Risk Factor For Non-melanoma Skin Cancer Research Articles

Certolizumab Pegol Treatment in Patients With Crohn's Disease: Final Safety Data From the SECURE Registry.

Crohn's disease (CD) treatment is associated with increased risks of infection and malignancies. Although the safety of certolizumab pegol (CZP) is well established, long-term data from community-based observational studies are lacking. This study aimed to evaluate long-term safety outcomes of patients from the SECURE registry receiving CZP relative to other CD treatments, including corticosteroids, immunosuppressants, and biologics. The primary outcome of this observational study was the evaluation of malignancies. Adult patients with CD were prospectively monitored for up to 8 years. Pre-specified data were collected for all enrolled patients. Adverse events of interest (AEoIs) were reported per 100 patient-years (PY) of exposure. Incidence rate ratios (IRRs) were calculated for AEoIs using multivariate regression analysis accounting for exposure to multiple treatments. Malignancies reported after any exposure to CZP were attributed to CZP. Post-hoc analyses were conducted to evaluate non-melanoma skin cancer (NMSC), lymphoma, and pregnancy outcomes. A total of 3072 patients were enrolled in the study. The risk of AEoIs was similar between patients with only CZP exposure versus comparator exposure. Among patients with any CZP exposure, there was a higher frequency of serious infections (IRR: 2.56 [95% confidence interval (CI): 2.00, 3.29]) and hypersensitivity or anaphylactic reactions (IRR: 4.11 [95% CI: 1.80, 9.38]) versus patients with comparator exposure. Malignancy rates were similar across groups; however, concomitant use of thiopurines was associated with higher odds of NMSC (odds ratio: 2.30 [95% CI: 1.09, 4.89]). Most cases of lymphoma (5/7) occurred in patients with exposure to thiopurines. Pregnancy outcomes were similar across groups. No new safety signals were identified for CZP; the use of thiopurines was identified as a risk factor for NMSC. NCT00844285.

What does the general population know about nonmelanoma skin cancer? Representative cross-sectional data from Germany

Abstract Aim Nonmelanoma skin cancer (NMSC) is the most common form of cancer in white-skinned populations. However, there is a lack of comprehensive research on the general population’s knowledge about NMSC. Subjects and methods As part of wave 8 of the German National Cancer Aid Monitoring (NCAM), 4000 participants aged 16–65 years (49.3% female) were interviewed by telephone about NMSC. Questions included awareness of (colloquial) terms for NMSC, its signs, consequences, risk factors, prevalence, and severity. Results Colloquial terms for skin cancer were heard of more often than medical terms (60.9–82.1% vs. 22.6–51.5%). In our sample, there was little familiarity with signs (15.8–36.4%), possible consequences (14.7–56.3%), prevalence (27.4%), and severity (29.0%) of NMSC. Most participants knew about UV-related risk factors for NMSC (73.0–78.7%). Women, those with higher education levels, full-time employment, lighter skin type, presence of more than 40 nevi, frequent childhood sunburns, or frequent intentional tanners achieved a higher knowledge score. Concern about NMSC was associated with more NMSC knowledge. Conclusion We found knowledge gaps regarding signs, consequences, and prevalence of NMSC. To ensure early recognition and treatment, the general population should be further educated, specifically targeting male, less educated, and unemployed individuals.

"Well, to Be Honest, I Don't Have an Idea of What It Might Be"-A Qualitative Study on Knowledge and Awareness Regarding Nonmelanoma Skin Cancer.

Nonmelanoma skin cancer (NMSC) is the most common cancer type in Western industrialized countries. However, research into the knowledge and awareness in the general population regarding NMSC is still scarce. This qualitative study aims to fill this research gap. Face-to-face, semi-structured interviews with 20 individuals aged 55-85 years were conducted between February and October 2020. Transcribed interviews were analyzed using qualitative content analysis. The term "white skin cancer"-the German colloquial term of NMSC-was well-known, but the incidence was underestimated. None of the participants could give a precise definition of NMSC, and various alterations in the skin were, partially wrongly, stated as potential signs for NMSC. As risk factors for NMSC, solar radiation, and fair skin type were mentioned most often. The perceived individual risk of developing NMSC and risk compared to individuals of the same age and gender were low in our sample. Own knowledge about NMSC was mostly perceived to be insufficient, and the majority of the sample would like to receive more information on NMSC. Our results emphasize a need to inform about the signs and risks of NMSC not only in the studied older age group but also in younger people.

