Spectrum of malignant and premalignant skin lesions in 505 adult subjects at risk of skin cancers.

Patients at risk of skin cancers can develop varying types of cutaneous malignancies. However, some subjects may develop only one type of lesion. In this cross-sectional study, the spectrum of premalignant (PM) and malignant skin lesions and their risk factors were studied. Therefore, 505 adult subjects (aged 21-79 years, 256 males and 249 females, 96 with immunosuppression) at risk of any type of skin cancer were examined for cutaneous malignancies, nevi, actinic keratoses, photodamage, and possible risk factors. First, 12 different groups were identified with a varying set of PM and/or malignant skin lesions. Next, 5 larger groups were formed from them: basal cell carcinoma (BCC) only, malignant melanoma (MM) only, squamous cell carcinoma (SCC) and/or PM, BCC + SCC and/or PM, and MM + keratinocyte carcinoma (KC) and/or PM. The groups with BCC or MM only were younger and showed less photodamage than the mixed groups, while SCC/PM showed similarity with them. In logistic regression analyses, the platelet-to-lymphocyte ratio was associated with an increased risk of concomitant KC (OR 1.028, p = 0.023) or SCC/PM (OR 1.009, p = 0.047) in subjects with MM or BCC, respectively. Actinic keratoses produced ORs 0.246-0.252 (p = 0.008-0.020) for BCC in subjects with SCC/PM. Interestingly, atypical mole syndrome decreased the risk of SCC/PM in subjects with BCC (OR 0.092, p = 0.001). Advanced age was a significant risk factor for an additional type of lesion in all 3 comparisons (ORs 1.088-1.388, p = 0.001). In conclusion, even though there are numerous patients with only one lesion type, advancing age may determine the final lesion multiplicity.

Shedding new light on actinic keratoses and squamous cell carcinoma in situ.

ABSTRACT: Cutaneous squamous cell carcinoma can arise from various premalignant lesions such as actinic keratosis, Bowen disease, and premalignant genital squamous cell lesions. Identification and treatment can prevent malignant transformation and death. This article describes the causes, epidemiology, and characteristics of suspicious premalignant squamous cell lesions so that clinicians can identify these lesions and refer patients for specialist treatment as appropriate.

Epidemiology and risk factors for multiple squamous cell carcinomas in a cohort of organ transplant recipients from northern Italy: a single center study.

BACKGROUND: Keratinocyte cancers account for the most frequent oncological complication in organ transplant recipients. To date, many different risk factors have been reported, unless variability among the studies exist. We aimed to determine the incidence and risk factors for keratinocyte neoplasms in a cohort of kidney transplant and liver transplant recipients. METHODS: A cohort of 338 patients were included in this retrospective study and followed-up from transplantation until the end of December 2021, with a 2-year minimum transplant time. Each skin cancer was collected in a specific database, together with all the demographic data and dermatological history and feature of patients. RESULTS: In our cohort, liver transplant patients presented a higher keratinocyte cancer incidence compared to kidney transplant recipients. Regarding the risk factors for skin cancer in the entire group of patients, we observed a significant association with the detection of actinic keratosis and solar lentigo, and such relation was stronger when considering patients developing multiple skin cancers, in which fair skin types and occupational sun exposure were also associated. Furthermore, while actinic keratosis and a history of previous dialysis were significantly associated with the development of a least one squamous cell carcinoma, the presence of keratotic lesions and azathioprine intake resulted connected with the appearance of multiple squamous neoplasms. CONCLUSIONS: We report here that, in our cohort, factors potentially leading to immune dysfunction were found to play a causative role in the development of the more aggressive histotype of keratinocyte tumors, and such association seemed more convincing in case of multiple squamous cell carcinomas.

Skin Cancers in Medicare Beneficiaries With Actinic Keratoses.

