Squamous Cell Carcinoma And Immunosuppression Risks
This study aimed to compare the clinical characteristics and outcomes of cutaneous squamous cell carcinoma (cSCC) in immunosuppressed and immunocompetent patients. The retrospective analysis included 935 cSCC cases, with 19.5% of the patients being immunosuppressed. The study revealed several notable findings:
- Immunosuppressed patients with cutaneous squamous cell carcinoma tend to be younger (69.3 years old) compared to immunocompetent patients (74.8 years old).
- There was a higher proportion of males among immunosuppressed patients (78.6%) compared to immunocompetent patients (67.2%).
- Immunocompromised patients presented with higher-grade cutaneous squamous cell carcinoma tumors, characterized by moderate or poor differentiation (25.7% and 9.2%, respectively), whereas immunocompetent patients had lower rates of moderate or poor differentiation (15.8% and 7.2%, respectively).
- However, no significant differences were observed in other tumor characteristics, such as clinical tumor dimensions, Brigham and Women’s Hospital tumor staging, or cumulative risk of metastasis and recurrence.
- Immunosuppressed patients faced an increased risk of disease-specific death, with a hazard ratio (HR) of 2.05.
- The overall survival rate in immunosuppressed patients was worse, with an adjusted HR of 1.83. Notably, solid organ transplant recipients had the lowest overall survival rate among immunosuppressed patients, with an HR of 1.62.
In conclusion, this study demonstrated that immunosuppressed patients with cSCC differ in age, gender distribution, and tumor grade compared to immunocompetent patients. Immunocompromised patients faced a higher risk of disease-specific death and had poorer overall survival, especially among solid organ transplant recipients. These findings can help guide clinical management strategies for cSCC in immunosuppressed individuals.
The study findings indicate that immunosuppressed individuals are more likely to develop poorly differentiated cSCC tumors and experience reduced overall and cSCC-specific survival rates. Notably, existing staging systems for cSCC do not account for the influence of immunosuppression as a risk factor. Therefore, considering a patient’s immune status in these staging systems could be advantageous in improving the accuracy of risk assessment for cutaneous squamous cell carcinoma. This may lead to more precise risk stratification and ultimately enhance clinical management strategies for cSCC.
Cutaneous squamous cell carcinoma (cSCC) is a prevalent nonmelanoma skin cancer, with a substantial annual incidence of about 1.8 million cases seen in America. While it often goes under the radar in comparison to melanoma, the number of annual cSCC-related deaths is similarly significant. Various risk factors contribute to cSCC, including age, exposure to ultraviolet light (UV), male gender, a history of skin cancers, and immunosuppression.
Studies on cSCC in immunosuppressed individuals have revealed striking disparities when compared to the general population. These disparities encompass significantly higher incidence rates (up to 100-fold), an elevated risk of metastasis (ranging from 4% to 8%), and a notably increased likelihood of cSCC-related mortality (reaching 30.5%). The immunosuppressed group most extensively studied comprises solid organ transplant recipients (SOTRs). SOTRs tend to develop more aggressive cSCC tumors that are characterized by their larger size, poor differentiation, deep infiltration, and a higher incidence of perineural or lymphovascular invasion. Additionally, these tumors often occur in high-risk areas like the lip or ear. Specific immunosuppressive medications, such as azathioprine and cyclosporine, have been associated with the development of more aggressive cSCCs.
Given the need for a comprehensive understanding of clinical and histologic features, as well as outcomes in the immunosuppressed population, this study aims to examine the connections between immune status and cutaneous squamous cell carcinoma tumor characteristics. It also explores disease-related outcomes, including metastasis, recurrence, cSCC disease-specific death (DSD), and overall survival (OS). Furthermore, the study stratifies its analysis based on the type of immunosuppression to assess potential differences linked to the underlying cause of immunosuppression.
This study, approved by the Mayo Clinic Institutional Review Board, involved a comprehensive analysis of 935 cases of cutaneous squamous cell carcinoma (cSCC). These cases were selected from two distinct databases: the high-risk cutaneous squamous cell carcinoma database and the normal-risk cSCC database, which collectively contained approximately 2,800 cases identified between 1999 and 2016 across Mayo Clinic locations in Jacksonville, Florida, Rochester, Minnesota, and Scottsdale, Arizona.
The cases were identified through an extensive, enterprise-wide search, relying on histopathologic diagnoses of cutaneous squamous cell carcinoma found in archived specimens’ pathology reports. The high-risk database encompassed around 400 cases of tumors staged as BWH T2a or higher, including those linked to poor outcomes such as recurrence, metastasis, and disease-specific death (DSD). The normal-risk database, on the other hand, comprised a randomized sampling of 2,400 patients with biopsy-proven cSCC. This sampling accurately represented the average Mayo Clinic patient from the broader cohort, with stratification based on age, gender, and race.