P8.042: Non-melanoma Skin Cancer With an Aggressive Course in Kidney Transplant Patients Treated With Rapamycin

Introduction: Non-melanoma skin cancer (NMSC) represents the most frequent malignancy in patients with solid organ transplantation, with a high risk of metastasis (MTS) and death related to factors such as chronic immunosuppression, exposure to ultraviolet (UV) radiation, and HPV infections. Objectives: • To describe the features of non-melanoma skin cancer (NMSC). • To report the development of multiple NSCLC and metastasis in patients treated with rapamycin. • To highlight the need for dermatological control in order to assess risk factors, precancerous lesions and make an early diagnosis. Materials and methods: We present three renal transplant patients assisted by Dermatology at the Renal Transplant Unit of CRAI Sur, Hospital Interzonal General de Agudos “Gral. San Martín”, La Plata, Argentina. Patients with multiple lesions under treatment with rapamycin and aggressive evolution were chosen. Risk factors related to the multiplicity and dismal evolution of NCC (signs of photodamage, preneoplastic lesions, history of NCC) were evaluated prior to evaluation at the unit; we also analysed age of presentation, sex, transplantation timing, initial immunosuppressive regimen and subsequent modifications, type of NMSC, treatment and evolution. Patients:Case 1: 68 year-old male, with prior history of basal cell carcinomas (back and face) and actinic keratoses. He developed multiple squamous cell carcinoma 5 years post transplantation. Induction: thymoglobulin. Immunosuppression: rapamycin, MMF and steroids. Therapy: surgery. Death due to multiple lung MTS. Case 2: 69 year-old male, with prior history of actinic keratoses and basal cell carcinoma (face). He developed multiple metatypic basal cell carcinoma 9 years post-transplantation. Induction: Basiliximab. Immunosuppression: tacrolimus, MMF and steroids. Switch to rapamycin after diagnosis. Therapy: surgery and Imiquimod. Death due to acute myocardial infarction. Case 3: 43 year-old male, with prior history of actinic keratoses and squamous cell carcinoma (face). He developed squamous cell carcinoma (face) and multiple skin MTS 7 years post-transplantation. Induction: thymoglobulin. Immunosuppression: tacrolimus, MMF and steroids. Switch to rapamycin after diagnosis. Therapy: chemotherapy. Death due to multiple lung MTS. Conclusions: 1- The NMSC in these patients presented with multiple lesions and clinical and histological characteristics related to an aggressive course (MTS and death in two cases). 2- Immunosuppressive therapy with rapamycin did not modify the outcome and development of multiple lesions despite its known antiproliferative and angiogenesis effects. 3- All our patients were men and presented risk factors for NMSC (photodamage, actinic keratoses, more than five years post-transplantation, history of prior NMSC, induction and immunosuppressive therapy). 4- Dermatological control is crucial in order to identify risk factors, promote photoeducation and make a prompt diagnosis.

Arsenic and chromium levels in hair correlate with actinic keratosis/non-melanoma skin cancer: results of an observational controlled study.

The role of heavy metals in carcinogenetic process has been widely established; however, information on the most common environmental metals that serve as major risk factors for actinic keratosis (AK)/non-melanoma skin cancer (NMSC) are still lacking. The aim of this study was to evaluate levels of the most common environmental heavy metals in hair of patients with AK/NMSC as compared to healthy controls. Thirty-one patients diagnosed with AK/NMSC and 34 healthy controls were enrolled. Patients were interviewed for heavy metals exposure and underwent hair analysis for detection of arsenic (As), cadmium (Cd), chromium (Cr), nickel (Ni) and lead (Pb). Continuous variables were analyzed using Wilcoxon Non-Parametric Rank Test and proportions were compared by Fisher's Exact Test. Statistical significance was determined by P<0.05. In our cohort we observed 48.4% patients had AKs, 16.1% basal cell carcinoma (BCC), 9.7% squamous cell carcinoma (SCC) and 25.9% of patients presented with a combination of these lesions. There were significantly elevated levels of As and Cr in AK-NMSC group as compared to controls. We identified a strong positive correlation between As and Cr concentration and AK/NMSC adding new clues to the scenery of NMSC risk factors that should be taken under consideration in exposed populations.

