Keratinocyte Carcinoma Research Articles

Antihypertensive Medications and Risk of Melanoma and Keratinocyte Carcinomas: A Systematic Review and Meta-Analysis

Some anti-hypertensive medications are photosensitizing. The implications for skin cancer risk remain unclear, as results from prior studies are inconsistent and as new evidence is published. We performed a systematic review and meta-analysis to evaluate the association between anti-hypertensives and common skin cancers (cutaneous squamous cell carcinoma (SCC), basal cell carcinoma (BCC), and melanoma), and to evaluate dose-response relationships. Forty-four articles met inclusion criteria, and 42 could be meta-analyzed. Increased risks were seen for BCC with calcium channel blockers (relative risk [RR] 1.17, 95% CI 1.11-1.22), diuretics (RR 1.06, 95% CI 1.03-1.10), and thiazides (RR 1.10, 95% CI 1.04-1.16); for SCC with calcium channel blockers (RR 1.08, 95% CI 1.01-1.14), diuretics (RR 1.29, 95% CI 1.17-1.43), and thiazides (RR 1.36, 95% CI 1.15-1.61); and for melanoma in angiotensin-converting-enzyme inhibitors (RR 1.09, 95% CI 1.03-1.14), calcium channel blockers (RR 1.08, 95% CI 1.03-1.12), and thiazides (RR 1.09, 95% CI 1.02-1.17). The quality of evidence was low or very low. We observed evidence for dose-response for thiazides with BCC, angiotensin-converting-enzyme inhibitors, diuretics, and thiazides with SCC, and angiotensin-converting-enzyme inhibitors, diuretics, and thiazides with melanoma. Our meta-analysis supports a potential causal association between some antihypertensives, particularly diuretics, and skin cancer risk.

Unveiling the Therapeutic Horizon: HPV Vaccines and Their Impact on Cutaneous Diseases-A Comprehensive Review.

Human papillomavirus (HPV) encompasses a diverse array of viruses, comprising approximately 200 serotypes that affect humans. While the majority of HPV strains are associated with benign skin or mucous membrane growths, a subset is implicated in severe health conditions, such as cervical, anal, vulvar, and vaginal cancers. Despite the established effectiveness of HPV vaccines in preventing cervical and anal carcinomas in particular, their therapeutic potential in addressing cutaneous diseases linked to diverse HPV strains remains an intriguing area of investigation. This narrative review critically examines the existing literature to assess the viability of HPV immunization as a therapeutic intervention for prevalent cutaneous conditions. These include genital and extragenital cutaneous warts, epidermodysplasia verruciformis, and keratinocyte carcinomas. The findings suggest a promising dual role for HPV vaccines in preventing and treating dermatologic conditions while emphasizing future research directions, including the immunization perspective against β-HPVs. Moreover, the presence of conflicting study outcomes underscores the imperative for larger-scale, randomized trials with well-matched control groups to validate the efficacy of HPV immunization in the dermatologic context. This review contributes valuable insights into the evolving landscape of HPV-vaccine applications in the field of dermatology.

Association between dermatology follow-up and melanoma survival: A population-based cohort study

BackgroundGuidelines recommend that patients with melanoma undergo dermatologic examination at least annually. Adherence to follow-up and its impact on survival are unclear. ObjectiveTo determine the level of adherence to annual dermatologic follow-up in patients with primary cutaneous melanoma, identify predictors for better adherence, and evaluate whether adherence was associated with melanoma-related mortality. MethodsRetrospective inception cohort analysis of adults with primary invasive melanoma in Ontario, Canada from 2010-2013 with follow-up until December 31, 2018 ResultsAdherence to dermatologic follow-up was variable with only 28.0% of patients seeing a dermatologist at least annually (median follow-up 5.0 years). Younger age, female sex, higher income, greater access to dermatology care, stage 2/3 melanoma, prior keratinocyte carcinoma, fewer comorbidities, and any outpatient visit in the 12 months prior to melanoma diagnosis were predictors for adherence. Greater adherence to annual dermatology visits was associated with reduced melanoma-specific mortality compared with lower levels of adherence (adjusted hazard ratio 0.64, 95% CI 0.52-0.78). LimitationsObservational study design and inability to identify skin examinations performed by non-dermatologists ConclusionAdherence to annual dermatology visits after melanoma diagnosis was low. Greater adherence may promote better patient survival but warrants confirmation in further research including randomized trials.