Importance: Actinic keratoses (AK) are common premalignant skin lesions with a small risk of progressing to cutaneous squamous cell carcinoma (SCC). There is some evidence that patients with AKs also have increased risks of other skin cancers beyond SCC. However, the absolute risks of skin cancer in patients with AKs are unknown. Objective: To calculate the absolute and relative risks of future skin cancer in Medicare beneficiaries with AKs. Design, Setting, and Participants: This retrospective cohort study was performed using a deidentified, random sample of 4 999 999 fee-for-service Medicare beneficiaries from 2009 through 2018. Patients with treated AKs were included, and patients with seborrheic keratoses (SKs) were included as a comparator group. All patients were required to have at least 1 year between data set entry and first AK or SK. Patients with a history of skin cancer were excluded. Data were analyzed from September 2022 to March 2023. Main Outcomes and Measures: Outcomes were first surgically treated skin cancer, including keratinocyte carcinoma (including SCC and basal cell carcinoma [BCC]) and melanoma. The absolute risks of skin cancer in patients with AKs were evaluated. Skin cancer risks in patients with AKs were compared with patients with SKs using adjusted competing risks regression. Results: A total of 555 945 patients with AKs (mean [SD] age, 74.0 [7.4] years; 55.4% female) and 481 024 patients with SKs (mean [SD] age, 73.3 [7.3] years; 72.4% female) were included. The absolute risk of skin cancer after a first AK was 6.3% (95% CI, 6.3%-6.4%) at 1 year, 18.4% (95% CI, 18.3%-18.5%) at 3 years, and 28.5% (95% CI, 28.4%-28.7%) at 5 years. Patients with AKs had increased risk of skin cancer compared with patients with SKs (any skin cancer: adjusted hazard ratio [aHR], 2.17; 95% CI, 2.15-2.19; keratinocyte carcinoma: aHR, 2.20; 95% CI, 2.18-2.22; SCC: aHR, 2.63; 95% CI, 2.59-2.66; BCC: aHR, 1.85; 95% CI, 1.82-1.87; and melanoma: aHR, 1.67; 95% CI, 1.60-1.73). Conclusions and Relevance: In this cohort study, older patients with AKs had substantial absolute risks, as well as elevated relative risks, of skin cancer. AKs may be clinical markers of UV exposure and increased skin cancer risk, including SCC, BCC, and melanoma. However, guidelines are lacking for follow-up skin cancer surveillance in patients with AKs. Efforts to develop evidence-based recommendations for skin cancer surveillance in patients with AKs are paramount.

S3 guideline "actinic keratosis and cutaneous squamous cell carcinoma" - update 2023, part 2: epidemiology and etiology, diagnostics, surgical and systemic treatment of cutaneous squamous cell carcinoma (cSCC), surveillance and prevention.

Actinic keratosis (AK) are common lesions in light-skinned individuals that can potentially progress to cutaneous squamous cell carcinoma (cSCC). Both conditions may be associated with significant morbidity and constitute a major disease burden, especially among the elderly. To establish an evidence-based framework for clinical decision making, the guideline "actinic keratosis and cutaneous squamous cell carcinoma" was updated and expanded by the topics cutaneous squamous cell carcinoma in situ (Bowen's disease) and actinic cheilitis. The guideline is aimed at dermatologists, general practitioners, ear nose and throat specialists, surgeons, oncologists, radiologists and radiation oncologists in hospitals and office-based settings, as well as other medical specialties, policy makers and insurance funds involved in the diagnosis and treatment of patients with AK and cSCC. A separate guideline exists for patients and their relatives. In this part, we will address aspects relating to epidemiology and etiology, diagnostics, surgical and systemic treatment of cutaneous squamous cell carcinoma (cSCC), surveillance and prevention.

An epidemiological study on skin tumors of the elderly in a community in Shanghai, China.

The morbidity of skin tumors (ST) in China is a great concern as the population ages. No epidemiological survey on ST in elderly communities in China has been reported. A questionnaire survey was conducted among the residents over 60 years old in a community in Shanghai, China from May 1, 2011 to November 30, 2011. The prevalence of cutaneous tumors and associated factors were analyzed. Among 2038 valid cases, a total of 78 (3.8%, 95% CI 3.0-4.7) skin cancers (SC) were confirmed. According to the final multivariate regression analysis, age, gender and previous occupation were the significantly influential factors for SC. Actinic keratosis (AK) accounted for the largest proportion (63, 3.1%) in SC. The head and neck was the physiological site with the highest incidence of SC (64, 82.1%), and AK was the most common (55, 87.3%) in head and neck SC. The common concomitant diseases of SC were hypertension (26, 33.3%) and diabetes mellitus (9, 11.5%). Seborrheic keratosis (SK) was the most common benign skin tumor with a prevalence of 100%. Men and women developed SK in significantly different parts of the body (P < 0.0001). The incidence of ST in the elderly population in Shanghai community increased with age. ST preferred to occur in the head and neck, which might be attributed to excessive ultraviolet (UV) exposure in these areas. Therefore, early diagnosis and sun-protection education are essential interventions for ST in the elderly.