P260 An analysis of non-melanoma skin cancer rates in the tofacitinib Ulcerative Colitis clinical programme

Abstract Background Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of ulcerative colitis (UC). We present an updated analysis of non-melanoma skin cancer (NMSC) events in the tofacitinib UC clinical programme, including final data from the open-label, long-term extension (OLE) study (as of 24 Aug 2020). Methods NMSC events were evaluated from 3 randomised, placebo (PBO)-controlled studies (2 Phase [P]3 induction studies [NCT01465763; NCT01458951]; 1 P3 maintenance study [NCT01458574]) and an OLE study (NCT01470612), as 3 cohorts: Induction (P3 induction studies [patients (pts) receiving tofacitinib 10 mg twice daily (BID) or PBO]); Maintenance (P3 maintenance study [pts receiving tofacitinib 5 or 10 mg BID or PBO]); Overall (pts receiving tofacitinib 5 or 10 mg BID in P3 or OLE studies). Analysis was by predominant dose (PD) 5 or 10 mg BID, based on average daily dose &amp;lt;15 or ≥15 mg, respectively (82% of pts received PD 10 mg BID). An independent adjudication committee reviewed potential NMSC. Proportions and incidence rates (IRs; unique pts with events per 100 pt-years of exposure) were evaluated for NMSC. A Cox proportional hazards model was used for risk factor analysis. Results 1124 pts were evaluated for NMSC (2809.4 pt-years of tofacitinib exposure; up to 7.8 years of treatment; median duration 685.5 days). NMSC events in Induction and Maintenance were previously reported (Table 1).1 In Overall, NMSC occurred in 21 pts (IR 0.73 [95% confidence interval (CI) 0.45, 1.12]): PD tofacitinib 5 mg BID n=5, IR 0.63 (0.21, 1.48); PD tofacitinib 10 mg BID n=16, IR 0.77 (0.44, 1.25) (Table 1); 2 new cases since May 2019.1 Eleven pts had squamous cell carcinoma and 15 pts had basal cell carcinoma; 5 pts had both. No NMSC was metastatic or led to discontinuation. IRs by time interval and subgroup are reported (Table 2). Prior NMSC (hazard ratio [HR] 12.08 [95% CI 4.20, 34.76]) and age (per 10-year increase, HR 2.01 [1.38, 2.93]) were significant risk factors for NMSC in the multivariable analysis. Prior immunosuppressant use was not a significant risk factor in either the multivariable or univariate analyses. Conclusion In this analysis, NMSC IRs for tofacitinib were similar to those in pts with UC treated with biologics2 and those previously reported in the tofacitinib UC clinical programme.1 NMSC events were more likely to occur in pts with recognised NMSC risk factors: prior NMSC and increasing age.3 Dose dependency of NMSC IR could not be concluded here, as dose changes were permitted. NMSC IRs remained stable over time, up to 7.8 years of exposure. References

Tofacitinib for the Treatment of Ulcerative Colitis: Analysis of Nonmelanoma Skin Cancer Rates From the Ulcerative Colitis Clinical Program.

BackgroundTofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of ulcerative colitis (UC). We present integrated analyses of nonmelanoma skin cancer (NMSC) incidence in the tofacitinib UC clinical program.MethodsNonmelanoma skin cancer events were evaluated from 3 randomized, placebo-controlled studies: 2 identical, 8-week induction studies (NCT01465763, NCT01458951), a 52-week maintenance study (NCT01458574), and an open-label, long-term extension study (NCT01470612). Cohorts analyzed were: Induction, Maintenance, and Overall (patients receiving ≥1 dose of tofacitinib 5 mg or 10 mg twice daily [BID]). An independent adjudication committee reviewed potential NMSC. Proportions and incidence rates (IRs; unique patients with events per 100 patient-years of exposure) for NMSC were evaluated. A Cox proportional hazards model was used for risk factor analysis.ResultsNonmelanoma skin cancer was evaluated for 1124 patients (2576.4 patient-years of tofacitinib exposure; ≤6.8 years’ treatment). In the Induction Cohort, NMSC IR was 0.00 for placebo and 1.26 for 10 mg BID. Nonmelanoma skin cancer IR was 0.97 for placebo, 0.00 for 5 mg BID and 1.91 for 10 mg BID in the Maintenance Cohort, and 0.73 (n = 19) in the Overall Cohort. No NMSC was metastatic or led to discontinuation. In the Overall Cohort, Cox regression identified prior NMSC (hazard ratio [HR], 9.09; P = 0.0001), tumor necrosis factor inhibitor (TNFi) failure (3.32; P = 0.0363), and age (HR per 10-year increase, 2.03; P = 0.0004) as significant independent NMSC risk factors.ConclusionsFor patients receiving tofacitinib, NMSC occurred infrequently. Older age, prior NMSC, and TNFi failure, which are previously reported NMSC risk factors in patients with UC, were associated with increased NMSC risk.

Use of hydrochlorothiazide and risk of nonmelanoma skin cancer in Koreans: a retrospective cohort study using administrative healthcare data.

The incidence of skin cancer is increasing because of the ageing population and ultraviolet exposure, and previous studies have revealed that long-term use of hydrochlorothiazide (HCTZ), an antihypertensive agent, has been associated with an increased risk of nonmelanoma skin cancer (NMSC). However, the association of NMSC and HCTZ within East Asian populations is unclear. To investigate the risk of NMSC in Korean subjects using HCTZ. A retrospective cohort study was conducted using the administrative healthcare data. The study enrolled 62243 patients exposed to HCTZ with a cumulative dose of ≥ 2500mg and 62243 unexposed subjects matched 1 : 1 with the patients for age, sex and income level. There was a significant difference in the cumulative incidence of NMSC between the two groups (log-rank P<0.01). Cox regression analysis was conducted after adjusting for potential confounders, and showed the risk for NMSC in the group exposed to HCTZ was significantly higher than that of the unexposed group (hazard ratio=1.48; 95% CI 1.03-2.13). In the subgroup analysis, the oldest age group (≥ 70years) showed increased cumulative incidence of NMSC with statistical significance compared with the unexposed control group (log-rank P<0.01). In this study, we revealed that the cumulative use of HCTZ (≥ 2500mg) could increase the risk of NMSC in Koreans, especially the older age group. Thus, HCTZ could be a risk factor for NMSC in East Asian as well as white populations.

Second primary malignancy in myelofibrosis patients treated with ruxolitinib.

Ruxolitinib (RUX), the first JAK1/JAK2 inhibitor approved for myelofibrosis (MF) therapy, has recently been associated with the occurrence of second primary malignancies (SPMs), mainly lymphomas and non-melanoma skin cancers (NMSCs). We analyzed the incidence, risk factors and outcome of SPMs in 700 MF patients treated with RUX in a real-world context. Median follow-up from starting RUX was 2·9years. Overall, 80 (11·4%) patients developed 87 SPMs after RUX start. NMSCs were the most common SPMs (50·6% of the cases). Multivariate analysis demonstrated that male sex [hazard ratio (HR): 2·37, 95% confidence interval (95%CI): 1·22-4·60, P=0·01] and thrombocytosis>400×109 /l at RUX start (HR:1·98, 95%CI: 1·10-4·60, P=0·02) were associated with increased risk for SPMs. Risk factors for NMSC alone were male sex (HR: 3·14, 95%CI: 1·24-7·92, P=0·02) and duration of hydroxycarbamide and RUX therapy>5years (HR: 3·20, 95%CI: 1·17-8·75, P=0·02 and HR: 2·93, 95%CI: 1·39-6·17, P=0·005 respectively). In SPMs excluding NMSCs, male sex (HR: 2·41, 95%CI: 1·11-5·25, P=0·03), platelet>400×109 /l (HR: 3·30, 95%CI: 1·67-6·50, P=0·001) and previous arterial thromboses (HR: 3·47, 95%CI: 1·48-8·14, P=0·004) were shown to be associated with higher risk of SPMs. While it is reassuring that no aggressive lymphoma was documented, active skin surveillance is recommended in all patients and particularly after prolonged hydroxycaramide therapy; oncological screening should be triggered by thrombocytosis and arterial thrombosis, particularly in males.