A Digital Intervention to Improve Skin Self-Examination Among Survivors of Melanoma: Protocol for a Type-1 Hybrid Effectiveness-Implementation Randomized Trial.

Although melanoma survival rates have improved in recent years, survivors remain at risk of recurrence, second primary cancers, and keratinocyte carcinomas. The National Comprehensive Cancer Network recommends skin examinations by a physician every 3 to 12 months. Regular thorough skin self-examinations (SSEs) are recommended for survivors of melanoma to promote the detection of earlier-stage, thinner melanomas, which are associated with improved survival and lower treatment costs. Despite their importance, less than a quarter of survivors of melanoma engage in SSEs. Previously, our team developed and evaluated a web-based, fully automated intervention called mySmartSkin (MSS) that successfully improved SSE among survivors of melanoma. Enhancements were proposed to improve engagement with and outcomes of MSS. The purpose of this paper is to describe the rationale and methodology for a type-1 hybrid effectiveness-implementation randomized trial evaluating the enhanced MSS versus control and exploring implementation outcomes and contextual factors. This study will recruit from state cancer registries and social media 300 individuals diagnosed with cutaneous malignant melanoma between 3 months and 5 years after surgery who are currently cancer free. Participants will be randomly assigned to either enhanced MSS or a noninteractive educational web page. Surveys will be collected from both arms at baseline and at 3, 6, 12, and 18 months to assess measures of intervention engagement, barriers, self-efficacy, habit, and SSE. The primary outcome is thorough SSE. The secondary outcomes are the diagnosis of new or recurrent melanomas and sun protection practices. Multilevel modeling will be used to examine whether there are significant differences in survivor outcomes between MSS and the noninteractive web page over time. Mixed methods will evaluate reach, adoption, implementation (including costs), and potential for maintenance of MSS, as well as contextual factors relevant to those outcomes and future scale-up. This trial has the potential to improve outcomes in survivors of melanoma. If MSS is effective, the results could guide its implementation in oncology care and nonprofit organizations focused on skin cancers. RR1-10.2196/52689.

Oral intake of bucillamine, carvedilol, metformin, or phenformin does not protect against UVR-induced squamous cell carcinomas in hairless mice

Squamous cell carcinoma represents the second most common type of keratinocyte carcinoma with ultraviolet radiation (UVR) making up the primary risk factor. Oral photoprotection aims to reduce incidence rates through oral intake of photoprotective compounds. Recently, drug repurposing has gained traction as an interesting source of chemoprevention. Because of their reported photoprotective properties, we investigated the potential of bucillamine, carvedilol, metformin, and phenformin as photoprotective compounds following oral intake in UVR-exposed hairless mice. Tumour development was observed in all groups in response to UVR, with only the positive control (Nicotinamide) demonstrating a reduction in tumour incidence (23.8%). No change in tumour development was observed in the four repurposed drug groups compared to the UV control group, whereas nicotinamide significantly reduced carcinogenesis (P = 0.00012). Metformin treatment significantly reduced UVR-induced erythema (P = 0.012), bucillamine and phenformin increased dorsal pigmentation (P = 0.0013, and P = 0.0005), but no other photoprotective effect was observed across the repurposed groups. This study demonstrates that oral supplementation with bucillamine, carvedilol, metformin, or phenformin does not affect UVR-induced carcinogenesis in hairless mice.Graphical

Associated Factors of Anxiety Symptoms in Patients with Keratinocyte Carcinoma: A Cross-Sectional Study

Associated Factors of Anxiety Symptoms in Patients with Keratinocyte Carcinoma: A Cross-Sectional Study

A-365 - Measuring health-related quality of life in patients with keratinocyte carcinoma: A multicenter cross-sectional study

A-365 - Measuring health-related quality of life in patients with keratinocyte carcinoma: A multicenter cross-sectional study

A Review of the Dermatologic Clinical Applications of Topical Photodynamic Therapy.