Skin Cancer Development Is Strongly Associated with Actinic Keratosis in Solid Organ Transplant Recipients: A Danish Cohort Study.

BACKGROUND AND OBJECTIVES: Solid organ transplant recipients (SOTRs) are at increased risk of skin cancer and suffer from greater disease-specific morbidity and mortality. To risk stratify the expanding SOTR population for more targeted skin cancer screening, a detailed understanding of risk factors is needed. Using combined clinical and pathological data to capture prevalence of actinic keratosis (AK) and skin cancer, this study aimed to identify risk factors of skin cancer development in a Danish SOTR cohort. METHODS: The trial comprised a retrospective cohort study of patients attending organ transplant clinics at the dermatological departments of Bispebjerg and Gentofte Hospitals in Copenhagen, Denmark, between 2009 and 2021. In addition to pathology records, AK prevalence was determined by review of electronic medical records (EMRs) of SOTR visits which specifically included descriptions of clinical AK. Prevalence of skin cancer, here defined as basal cell carcinoma (BCC), squamous cell carcinoma (SCC) (invasive or in situ), or melanoma (invasive or in situ), was determined by EMR and pathology code review. Additional data extracted from EMRs included age, sex, Fitzpatrick skin type, transplantation date and type, and immunosuppressive therapy. The effect of risk factors on skin cancer was calculated by Cox proportional hazards regression. RESULTS: A total of 822 SOTRs were included with a mean follow-up duration of 10.8 years (SD 2.4 years). A skin dysplasia diagnosis was identified in 30% (n = 250) of the population, consisting of either AK (22%; n = 177), skin cancer (23%; n = 186) or both (14%; n = 113). An AK diagnosis predicted both SCC (odds ratio [OR]: 31.5 [95% CI: 9.8-100.6], p < 0.0001) and BCC development (OR: 2.3 [95% CI: 1.6-3.3], p < 0.0001), with AKs diagnosed an average 3.1 years before the first SCC (p < 0.0001). Correspondingly, while the risk of SCC in SOTRs without AK was 1.4% 25 years after transplantation, SOTRs with AKs had a 23% SCC risk only 10 years posttransplant. Other identified risk factors included Fitzpatrick skin type I (BCC: OR: 2.4 [95% CI: 1.2-5.0], p = 0.018; SCC: 3.2 [95% CI: 1.2-8.2], p = 0.016) and transplantation duration >15 years (BCC: OR: 1.8 [95% CI: 1.2-2.7], p = 0.007). No significant association between skin cancer development and sex or immunosuppressive regimen was shown. CONCLUSION: Keratinocyte carcinoma is strongly associated with an AK diagnosis in SOTRS and should prompt intensified skin cancer screening in affected individuals.

Significant Association of Poly-A and Fok1 Polymorphic Alleles of the Vitamin D Receptor with Vitamin D Serum Levels and Incidence of Squamous Cutaneous Neoplasia.

Vitamin D3, a prohormone, is converted to circulating calcidiol and then to calcitriol, the hormone that binds to the vitamin D receptor (VDR) (a nuclear transcription factor). Polymorphic genetic sequence variants of the VDR are associated with an increased risk of breast cancer and melanoma. However, the relationship between VDR allelic variants and the risk of squamous cell carcinoma and actinic keratosis remains unclear. We examined the associations between two VDR polymorphic sites, Fok1 and Poly-A, and serum calcidiol levels, actinic keratosis lesion incidence, and the history of cutaneous squamous cell carcinoma in 137 serially enrolled patients. By evaluating the Fok1 (F) and (f) alleles and the Poly-A long (L) and short (S) alleles together, a strong association between genotypes FFSS or FfSS and high calcidiol serum levels (50.0 ng/ml) was found; conversely, ffLL patients showed very low calcidiol levels (29.1 ng/ml). Interestingly, the FFSS and FfSS genotypes were also associated with reduced actinic keratosis incidence. For Poly-A, additive modeling showed that Poly-A (L) is a risk allele for squamous cell carcinoma, with an OR of 1.55 per copy of the L allele. We conclude that actinic keratosis and squamous cell carcinoma should be added to the list of squamous neoplasias that are differentially regulated by the VDR Poly-A allele.

