Risk factors and prevention strategies for cutaneous squamous cell carcinoma in transplant recipients

Urso, Brittany; Kelsey, Andrew; Bordelon, Jenna R.; Sheiner, Patricia A.; Finch, Justin; Cohen, Joel L.

doi:10.1111/ijd.16070

Cited by 7 publications

(7 citation statements)

References 43 publications

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“…Immunosuppression is strongly associated with an increased risk for cSCC. This association was reported by many researchers who focused on solid organ transplant recipients (SOTR) [ 8 , 9 ]. Other medical causes for immunosuppression were previously reported to be associated with cSCC.…”

Section: Introductionmentioning

confidence: 69%

Cutaneous Squamous Cell Carcinoma in Immunocompromised Patients—A Comparison between Different Immunomodulating Conditions

Zavdy

Coreanu

Bar-On

et al. 2023

Cancers

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Background: Immunosuppression is strongly associated with an increased risk of developing cutaneous squamous cell carcinoma (cSCC). Studies on solid organ transplant recipients (SOTR) and chronic lymphocytic leukemia (CLL) patients have already demonstrated higher rates of aggressive cSCC tumors in these populations compared to immunocompetent controls. Studies on other immunosuppressed patient groups are scarce. This study was aimed at assessing the effects of different immunomodulating conditions on patients diagnosed with cSCC. We sought to compare the clinical features, treatments, and survival rates among the different study groups, as well as outcomes to those of immunocompetent controls with cSCC. Methods: A retrospective analysis of 465 cSCC patients, both immunosuppressed (IS) and immunocompetent controls. Etiologies for immunosuppression included SOTR, CLL, chronic kidney disease (CKD), psoriasis, rheumatoid arthritis (RA) and systemic lupus erythematous (SLE). Results: Compared to the control group, IS patients demonstrated several significant differences. These include higher rates of positive resection margins, higher recurrence rates, and multiple SCC tumors. Patients in the IS group, who were also given immunomodulating agents, demonstrated even lower survival rates. Cox regression analysis demonstrated statistically significant decreased overall survival (OS) rates for IS patients compared to the controls (OR = 1.9, p = 0.031). SOTR patients tend to have multiple cSCC tumors (35%), with the highest number of primary tumors compared to controls (2.54 tumors per patient on average, p < 0.001), but also compared to all other IS groups. The average SCC lesion size in the SOTR group was the smallest, measuring at 13.5 mm, compared to the control group and all other IS groups. Decreased survival rates were seen on Cox regression analysis compared to controls (HR = 2.4, p = 0.001), but also to all other IS groups. CLL patients also had the highest rates of positive margins compared to controls (36% vs. 9%, p < 0.01) and to all other IS groups. They were also most likely to get adjuvant or definitive oncological treatments, either radiotherapy or chemotherapy, compared to controls (36% vs. 15%, p = 0.02) and to other IS groups. Patients in the CKD group demonstrated the highest rates for multiple cSCC (OR = 4.7, p = 0.001) and the worst rates of survival on Cox regression analysis (HR = 3.2, p = 0.001). Both rheumatoid arthritis and psoriasis patients demonstrated the shortest disease-free survival rates (2.9y ± 1.1, 2.3y ± 0.7, respectively), compared to controls (4.1y ± 2.8) and to all other IS groups. Conclusions: Among cSCC patients, immunosuppression due to SOTR, CLL, CKD, RA, and psoriasis is associated with worse outcomes compared to controls and other IS groups. These patients should be regarded as high-risk for developing aggressive cSCC tumors. This study is the first to assess and compare cSCC outcomes among multiple IS patient groups.

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Section: Introductionmentioning

confidence: 69%

Cutaneous Squamous Cell Carcinoma in Immunocompromised Patients—A Comparison between Different Immunomodulating Conditions

Zavdy

Coreanu

Bar-On

et al. 2023

Cancers

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Section: Resultsmentioning

confidence: 99%

“…The coexistence of impaired T cell immunity, β-HPV infection, and carcinogen exposure (such as UVB irradiation and DMBA) or chronic trauma promote cSCC initiation ( Figure 2 ). An impaired T cell immunity exists in certain populations, such as organ transplant recipients on chronic immunosuppression, atypical epidermodysplasia verruciformis (EV), and EV-like phenotypes [ 10 , 11 , 12 , 13 , 33 , 34 , 35 ]. Consequently, these individuals possess markedly weakened anti-β-HPV defences, which are primarily orchestrated by T cells.…”