Topical photodynamic therapy is a widely approved therapy for actinic keratoses and low-risk nonmelanoma skin cancers with a rapidly growing range of emerging indications for other cutaneous diseases. This review summarizes the best-available evidence to provide a clinical update for dermatologists on the approved and emerging indications of photodynamic therapy. The body of evidence suggests that photodynamic therapy is superior or noninferior to other available treatment modalities for actinic keratoses, low-risk basal cell carcinomas, Bowen's disease, skin field cancerization, chemoprevention of keratinocyte carcinomas in organ transplant recipients, photoaging, acne vulgaris, and cutaneous infections including verrucae, onychomycosis, and cutaneous leishmaniasis. There is emerging evidence that photodynamic therapy plays a role in the management of actinic cheilitis, early-stage mycosis fungoides, extramammary Paget disease, lichen sclerosis, and folliculitis decalvans but there are no comparative studies with other active treatment modalities. Common barriers to topical photodynamic therapy include procedural pain, costs, and the time required for treatment delivery. There is significant heterogeneity in the photodynamic therapy protocols reported in the literature, including different photosensitizers, light sources, number of treatments, time between treatments, and use of procedural analgesia. Topical photodynamic therapy should be considered in the management of a spectrum of inflammatory, neoplastic, and infectious dermatoses. However, more comparative research is required to determine its role in the treatment algorithm for these dermatologic conditions and more methodological research is required to optimize photodynamic therapy protocols to improve the tolerability of the procedure for patients.

Epigallocatechin-3-gallate loaded-zein nanoparticles: Molecular interaction, antioxidant, antienzimatic, hemolytic and cytotoxic activities

Epigallocatechin-3-gallate (EGCG) has demonstrated remarkable antioxidant and antienzymatic activities. Nonetheless, its therapeutic use is limited due to its biopharmaceutical characteristics. Zein has become a prominent material for nano delivery systems, providing stability, biocompatibility and biodegradability for therapeutic agents. In this study, zein nanoparticles loaded with EGCG at 288 µg/ml (ZNp-EG288), produced by nanoprecipitation, were characterized and evaluated regarding their antioxidant (DPPH), antielastase, anticollagenase, anti-hyaluronidase and cytotoxicity activities. An EGCG solution prepared in the same conditions (EGCG288) was used for comparison purposes. Molecular Docking was performed to understand the mode of interaction between EGCG and zein to form the nanoparticles and also to evaluate the binding affinity over elastase, collagenase and hyaluronidase, while NMR techniques were used to experimentally confirm the binding and to study the hydration of EGCG in its complexes with zein. Also, the hemolytic potential and the cytotoxicity were evaluated over erythrocytes, immortal human keratinocyte (HaCaT) and squamous carcinoma (A431) cells. The obtained ZNp-EG288 nanoparticles (251.8 nm) were spherical, monodisperse and positively charged (+27.4 mV). ZNp-EG288 presented an encapsulation efficiency and loading of 98.6% and 28.4%, respectively, together with a sustained release over 48 h. Both ZNp-EG288 and EGCG288 demonstrated high antioxidant activity, with an IC50 of 8.26 and 12.34 μg/mlL after 48 h, respectively. The EGCG nanoencapsulation resulted in a good anticollagenase activity (44.44%) and enhanced the antielastase (94.08%) and antihyaluronidase (22.09%) activities compared to EGCG288 (74.02 and 13.03%, respectively). The interaction studies both in silico and by NMR reinforced these results and demonstrated that the activity of EGCG was increased due to selective interactions to zein. Finally, ZNp-EG288, BZNp and EGCG288 were found non-hemolytic, while the treatment with ZNp-EG288 was less cytotoxic than EGCG288 in both cell lines studied (∼27%). Therefore, the nanoencapsulation in zein nanoparticles decreased the cytotoxicity of EGCG. Accordingly, EGCG-loaded zein nanoparticles improved key biological properties related to the skin's antiaging and repairing mechanisms and could become a good stretegy for pharmaceutical and/or skin care products.