S0787 An Update on the Analysis of Non-Melanoma Skin Cancer in the Tofacitinib Ulcerative Colitis Clinical Program as of May 2019

INTRODUCTION: Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of UC. We present an updated [1] analysis of non-melanoma skin cancer (NMSC) events in the tofacitinib UC clinical program as of May 2019. METHODS: NMSC events were evaluated from 3 randomized, placebo-controlled studies (2 Phase [P]3 induction studies [NCT01465763; NCT01458951] and 1 maintenance P3 study [NCT01458574]) and an ongoing, open-label, long-term extension (OLE) study (NCT01470612). Three cohorts were analyzed: Induction (P3 induction studies), Maintenance (P3 maintenance study), and Overall (patients [pts] receiving tofacitinib 5 or 10 mg twice daily [BID] in P3 or OLE studies). Analysis was by predominant dose (PD) 5 or 10 mg BID, based on average daily dose < 15 mg or ≥ 15 mg, respectively (82.4% of pts assigned PD 10 mg BID). An independent adjudication committee reviewed potential NMSC. Proportions and incidence rates (IRs; unique pts with events per 100 pt-years [PY] of exposure) were evaluated for NMSC. A Cox proportional hazards model was used for risk factor analysis. RESULTS: 1,124 pts were evaluated for NMSC (2,576.4 PY of tofacitinib exposure; ≤ 6.8 years of treatment). NMSC events in the Induction and Maintenance Cohorts were previously reported (Table) [1]. NMSC occurred in 19 Overall Cohort pts (IR 0.73 [95% confidence interval (CI) 0.44, 1.13]; PD tofacitinib 5 mg BID, n = 3, IR 0.45 [0.09, 1.30]; PD tofacitinib 10 mg BID, n = 16, IR 0.82 [0.47, 1.34]) (Table); no new cases since Sep 2018 [1]. No NMSC was metastatic or led to discontinuation. Prior NMSC (hazard ratio [HR] 9.09 [95% CI 2.98, 27.73]), prior tumor necrosis factor inhibitor (TNFi) failure (HR 3.32 [1.08, 10.20]), and age (per 10-year increase, HR 2.03 [1.37, 3.02]) were significant risk factors for NMSC. CONCLUSION: NMSC events were infrequent with tofacitinib treatment and more likely to occur in pts with prior NMSC, prior TNFi failure, and with increasing age – known NMSC risk factors [2]. Dose dependency of NMSC IR could not be concluded here, as dose changes were permitted. NMSC IRs were similar to those previously reported in the tofacitinib UC clinical program [1] and in pts with UC treated with biologics [3].Table 1

Arsenic and chromium levels in hair correlate with actinic keratosis/non melanoma skin cancer: results of an observational controlled study

The role of heavy metals in carcinogenetic process has been widely established; however, information on the most common environmental metals that serve as major risk factors for actinic keratosis (AK)/non-melanoma skin cancer (NMSC) are still lacking. The aim of this study was to evaluate levels of the most common environmental heavy metals in hair of patients with AK/NMSC as compared to healthy controls. Thirty-one patients diagnosed with AK/NMSC and 34 healthy controls were enrolled. Patients were interviewed for heavy metals exposure and underwent hair analysis for detection of arsenic (As), cadmium (Cd), chromium (Cr), nickel (Ni) and lead (Pb). Continuous variables were analyzed using Wilcoxon Non-Parametric Rank Test and proportions were compared by Fisher's Exact Test. Statistical significance was determined by P<0.05. In our cohort we observed 48.4% patients had AKs, 16.1% basal cell carcinoma (BCC), 9.7% squamous cell carcinoma (SCC) and 25.9% of patients presented with a combination of these lesions. There were significantly elevated levels of As and Cr in AK-NMSC group as compared to controls. We identified a strong positive correlation between As and Cr concentration and AK/NMSC adding new clues to the scenery of NMSC risk factors that should be taken under consideration in exposed populations.