Section: Discussionmentioning

confidence: 99%

“…However, several studies have reported increased β-HPV replication in the skin and greater β-HPV seropositivity in cSCC patients, which suggest a potential role for viral oncogenesis [18]. More importantly, the increased incidence of cSCC with concomitantly higher rates of β-HPV amongst solid organ transplants suggests a role for anti-β-HPV immunity in carcinogenesis [10][11][12][13]. Borgogna et al (2023) and Antsiferova et al (2017) utilised transgenic mice that express early region genes (encoding E1, E2, E4, E6, and E7) of HPV8, the prototypical β-HPV that is studied in HPV-related cSCC [19][20][21].…”

Section: T Cell Immunity In β-Hpv-related Epithelial Carcinogenesismentioning

confidence: 99%

“…Immunosuppression profoundly elevates the risk of cancers associated with viral infection, including cSCC. Immunosuppressed patients have up to 100-fold higher cSCC rates compared with the general population [ 10 , 11 , 12 , 13 ]. Antiviral immunity is chiefly regulated by the adaptive immune system, where T cells orchestrate effective long-lived responses.…”

Section: Introductionmentioning

confidence: 99%

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T Cell Immunity in Human Papillomavirus-Related Cutaneous Squamous Cell Carcinoma—A Systematic Review

Tay,

2024

Diagnostics

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Cutaneous squamous cell carcinoma (cSCC) is an invasive malignancy that disproportionately afflicts immunosuppressed individuals. The close associations of cSCC with immunosuppression and human papillomavirus (HPV) infection beget the question of how these three entities are intertwined in carcinogenesis. By exploring the role of T cell immunity in HPV-related cSCC based on the existing literature, we found that the loss of T cell immunity in the background of β-HPV infection promotes cSCC initiation following exposure to environmental carcinogens or chronic trauma. This highlights the potential of developing T-cell centred therapeutic and preventive strategies for populations with increased cSCC risk.

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Rechallenge and retreatment with topical imiquimod 5% in transplant recipients: A multicenter experience on actinic keratoses and basal cell carcinomas

Fava,

Roccuzzo,

Macagno

et al. 2024

JEADV Clinical Practice

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BackgroundSolid organ transplant recipients (SOTRs) have an increased risk of developing non melanoma skin cancers (NMSCs). The use of Imiquimod, a toll‐like‐receptor agonist, is still debated in SOTRs.ObjectivesThe aim of this study was to evaluate efficacy and safety of topical Imiquimod in two Dermatology Centres for skin cancers in SOTRs.MethodsAll SOTRs with age > 18 and a dermoscopic diagnosis of superficial basal cell carcinoma (BCC) and/or actinic keratose (AK), annually followed up between January 2022 and December 2022 were screened.Results80 NMSCs (41 BCC and 39 AK) in 66 SOTRs were identified and treated.57 (86.4%) were male. The mean age was 66.2 years (30−85). 60 patients (90.1%) had transplanted kidney, 1 (1.5%) lung, 3 (4.5%) liver, and 1 (1.5%) heart.The average time since first transplant was 17 years (3−40 years). Tacrolimus, steroids, and mycophenolate mofetil were the most frequently used immunosuppressants (71%; 67.7%; 53.2% of cases, respectively).Responses to the first course of treatment were CR in 64.3% of cases (53.6% in AK; 67.7% in BCC); PR in 28.6% of cases (42.9% in AK; 12.9% in BCC); NR in 12.5% of cases (3.6% in AK; 19.4% in BCC). Fourteen patients received a second course of imiquimod for a persistent lesion (1 AK, 4 BCC) or a new lesion (4 AK, 5 BCC).Responses to the second course of treatment were observed in 4 (80%) and 7 (78%) cases in the persistent and new lesion, respectively (p = 0.34).No systemic adverse events were noted. The main side effects were mild: erythema, scales, and crusts, itching, or pain.ConclusionsTopical imiquimod represents a viable and safe option in this category of patients.The response to imiquimod in subjects who have had more than one cycle is not related to the response to previous treatments but rather to the intrinsic characteristics of the lesion.

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Risk factors and prevention strategies for cutaneous squamous cell carcinoma in transplant recipients

Cited by 7 publications

References 43 publications

Cutaneous Squamous Cell Carcinoma in Immunocompromised Patients—A Comparison between Different Immunomodulating Conditions

Cutaneous Squamous Cell Carcinoma in Immunocompromised Patients—A Comparison between Different Immunomodulating Conditions

T Cell Immunity in Human Papillomavirus-Related Cutaneous Squamous Cell Carcinoma—A Systematic Review

Rechallenge and retreatment with topical imiquimod 5% in transplant recipients: A multicenter experience on actinic keratoses and basal cell carcinomas

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