Skin cancer and HIV

The risk of skin cancer in persons living with HIV (PLWH) is an evolving subject area shaped by the use of antiretroviral therapy. Keratinocyte carcinomas, including basal cell carcinoma and squamous cell carcinoma, have a high incidence in the general population as well as in PLWH. PLWH may have a higher risk of squamous cell carcinoma when compared to the general population. In addition, Merkel cell carcinoma and sebaceous carcinoma exhibit higher incidence rates in PLWH. Data on melanoma risk are varied. Risks of skin cancer may be influenced by vigilant surveillance, photosensitivity, and immune status. Screening for skin cancer is generally recommended, although national guidelines vary in specific recommendations. Treatments range from topical therapies to surgeries to immune checkpoint inhibitors, with Mohs micrographic surgery playing an important role. Data on immune checkpoint inhibitors suggest safe and efficacious use in PLWH, although larger trials are warranted. The dynamic interplay among HIV, antiretroviral use and immunosuppression, and the risk and treatment of skin cancer underscores the importance of rigorous research studies and screening and treatment guidelines specific to this population.

Melanoma risk in skin of colour patients with a history of a keratinocyte carcinoma.

This manuscript uses individual-level data from 5 million Medicare beneficiaries to investigate the risks of melanoma in skin of color patients with a history of keratinocyte carcinoma. Despite worse melanoma outcomes, skin of color patients are often excluded from skin cancer literature. We found that skin of color patients with a history of keratinocyte carcinoma are at a significantly increased risk of melanoma, though their absolute risk is low.

Keratinocyte Carcinoma Incidence by Race and Ethnicity in Older Adults With Medicare Coverage

This cohort study examines raw and age-adjusted differences in the incidence of keratinocyte carcinoma among Medicare beneficiaries by race and ethnicity.

Skin Cancer Awareness and Knowledge About Sun Protection Practices in Solid Organ Transplant Recipients: Patient Survey Study.

Adequate sun protection practices in chronically immunosuppressed patients can minimize the burden of the most common type of skin cancer in this population. In addition, early recognition of skin cancer by patients can lead to decreased morbidity, and possibly mortality from the disease. Nevertheless, there are significant gaps in the knowledge of sun protection measures and early recognition of skin cancer. The aim of this study is to determine the risk factors of solid organ transplant recipients (SOTRs) for developing skin cancer and their sun exposure education and behavior post-transplantation. This study evaluates the responses of 107 SOTRs on their outlooks and beliefs of sunscreen usage, skin cancer, and sun exposure knowledge. Our study identified several significant risk factors for the development of actinic keratosis or keratinocyte carcinoma in SOTRs including history of sunburn before age 18, blue eyes, history of tanning bed use, performing monthly skin exams, ability to identify precancerous skin lesions, and history of previous skin examinations. A patient-centered approach needs to be used to properly educate patients on effective ways to reduce excessive sun exposure. Regular skin examinations, and patients continued education are necessary components in reducing the burden of skin cancer in SOTRs.

Management of periocular keratinocyte carcinomas with Mohs micrographic surgery and predictors of complex reconstruction: a retrospective study

BackgroundSkin cancer is the most frequent cancer worldwide and the most frequent periocular tumor. Keratinocyte Carcinomas (KC) located in periorificial areas, such as periocular tumors, are considered high-risk tumors. Mohs Micrographic Surgery (MMS) is considered the first line for the treatment of high-risk KC, providing a lower recurrence rate than conventional wide excision. ObjectiveTo describe the clinical-pathological features of periocular KC treated with MMS in a tertiary university center in Chile. MethodsA single-center, retrospective study of patients with KC located on the periocular area, that underwent MMS between 2017‒2022. MMS details were recorded. ResultsOne hundred thirteen patients with periocular carcinomas were included. The mean age was 59 ± 13 years; 52% were women. The most frequent location was the medial canthus (53%), followed by the lower eyelid (30.1%). The most frequent BCC histology was the nodular variant (59.3%). Regarding MMS, the average number of stages was 1.5 ± 0.7, and 54% of the cases required only 1 stage to achieve clear margins. To date, no recurrence has been reported. Tumors larger than 8.5 mm in largest diameter or 43.5 mm2 were more likely to require complex reconstruction. Study limitationsRetrospective design and a relatively low number of patients in the SCC group. Possible selection bias, as larger or more complex cases, may have been referred to oculoplastic surgeons directly. ConclusionThe present study confirms the role of MMS for the treatment of periocular KCs. Periocular KCs larger than 8.5 mm might require complex reconstruction. These results can be used to counsel patients during pre-surgical visits.

