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

Abstract

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.

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

“…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 ].…”

“…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.…”

Risk Factors and Innovations in Risk Assessment for Melanoma, Basal Cell Carcinoma, and Squamous Cell Carcinoma

“…Immunosuppression is a medical condition strongly linked to cSCC development. Immunocompromised patients are significantly younger at the time of cSCC diagnosis, compared with non-immunocompromised cSCC patients (68 vs. 78 years), display higher recurrence rates (24% vs. 15%) and have more often multiple cSCCs (28% vs. 10%) [ 117 ]. The association between immunosuppression and cSCC risk was reported for several underlying conditions like chronic lymphocytic leukemia (4.82 fold increased cSCC risk) or HIV (5.40 fold increased cSCC risk), but it is especially strong for solid organ transplant recipients (OTR) [ 67 , 118 ].…”

PTCH1 Gene Variants, mRNA Expression, and Bioinformatics Insights in Mexican Cutaneous Squamous Cell Carcinoma Patients

“…Non-melanoma skin cancer (NMSC) stands as one of the most prevalent forms of cancer globally, with cutaneous squamous cell carcinoma (cSCC) accounting for approximately 20% of all NMSC cases, placing it as the second most common type of epithelial malignancy. The incidence of skin cancers continues to increase, and it is well-known that chronic exposure to UV radiation (UVR) from sunlight is the main risk factor [ 1 , 2 ]. cSCC arises from epidermal keratinocytes, and non-UVR risk factors such as older age, fair skin, immunosuppression, and exogenous chemical mutagens are relevant in its development [ 3 , 4 , 5 ].…”