Oral nicotinamide for non-melanoma skin cancers: A review.

There has been much interest in the role of oral nicotinamide supplementation in reducing the incidence of non-melanoma skin cancers. This article reviews the hypothesised mechanisms of action of nicotinamide, and the available literature outlining its role for this purpose. There have been five randomised controlled trials (RCT), one histopathological study and two case series exploring the effect of oral nicotinamide supplementation on UV-induced immunosuppression of the skin, and incidence of actinic keratoses and non-melanoma skin cancers (NMSC). The largest RCT received criticism of the statistical analyses used, but the critics still acknowledged a likely benefit of treatment with oral nicotinamide in reducing the incidence of NMSC. Nicotinamide has a favourable safety profile. Current evidence is not definitive that oral nicotinamide supplementation reduces the incidence of NMSC, but it constitutes a low-risk management option that may be particularly relevant for high-risk individuals, and should be discussed as an option for these patients.

Risk of Skin Cancer and Actinic Keratosis in Patients with Rosacea: A Nationwide Population-based Cohort Study.

The association between rosacea and skin cancer remains inconclusive, with conflicting reports. The aim of this nationwide population-based cohort study was to determine the risk of skin cancer in patients with rosacea. A rosacea cohort (n = 11,420) was formulated and evaluated from 2010 to 2019. The incidence rate ratios of actinic keratosis, cutaneous melanoma, keratinocyte carcinoma and gastric, colorectal, and liver cancer were analysed in comparison with a matched control group, and multivariable stratified Cox proportional hazards model analysis was performed. The risk of actinic keratosis and keratinocyte carcinoma was increased in the rosacea group compared with the control group, with adjusted hazard ratios of 6.05 (95% confidence interval 3.63-10.09) and 2.66 (1.53-4.61), respectively. The risk of cutaneous melanoma and gastric, colorectal and liver cancer was not increased, with adjusted hazard ratios of 1.69 (0.25-11.37), 0.81 (0.59-1.10), 0.91 (0.69-1.18) and 1.32 (0.89-1.95), respectively. These results reveal an increased risk of actinic keratosis and keratinocyte carcinoma in patients with rosacea.

Correlation of skin cancer and actinic keratosis-related knowledge and sun protection behaviors and sunscreen use among a sample of Jordanian population.

BACKGROUND: The incidence of skin cancer and actinic keratosis has increased worldwide. Measuring the public awareness, attitude, and knowledge about these diseases and the skin protection behaviors are highly important to undertake preventive measures. METHODS: To investigate skin cancer and actinic keratosis-related knowledge, sun protection behaviors, and sunscreen usage among Jordanians, a questionnaire was developed. The questionnaire was provided as a google form to individuals via social media and the data were analyzed using SPSS® 23. RESULTS: A total of 1277 individuals, aged 18-65 years filled the questionnaire. The median melanoma and actinic keratosis knowledge score were 7 (4-9) and 4 (0-9), respectively. The melanoma knowledge was higher among females, those with a medical background, a high level of education, and in the central region, whereas the AK knowledge was higher among those with a medical background. Overall, 75.9% of the participants used sunscreen at least often to prevent sunburn, uneven skin tone, or tanning, 72% were using sunscreen with an SPF of 30 at least. However, 45.3% and 49.2% of sunscreen users did not comply with application, and reapplication times, respectively. Moreover, 58.4% of participants applied less than the recommended amount of sunscreen. CONCLUSION: Our study revealed that public awareness of actinic keratosis is low among Jordanians. Although it was found that a high proportion of Jordanians use sunscreens there are deficits in sunscreen practice indicating an urgent need to design effective interventions to increase awareness of actinic keratosis and correct use of sunscreen via health campaigns or healthcare professions.

Validation of actinic keratosis diagnosis and treatment codes among veterans living with HIV.