Mohs Appropriate Use Criteria Scores and Treatment of Keratinocyte Carcinoma: Review of 11,145 Tumors

Background: Various methods are available for treatment of keratinocyte carcinomas (KCs). The Mohs appropriate use criteria (AUC) score was developed to quantify the appropriateness of Mohs micrographic surgery (MMS) based on multiple tumor and patient characteristics. Objectives: Stratify KCs by treatment modality used and compare to Mohs AUC score. Methods: Conducted a retrospective review of 11,145 consecutive KCs between 01/2017 and 12/2021, comparing associated Mohs AUC score with modality selected. Results: The average Mohs AUC score for all KCs combined was 7.1 with 8714 (78.2%) qualifying for MMS via AUC score. However, MMS was only done on 2813 (32.3%) of KCs. Excisional surgery was used to treat 4580 (41.1%) of KCs, 2777 (24.9%) were treated with electrodesiccation and curettage (ED&C), and 732 (6.6%) were treated with biopsy only. Of those KCs treated with excision, ED&C, or a biopsy, 70.7%, 70.7%, and 72.4% reached an “appropriate” Mohs AUC score for MMS respectively. Limitations: This is a single private practice, with two board certified dermatologists Conclusions: Mohs AUC score can help determine if a KC warrants MMS; however, in our practice, MMS was necessary for only 32.3% of the KCs that qualified based on the Mohs AUC score.

Melanoma and CLL co-occurrence and survival: role of KC history

BackgroundSurvival following melanoma and chronic lymphocytic leukemia (CLL) have both been individually associated with previous history of non-melanoma skin cancers (specifically keratinocyte carcinomas [KC]). Furthermore, melanoma and CLL have been reported to occur within the same patients. The survival experience of patients with both cancers is understudied, and the role of history of KC is unknown. Additional research is needed to tease apart the independent associations between KC and CLL survival, KC and melanoma survival, and the co-occurrence of all three cancers.MethodsA retrospective cohort study was conducted among patients who were diagnosed with melanoma and/or CLL at a comprehensive cancer center between 2008 and 2020. Multivariable Cox regression models were used to examine the association between history of KC and survival following melanoma and/or CLL with careful consideration of calendar year of diagnosis, treatment regimens and other risk factors. A nested case–control study comparing patients with both CLL and melanoma to those with only CLL or only melanoma was conducted to compare blood parameters across the three groups.ResultsA time-dependent association was observed between history of KC and favorable melanoma survival within 4 years following diagnosis and poorer survival post 7 years after melanoma diagnosis. History of KC was not significantly associated with survival following the diagnosis of CLL, after adjustment for clinical factors including historical/concurrent melanoma. Patients with co-occurring melanoma and CLL tended to be diagnosed with melanoma first and had elevated blood parameters including white blood cell and lymphocyte counts as compared with patients who were diagnosed with only melanoma.ConclusionsHistory of KC was an independent predictor of survival following melanoma but not of CLL. Additional studies are needed to determine if blood parameters obtained at the time of melanoma diagnosis could be used as a cost-effective way to identify those at high risk of asymptomatic CLL for the promotion of earlier CLL diagnosis.

Oral Nicotinamide for Actinic Keratosis Prevention in Kidney Transplant Recipients: A Pilot Double-Blind, Randomized, Placebo-Controlled Trial