Beta Human Papillomavirus and Merkel Cell Polyomavirus in Skin Neoplasms

Beta Human Papillomavirus and Merkel Cell Polyomavirus in Skin Neoplasms

671 An Update on the Analysis of Non-Melanoma Skin Cancer in the Tofacitinib Ulcerative Colitis Program

INTRODUCTION: Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of ulcerative colitis (UC). We present an updated integrated analysis of non-melanoma skin cancer (NMSC) events in the tofacitinib UC clinical program as of Sep 2018. METHODS: NMSC events were evaluated from 4 randomized, placebo-controlled studies (Phase [P] 2 and P3 induction studies [NCT00787202; NCT01465763; NCT01458951], a maintenance P3 study [NCT01458574]), and an ongoing, open-label, long-term extension (OLE) study (NCT01470612). 1–3 Three cohorts were analyzed: Induction (P2/P3 induction studies); Maintenance (P3 maintenance study); Overall (patients [pts] receiving ≥1 dose of tofacitinib 5 or 10 mg twice daily [BID] in P2, P3, or ongoing OLE studies). For P3 studies, a blinded independent adjudication committee reviewed potential NMSC. Proportions and incidence rates (IRs; unique pts with events per 100 pt-years [PY] of exposure) for NMSC were evaluated. A Cox proportional hazards model was used for risk factor analysis. RESULTS: 1124 pts were evaluated for NMSC (P3 studies only), with 2399 PY of tofacitinib exposure and up to 6.1 years of treatment. NMSC occurred in 2 Induction tofacitinib-treated pts, 1 Maintenance placebo-treated pt (IR 0.97), 3 Maintenance 10 mg BID pts (IR 1.91), and 19 Overall Cohort pts (IR 0.78). 10 pts had squamous cell carcinoma (SCC) and 12 pts had basal cell carcinoma (BCC); 3 pts had both SCC and BCC (Table). No NMSC was metastatic or led to discontinuation. The Overall Cohort showed higher IRs for pts aged ≥50 years vs other subgroups and for pts with prior tumor necrosis factor inhibitor treatment, or prior immunosuppressant use vs those without (Table 1). Prior NMSC (hazard ratio [HR] 10.95; 95% CI 3.72, 32.24; P &lt; 0.0001) and age (HR per 10-year increase 2.10; 95% CI 1.41, 3.13; P = 0.0003) were significant risk factors for NMSC. CONCLUSION: NMSC events were infrequent in the tofacitinib UC program, and were more likely to occur in pts with prior NMSC, and with increasing age – known NMSC risk factors. 4 NMSC IRs were similar to those reported for tofacitinib in rheumatoid arthritis 5 and for biologic UC treatments. 6

DNA methylome and transcriptome alterations and cancer prevention by triterpenoid ursolic acid in UVB-induced skin tumor in mice.

Nonmelanoma skin cancers (NMSCs) are the most common type of skin cancers. Major risk factors for NMSCs include exposure to ultraviolet (UV) irradiation. Ursolic acid (UA) is a natural triterpenoid enriched in blueberries and herbal medicinal products, and possess anticancer activities. This study focuses on the impact of UA on epigenomic, genomic mechanisms and prevention of UVB-mediated NMSC. CpG methylome and RNA transcriptome alterations of early, promotion and late stages of UA treated on UVB-induced NMSC in SKH-1 hairless mice were conducted using CpG methyl-seq and RNA-seq. Samples were collected at weeks 2, 15, and 25, and integrated bioinformatic analyses were performed to identify key pathways and genes modified by UA against UVB-induced NMSC. Morphologically, UA significantly reduced NMSC tumor volume and tumor number. DNA methylome showed inflammatory pathways IL-8, NF-κB, and Nrf2 pathways were highly involved. Antioxidative stress master regulator Nrf2, cyclin D1, DNA damage, and anti-inflammatory pathways were induced by UA. Nrf2, cyclin D1, TNFrsf1b, and Mybl1 at early (2 weeks) and late (25 weeks) stages were identified and validated byquantitative polymerase chain reaction. In summary, integration of CpG methylome and RNA transcriptome studies show UA alters antioxidative, anti-inflammatory, and anticancer pathways in UVB-induced NMSC carcinogenesis. Particularly, UA appears to drive Nrf2 and its upstream/downstream genes, anti-inflammatory (at early stages) and cell cycle regulatory (both early and late stages) genes, of which might contribute to the overall chemopreventive effects of UVB-induced MNSC. This study may provide potential biomarkers/targets for chemoprevention of early stage of UVB-induced NMSC in human.