PURPOSE: Actinic keratoses (AK) diagnosis, billing, and pharmacy codes have not been validated among people living with human immunodeficiency virus (HIV), preventing use in epidemiologic and clinical research. We aimed to calculate the positive predictive value (PPV) of AK diagnosis codes, procedural codes for destruction of pre-malignant lesions, and pharmacy codes for topical 5-fluorouracil. METHODS: Patients diagnosed with HIV within the Infectious Disease clinic at the Atlanta Veterans Affairs Medical Center from 1/1/2002 to 8/5/2017 were eligible. Patients were included if they had any of the following: encounters with a diagnosis for AK (International Classification of Diseases [ICD]-9: 702.0; ICD-10: L57.0), procedural codes for destruction of premalignant lesions (Current Procedural Terminology [CPT]: 17000, 17003, and 17004), and prescriptions for topical 5-fluorouracil. PPV and binomial 95% confidence intervals were calculated. RESULTS: PPV was 91.9% (89.1-94.7) for 369 encounters with an AK diagnosis. For procedural codes, PPV was 52.6% (48.1-57.2) for 454 encounters with destruction of 1 pre-malignant lesion, 63.7% (58.4-68.9) for 322 encounters with destruction of 2-14 lesions, and 57.7% (38.7-76.7) for 26 encounters with destruction of 15+ lesions. PPV was 72.9% (63.5-82.4) for 85 encounters with a prescription of topical 5-fluorouracil. CONCLUSION: AK diagnosis codes are appropriate to use in epidemiologic and health policy research among people living with HIV and may be more reliable than destruction of pre-malignant lesion CPT codes.

Workforce Requirements for Skin Cancer and Related Skin Tumors Continue to Increase: Clinicians Expend an Average of 1,740 Full-Time Effort Years Annually.

BACKGROUND: With an aging population, estimating workforce requirements for management of common conditions such as skin cancer will be necessary to meet the health care needs of the American people. OBJECTIVE: The authors aimed to estimate the workforce requirements for managing skin cancer and other skin tumors. MATERIALS AND METHODS: The authors conducted a population-based, cross-sectional analysis using data from the National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey between the years 2007 and 2016, the most recent years available. The significance threshold was set at a p-value <.05. RESULTS: The full-time effort of 1,740 (95% confidence interval: 1,340-2,220) clinicians is required to care for skin cancer and other skin tumors each year. The full-time effort years necessary for management of melanoma (p = .006), keratinocytic carcinoma (p < .0001), actinic keratosis (p < .0001), and all skin cancers and tumors (p < .0001) were significantly increasing from 2007 to 2016. CONCLUSION: Clinicians expend a significant amount of time managing skin cancer and other skin tumors, and the time required for management increased over the study period. These workforce requirement trends can likely be attributed to increased prevalence and incidence rates of cutaneous malignancy secondary to an aging population and increased whole-body skin examinations.

A multicenter retrospective analysis of the clinical and pathological characteristics of 1188 cases of actinic keratosis in different ultraviolet radiation intensity areas of China.

BACKGROUND: Actinic keratosis (AK) is a precancerous disease, caused by ultraviolet radiation (UV). OBJECTIVE: To analyze the clinical and pathological characteristics of AK in four areas with different ultraviolet radiation intensities. METHODS: 1188 diagnosed AK patients, from January 2000 to July 2015, in dermatology department of four hospitals were collected. The UV intensity of hospital located cities from high to low is Kunming, Yinchuan, Shenyang and Nanjing. The information comes from medical records, and the pathological types and Keratinocyte Intraepithelial Neoplasia (KIN) grades were checked by two experienced pathologists. All information was conducted a retrospective multicenter research. RESULTS: The patients were mainly middle-aged and elderly female, which was in direct contrast to the majority of men in European. The age of onset in Kunming group was lower than that in Yinchuan Group (p = 0.013) and Nanjing Group (p < 0.01). The course of disease in Kunming group was significantly shorter than that in Nanjing Group (p < 0.001). The lesions were almost located in the exposed area. The proportion of unexposed areas in Shenyang group was significantly higher than that in other groups (p < 0.001). There were statistical differences in pathological morphological classification among the four groups. These differences were not affected by age and gender. The number of KIN III grade patients in Shenyang group was significantly higher than that in other three groups (p < 0.05). CONCLUSION: The Asian patients were mainly female. The clinical characteristics of AK are closely related to UV intensity, and environmental pollution, lifestyle, religious beliefs and other factors are also related.

