No Evidence for Increased Risk of Cutaneous Squamous Cell Carcinoma in Patients With Rheumatoid Arthritis Receiving Etanercept for Up to 5 Years

Cutaneous squamous cell carcinoma (CSCC) is the second most frequent cancer in humans and its incidence continues to rise. Although CSCC usually display a benign clinical behavior, it can be both locally invasive and metastatic. The signaling pathways involved in CSCC development have given rise to targetable molecules in recent decades. In addition, the high mutational burden and increased risk of CSCC in patients under immunosuppression were part of the rationale for developing the immunotherapy for CSCC that has changed the therapeutic landscape. This review focuses on the molecular basis of CSCC and the current biology-based approaches of targeted therapies and immune checkpoint inhibitors. Another purpose of this review is to explore the landscape of drugs that may induce or contribute to the development of CSCC. Beginning with the pathogenetic basis of these drug-induced CSCCs, we move on to consider potential therapeutic opportunities for overcoming this adverse effect.

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The incidence of cutaneous squamous cell carcinoma in patients receiving voriconazole therapy for chronic pulmonary aspergillosis

Naunyn-Schmiedeberg s Archives of Pharmacology ◽

10.1007/s00210-020-01950-x ◽

2020 ◽

Vol 393 (11) ◽

pp. 2233-2237 ◽

Cited By ~ 1

Author(s):

Chris Kosmidis ◽

Anna Mackenzie ◽

Chris Harris ◽

Rola Hashad ◽

Fiona Lynch ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Cox Regression ◽

Cutaneous Squamous Cell Carcinoma ◽

Pulmonary Aspergillosis ◽

Tertiary Referral Centre ◽

Transplant Patients ◽

Increased Risk ◽

Chronic Pulmonary Aspergillosis

Abstract Voriconazole has been associated with cutaneous squamous cell carcinoma (cSCC) in transplant patients but less is known about the risk in less severely immunosuppressed patients. Our aim was to estimate the incidence of cSCC after voriconazole exposure in patients with chronic pulmonary aspergillosis on a background of chronic lung disease. The notes of patients seen at a tertiary referral centre from 2009 to 2019 with chronic pulmonary aspergillosis were reviewed for the diagnosis of cSCC and voriconazole use documented. Among 1111 patients, 668 (60.1%) received voriconazole for longer than 28 days. Twelve patients received a diagnosis of cSCC; nine had used voriconazole. Mean duration of voriconazole use was 36.7 months. The crude incidence rate was 4.88 in 1000 person/years in those who had voriconazole and 2.79 in 1000 patient/years in those who did not receive voriconazole for longer than 28 days. On Cox regression, age (HR 1.09, 95% CI 1.02–1.16, p = 0.01) and male gender (HR 3.97, 95% CI 0.84–18.90, p = 0.082) were associated with cSCC. Voriconazole use was associated with a slightly increased risk, which was not significant (HR 1.35, 95% CI 0.35–5.20, p = 0.659). Voriconazole use beyond 28 days did not lead to a significantly increased risk of cSCC in a large cohort of patients with chronic pulmonary aspergillosis.

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Profiling of microRNAs in actinic keratosis and cutaneous squamous cell carcinoma patients

Archives of Dermatological Research ◽

10.1007/s00403-021-02221-2 ◽

2021 ◽

Author(s):

Aleksandra Dańczak-Pazdrowska ◽

Jakub Pazdrowski ◽

Adriana Polańska ◽

Brittany Basta ◽

Augusto Schneider ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Actinic Keratosis ◽