Treg lymphocytes and cutaneous viral infections

Approximately three million non‐melanoma skin cancers (NMSCs) are diagnosed worldwide each year, although this number is likely an underestimate given that these cancers are not always recorded in cancer registries. Studies have suggested that skin (cutaneous) infections with human papillomaviruses (HPV) and polyomaviruses (HPyV) may play a role in the development of some NMSC types. Suppression of the immune system is also a risk factor for NMSC. This study, from the U.S.A, aimed to understand the relationship between T‐regulatory (Treg) cells, cells which suppress immune response, and cutaneous viral infections. Blood, skin swabs and eyebrow hairs were collected from 352 patients who underwent skin cancer screening and did not have cancer detected. The researchers examined whether the skin swabs (SSW) and eyebrow hairs (EBH) contained genetic material (DNA) corresponding to 98 cutaneous HPV types (including beta HPV and gamma HPV) and 5 HPyV types. The blood samples were analyzed to determine proportions of different types of Treg cell populations in circulation (in the blood). The researchers found no association between total percent of circulating Treg cells and beta HPV or HPyV infection. However, two types of Treg cells were found at lower levels in those that had gamma HPV infection in their EBH and/or SSW. Those two types were CLA+ Treg cells (known to travel to the skin) and effector CD27‐CD45RA‐FOXP3+CD4+ Treg cells (known to become active when exposed to a foreign viral infection). The study results suggest that gamma HPV infection may stimulate Treg cells to move from circulation into the skin tissues.

Behavioral and demographic factors associated with occurrence of non-melanoma skin cancer in organ transplant recipients.

Non-melanoma skin cancers (NMSC) are the most common epithelial malignancies in organ transplantation recipients (OTRs). In Italy, incidence rates of post-transplantation NMSC are approximately 5% after 5 years and 10% after 10 years since organ transplantation. The objective was to describe risk factors associated with NMSC in a cohort of renal and liver transplant recipients, in a single-center longitudinal study. Renal and liver transplant patients, who underwent transplantation between June 1985 and December 2015, were visited for the first time or followed-up in a dedicated outpatient clinic every six months until July 2016. We included 356 renal and 76 liver transplant patients. 108 OTRs (25.6%) presented 299 NMSC. 74 patients developed actinic keratosis (17.1%), 36 patients squamous cell carcinoma (8.5%), and 52 patients basal cell carcinoma (12.3%). Time from transplantation and kidney transplant were the main risk factors for NMSC. Higher incidences of all NMSC were observed in patients >60 years, males and smokers, while decreased incidences were detected in individuals with higher educational levels. Multiple logistic regression models confirmed that male gender (RR 3.3, P=0.001), cigarette smoking (RR 2.0, P=0.026), light eye color (RR 2.9, P=0.001) and family history of cancer (RR 1.8, P=0.042) were independently associated with NMSC. Dermatological follow-up is important in OTRs, due to the higher risk of tumors and mainly NMSC. Clinical and environmental factors, including cigarette smoking, are useful in characterizing OTR with higher risk of NMSC.

Non Melanoma Skin Cancer Pathogenesis Overview.