Oral nicotinamide (NAM) has shown promise in preventing actinic keratoses (AKs) in trials based outside of the United States. We assessed the efficacy of oral NAM supplementation in kidney transplant recipients with a history of keratinocyte carcinoma. Patients enrolled in a 2-week run-in phase, during which NAM 1000 mg was taken twice daily. After a washout period, patients who tolerated the run-in phase were randomized to NAM 500 mg twice daily or placebo. At baseline, 4, 8, and 12 months, dermatologists conducted full-body skin exams to document area-specific AKs. Routine lab work was collected to ensure the stability of renal allograft function. The dosage was reduced from 1000 to 500 mg due to gastrointestinal symptoms in the run-in phase. Patients were randomized to NAM (n=10) or placebo (n=11). At 12 months, mean AK count was 30.8 (95% CI -11.7-73.4) for NAM and 26.6 (95% CI 10.8-42.5) for placebo. The difference in percent AK count change at 12 months compared with baseline was 259.8% (95% CI -385.9 to 905.5) for NAM and 72.4% (95% CI -118.6 to 263.5) for placebo. The between-group difference in percent AK change was not significant (P=.38). There was no attrition in the placebo group and 40% attrition in the NAM arm. Nicotinamide did not decrease AK development among kidney transplant recipients. Limitations include drug tolerability, small sample size, and single-center trial nature.

Exogenous hormone therapy and non-melanoma skin cancer (keratinocyte carcinoma) risk in women: a systematic review and meta-analysis

Previous studies reported inconsistent results regarding the association between keratinocyte carcinoma (KC) and exogenous hormone therapy. This study aimed to investigate the association between the use of exogenous sex hormones and the risk of KC among women. The databases of PubMed, Ovid Medline, Cochrane, and Web of Science were searched until May 2023. A total of 5293 patients with KC and 106,424 controls were included for analysis. The meta-analysis indicated that oral contraceptives (OC) and hormonal replacement therapy (HRT) use were associated with an increased risk of squamous cell carcinoma (SCC) (OR/RR = 1.25, 95% CI 1.10 to 1.43, I2 = 41.6%, p = 0.080). Subgroup analysis showed that OC use increased the risk of SCC (OR/RR = 1.37, 95% CI 1.15 to 1.63), whereas no significant association was shown between HRT use and risk of SCC (OR/RR = 1.13, 95% CI 0.93 to 1.37). Additionally, OC and HRT use were linked to an increased risk of basal cell carcinoma (BCC) (OR/RR = 1.16, 95% CI 1.09 to 1.25, I2 = 30.1%, p = 0.188). Further subgroup analysis suggested both OC and HRT use were associated with an increased risk of BCC (OC: OR/RR = 1.13, 95% CI 1.01 to 1.25; HRT: OR/RR = 1.19, 95% CI 1.09 to 1.30). In conclusion, our findings support the hypothesis that the risk of KC among women may be affected by the use of exogenous hormones.

Risk of keratinocyte carcinomas following extracorporeal photopheresis among lung transplant recipients: A retrospective cohort study

Risk of keratinocyte carcinomas following extracorporeal photopheresis among lung transplant recipients: A retrospective cohort study

Quality of Life Before and After Radiation Therapy for Early-Stage Keratinocyte Carcinoma: A Longitudinal Analysis

Little is known about patient-reported quality of life (QOL) before and after radiotherapy (RT) for early keratinocyte carcinoma (KC). The present study tested the hypothesis that QOL is hypothesized to deteriorate soon after RT, with subsequent improvement of a magnitude similar to other KC treatments. This observational study assessed prospectively collected longitudinal patient-reported QOL data at a single center. Patients undergoing external beam RT for early-stage (T0-2, <4 cm) KC that completed the Skindex-16 (S16) or Skin Cancer Index (SCI) before and at least once after RT were included. These indices include subscales of symptoms, emotions, and functioning for S16 and emotional, social, and appearance for SCI. 81 patients (median age 79 years) were treated for early KC, most being basal cell carcinomas (87%) on the face (80%) an average of 1.3 cm in diameter. Composite S16 scores and total SCI scores showed significant, clinically meaningful improvements at 3 months and 6 weeks after RT, respectively. QOL declined at 6 weeks after treatment on the S16 symptoms subscale. Concurrently, S16 and SCI emotional subscales significantly improved, and this trend persisted for 2+ years. Improvements in S16 functioning and SCI social and appearance QOL occurred after RT. The magnitude of improvement in QOL 3-12 months after RT was comparable to what has been previously reported after other types of KC treatments, like surgery. QOL related to symptoms deteriorates during the first 6 weeks after RT for early KC, but it improves by 3 months. QOL related to emotions, functioning, social, and appearance all improve after RT. These changes in QOL are similar to those observed after other treatments of early KC.