The Preventive Value of Sun Protection.

BACKGROUND: With more than 200,000 new cases per year, skin tumours have been the most frequently reported cancers in Germany for years. We performed a systematic review to summarise the current evidence concerning the preventive value of regular sunscreen use. METHODS: Systematic literature review of controlled and randomised controlled trials were performed in Ovid Embase and Ovid Medline on 21 January 2020. We included studies evaluating the effectiveness of sunscreens on epithelial skin cancer, actinic keratosis or photoageing, or side effects in humans. RESULTS: Five eligible trials, each involving 28 to 1,621 participants from various populations, were identified. All 4 studies on actinic keratoses showed a significant beneficial effect of sunscreens. The 2 studies on squamous cell carcinoma demonstrated significant beneficial effects of sunscreens. The 2 studies on photoageing observed a significant reduction in the sunscreen groups. The 2 studies on basal cell carcinoma reported no significant results, but both studies reported some non-significant protective effects of sunscreen use. Sunscreens as well as vehicles sometimes had side effects affecting skin and eyes. Compared with controls, sunscreens had no significant side effects on vitamin D, bone mass density and mortality. CONCLUSION: The evidence from published controlled and randomised controlled studies is limited. Especially for basal cell carcinoma, further high-quality studies including young populations are required to investigate possible protective effects of modern broad-spectrum sunscreens. The results of this systematic review do not change the current recommendations for UV protection. Sunscreens are recommended as a second-line measure against solar radiation whenever protective clothing and seeking shake are inadequate.

Positive association between actinic keratosis and internal malignancies: a nationwide population-based cohort study.

Little is known about the comorbidities in actinic keratosis patients. To evaluate the association of actinic keratosis with certain malignancies. All patients with actinic keratosis (n = 61,438) and age- and sex-matched control subjects (n = 307,190) at a 5:1 ratio were enrolled using data from the Korean National Health Insurance Service between the years 2007 and 2014. In subjects with actinic keratosis, overall cancer incidence was higher than that for controls after income level, habitat, diabetes, hypertension, and dyslipidemia were adjusted (Hazard Ratio [HR] = 1.43 [95% confidence interval 1.38-1.47]). The positive association of specific cancers were observed in the following order: skin cancer (HR = 3.43 [2.47-4.75]), oral cavity and pharyngeal cancer (HR = 1.99 [1.57-2.52]), lymphoma (HR = 1.59 [1.28-1.96]), leukemia (HR = 1.35 [1.03-1.77]), prostate cancer (HR = 1.35 [1.21-1.51]), renal cancer (HR = 1.29 [1.02-1.63]), liver cancer (HR = 1.21 [1.09-1.35]), thyroid cancer (HR = 1.20 [1.05-1.38]), and gastric cancer (HR = 1.13 [1.03-1.23]). Although further research on pathologic mechanism is needed, the implications of a positive correlation between actinic keratosis and internal organ malignancies has great significance.

Association of Actinic Keratosis with Rheumatoid Arthritis and Psoriasis: A Nationwide Population-Based Study in Korea.

There have been no epidemiological studies identifying associations between systemic inflammatory diseases and actinic keratosis. This study used a large nationwide database to investigate the associations between actinic keratosis and systemic inflammatory diseases. Records of patients over 20 years of age newly diagnosed with actinic keratosis (n = 64,659) from 2012 to 2017 were analysed. A control population of individuals without actinic keratosis, matched for age, sex, and year of claim, who visited an outpatient clinic, was sampled at a ratio of 1:1 (n = 64,659). Both cohorts were analysed for the presence of systemic inflammatory diseases within at least 5 years prior to diagnosis of actinic keratosis. Patients with actinic keratosis exhibited higher odds ratios for rheumatoid arthritis (1.336; 95% confidence interval (95% CI) 1.161-1.537)) and psoriasis (1.513; 95% CI 1.435-1.595) compared with the control group on multivariate analysis. However, the proportions of Behçet's disease, Crohn's disease, ulcerative colitis, and multiple sclerosis in the actinic keratosis group were not statistically significant.