(1) Background: Non-melanoma skin cancer is the most frequently diagnosed cancer in humans. The process of skin carcinogenesis is still not fully understood. However, several studies have been conducted to better explain the mechanisms that lead to malignancy; (2) Methods: We reviewed the more recent literature about the pathogenesis of non-melanoma skin cancer focusing on basal cell carcinomas, squamous cell carcinoma and actinic keratosis; (3) Results: Several papers reported genetic and molecular alterations leading to non-melanoma skin cancer. Plenty of risk factors are involved in non-melanoma skin cancer pathogenesis, including genetic and molecular alterations, immunosuppression, and ultraviolet radiation; (4) Conclusion: Although skin carcinogenesis is still not fully understood, several papers demonstrated that genetic and molecular alterations are involved in this process. In addition, plenty of non-melanoma skin cancer risk factors are now known, allowing for an effective prevention of non-melanoma skin cancer development. Compared to other papers on the same topic, our review focused on molecular and genetic factors and analyzed in detail several factors involved in non-melanoma skin cancer.

Risk of cancer in patients with psoriasis on biological therapies: a systematic review.

Biological therapies are highly effective in psoriasis, but have profound effects on innate and adaptive immune pathways that may negatively impact on cancer immunosurveillance mechanisms. To investigate the risk of cancer in patients with psoriasis treated with biological therapy. We searched MEDLINE, Embase, and the Cochrane Library (up to August 2016) for randomized controlled trials, prospective cohort studies and systematic reviews that reported cancer incidence in people exposed to biological therapy for psoriasis compared with a control population. Eight prospective cohort studies met our inclusion criteria. All the evidence reviewed related to tumour necrosis factor inhibitors (TNFi) with the exception of one study on ustekinumab. An increased risk of nonmelanoma skin cancer (NMSC), particularly squamous cell carcinoma, was reported with TNFi compared with both a general United States population and a rheumatoid arthritis population treated with TNFi. No evidence for increased risk of cancers (reported as all cancers, lymphoma, melanoma, prostate, colorectal and breast cancer) other than NMSC was identified. There were important limitations to the studies identified including choice of comparator arms, inadequate adjustment for confounding factors and failure to account for latency periods of cancer. There remains a need for ongoing pharmacovigilance in relation to cancer risk and biological therapy; the NMSC signal requires further investigation to determine the risk specifically attributable to biological therapy using prospectively collected data with adjustment for known NMSC risk factors.

Nichtmelanozytärer Hautkrebs

Non-melanoma skin cancer (NMSC) is the most common malignancy of the light-skinned population with an enormous socioeconomic impact. Historically known as incurable under the term noli me tangere (transl. do not touch me), today various non-melanocytic cutaneous neoplasms are grouped as NMSC. The most common of these, basal cell carcinoma, squamous cell carcinoma and actinic keratoses as carcinomas in situ, are increasingly called keratinocyte carcinoma. Today, the pathogenesis and risk factors of NMSC are relatively well understood, which has led to multiple treatment options, the recognition of NMSC as an occupational disease in Germany and a variety of prevention approaches. Although there is largely general consensus in the dermatological world, knowledge of affected high-risk groups in NMSC and prevention is still very low. The development of target group-oriented awareness and prevention campaigns are therefore urgently needed.

Effect of voriconazole on risk of nonmelanoma skin cancer after hematopoietic cell transplantation

Voriconazole has previously been associated with increased risk for cutaneous squamous cell carcinoma (SCC) in solid organ transplant recipients. Less is known about the risk in patients after hematopoietic cell transplantation (HCT). We evaluated the effect of voriconazole on the risk for nonmelanoma skincancer (NMSC), including SCC and basal cell carcionoma, among those who have undergone allogeneic and autologous HCT. In all, 1220 individuals who had undergone allogeneic HCT and 1418 who had undergone autologous HCT were included in a retrospective cohort study. Multivariate analysis included voriconazole exposure and other known risk factors for NMSC. In multivariate analysis, voriconazole use increased the risk for NMSC (hazard ratio, 1.82; 95% confidence interval, 1.13-2.91) among those who had undergone allogeneic HCT, particularly for SCC (hazard ratio, 2.25; 95% confidence interval, 1.30-3.89). Voriconazole use did not appear to confer increased risk for NMSC among those who had undergone autologous HCT. This is a retrospective study. Voriconazole use represents an independent factor that may contribute to increased risk specifically for SCC in the allogeneic HCT population.