructured interviews, which provided the data analysed for this study.