Early Stage ◽

Cutaneous Squamous Cell Carcinoma ◽

Genetic Profile ◽

Sequencing Analysis ◽

Chronological Aging ◽

Increased Risk

AbstractActinic keratosis (AK) is a common skin lesion often defined as premalignant with more evidence indicating it as early stage of cutaneous squamous cell carcinoma (cSCC). The AK may remain stable, transform towards incisive cSCC or in some cases revert spontaneously. Several different underlying conditions can increase risk of cSCC, however, advanced age represents major risk of AK and its progression towards cSCC indicating increased risk during chronological aging. Importantly, AK and cSCC are characterized by similar genetic profile, which lead researchers to search for novel biomarkers allowing early detection. As skin sampling is often invasive and causes scaring, in the current study, we investigated a novel approach to establish potential blood circulating genetic markers in patients diagnosed with AK and cSCC. Based on clinical diagnosis and dermoscopy, we recruited 13 patients with AK (divided into two groups: the first included patients with no more than three lesions, the second group included patients with at least ten lesions) and two additional individuals diagnosed with cSCC. Deep sequencing analysis of serum circulating miRNAs detected a total of 68 expressed miRNAs. Further analysis indicated 2 regulated miRNAs for AK cohort and 12 miRNAs for cSCC patients, while there were 26 miRNAs differentially regulated between cSCC and AK patients. There was also one commonly regulated miRNA between AK and cSCC patients and ten miRNAs that were regulated in cSCC when compared with both control and AK patients. We did not observe any differences between the AK groups. In conclusion, our analysis detected in circulation some miRNA that were previously recognized as important in AK, cSCC, and other type of skin cancer supporting this approach as potential non-invasive diagnosis of AK and cSCC.

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Family History of Skin Cancer Is Associated With Increased Risk of Cutaneous Squamous Cell Carcinoma

Dermatologic Surgery ◽

10.1097/dss.0000000000000292 ◽

2015 ◽

Vol 41 (4) ◽

pp. 481-486 ◽

Cited By ~ 9

Author(s):

Maryam M. Asgari ◽

E. Margaret Warton ◽

Alice S. Whittemore

Keyword(s):

Squamous Cell Carcinoma ◽

Family History ◽

Skin Cancer ◽

Cell Carcinoma ◽

Squamous Cell ◽

Cutaneous Squamous Cell Carcinoma ◽

Increased Risk ◽

History Of

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Successful use of immunotherapy to treat advanced cutaneous squamous cell carcinoma in recessive dystrophic epidermolysis bullosa

BMJ Case Reports ◽

10.1136/bcr-2020-238966 ◽

2021 ◽

Vol 14 (2) ◽

pp. e238966

Author(s):

Tony Duong ◽

Debra Wong ◽

Alexander Barrett ◽

Harper Price

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Epidermolysis Bullosa ◽

Checkpoint Inhibitors ◽

Cutaneous Squamous Cell Carcinoma ◽

Dystrophic Epidermolysis Bullosa ◽

Mutational Burden ◽

Increased Risk ◽

Recessive Dystrophic Epidermolysis Bullosa

Recessive dystrophic epidermolysis bullosa (RDEB) is a multisystem inherited disorder associated with fragile skin, blister formation and poor wound healing. Patients with RDEB are at significantly increased risk of recurrent and aggressive cutaneous squamous cell carcinoma (cSCC) and because of their disease complexity, conventional therapies may not be possible. Recent advances in cancer immunotherapy have led to the successful use of immune checkpoint inhibitors (ICIs) in melanoma and other malignancies. However, the effects of ICIs in patients with cSCC and RDEB are currently unknown. A 30-year-old woman with RDEB and multiple unresectable cSCCs was found to have high tumour mutational burden and PD-L1 (programmed cell death-ligand 1) expression. She was started on an ICI, which yielded disease control and was well tolerated. Furthermore, her RDEB wounds improved. This case demonstrates successful use of immunotherapy for advanced cSCC in RDEB, a disease that is often challenging to treat with local therapies.

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

Frontiers in Medicine ◽

10.3389/fmed.2021.735585 ◽

2021 ◽

Vol 8 ◽

Author(s):

Dana E. Rollison ◽

Jane L. Messina ◽

Basil S. Cherpelis ◽

Neil A. Fenske ◽

Michael J. Schell ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

T Cells ◽

Regulatory T Cells ◽

Cell Carcinoma ◽

Squamous Cell ◽

Cutaneous Squamous Cell Carcinoma ◽

Skin Damage ◽

Cancer Screenings ◽

Increased Risk ◽

Ultraviolet Radiation Exposure

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

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