Clinical data, including information on age, gender, and immunosuppression status, were extracted from electronic medical records. Patients were categorized as immunosuppressed if they had documented immunosuppression status before their initial cSCC diagnosis, while immunocompetent patients had no documented immunosuppression status both before their initial diagnosis and through their last follow-up.
The study included cases with adequate tissue for review, available data regarding immunosuppression status, Brigham and Women’s Hospital (BWH) and American Joint Committee on Cancer (AJCC) tumor staging, and a follow-up period of at least 18 months. This follow-up was essential for documenting outcome data, encompassing local and nodal recurrence, regional metastasis (in-transit and nodal), distant metastasis, and disease-associated mortality.
To ensure the accuracy of the findings, all cases underwent a meticulous histopathologic re-review by board-certified dermatopathologists, who confirmed tumor characteristics and staging. Notably, the study utilized the best available tissue samples, with 77.2% originating from initial biopsies and 22.8% from subsequent tumor excision pathology.
Patient demographics and tumor characteristics were thoroughly analyzed in this study. These analyses involved comparisons between immunosuppressed and immunocompetent cohorts, as well as categorization by specific types of immunosuppression. Various statistical tests, including Kruskal-Wallis, analysis of variance, and chi-square tests, were appropriately applied to facilitate these comparisons.
Recurrence, both local and nodal, metastasis, encompassing in-transit and distant cases, and disease-specific death (DSD) were estimated using the Fine-Gray method. This method considers competing risk events, such as death before the event of interest, to provide accurate estimates. Comparisons between these outcomes and clinical variables of interest, including immunosuppression status, were conducted using the Gray k-sample test.
To assess overall survival (OS), the Kaplan-Meier method was employed. Differences in OS were evaluated using the Log rank test. Additionally, the study utilized univariate and multivariable Cox Proportional Hazard models to estimate the risk of cSCC-specific death and OS. The multivariable models were adjusted for age, gender, and tumor differentiation to enhance the accuracy of the findings.
In this analysis, a p-value of less than 0.05 was considered statistically significant. All statistical analytical processes were done with SAS v9.4 (SAS Institute), ensuring rigor and reliability in the study’s results.
This study encompassed a cohort of 935 patients, among which 69.4% were male, and 19.5% were classified as immunosuppressed individuals. The majority of patients were of Caucasian descent (92.9%), with smaller percentages representing other ethnic backgrounds.
Immunosuppressed patients exhibited distinctive characteristics. They were notably younger at the time of cSCC diagnosis (69.3 vs. 74.8, p < 0.001) and had a higher proportion of males (78.6% vs. 67.2%, p = 0.003). These patients had various reasons for immunosuppression, with solid organ transplant accounting for 54.9%, autoimmune disease for 14.8%, hematologic malignancy for 14.8%, solid organ malignancy for 3.8%, and stem cell transplant for 1.6%.
Regarding tumor characteristics, immunosuppressed patients exhibited a higher prevalence of moderately or poorly differentiated tumors (25.7% vs. 15.8%, p = 0.009; 9.2% vs. 7.2%, p = 0.009, respectively). Nevertheless, there were no significant disparities in Brigham and Women’s Hospital (BWH) staging between the immunosuppressed and immunocompetent groups.
The study’s outcomes revealed that immunosuppression had no significant impact on the rates of tumor recurrence, cumulative metastasis, or metastasis incidence between immunocompetent and immunosuppressed individuals. However, overall survival (OS) was notably worse in the immunosuppressed population, with a hazard ratio (HR) of 1.83 [95% confidence interval, CI: 1.42–2.35], p < 0.001. This finding remained consistent even after adjusting for age, gender, and tumor differentiation, with an adjusted HR of 2.48 [95% CI: 1.84–3.35], p < 0.001.
Concerning disease-specific death (DSD), univariate analysis revealed that immunosuppressed patients had a higher risk compared to immunocompetent individuals (HR [95% CI: 2.05 [1.13–3.74], p = 0.0128). After adjusting for age, gender, and tumor differentiation, there was a trend towards increased DSD in immunosuppressed patients, although this did not reach statistical significance (adjusted HR [95% CI: 1.89 [0.90–3.99], p = 0.095).
The study also stratified immunosuppressed patients by the cause of immunosuppression. Solid organ transplant recipients (SOTRs) displayed the highest rates of DSD (HR [95% CI: 2.84 [1.47–5.50], p = 0.0045) and the lowest OS (HR [95% CI: 1.62 [1.17–2.24], p < 0.0001) compared to both immunocompetent individuals and non-SOTR immunosuppressed patients. These findings provide valuable insights into the clinical management of immunosuppressed individuals with cSCC.
This study provides a comprehensive comparison of cutaneous squamous cell carcinoma (cSCC) tumor characteristics and disease-related outcomes, shedding light on the clinical management of immunosuppressed patients. It aligns with previous findings by revealing that individuals with immunosuppression, particularly solid organ transplant recipients (SOTRs), are more likely to be males and are diagnosed with cSCC at a younger age compared to their immunocompetent counterparts.
Immunosuppressed patients presented with tumors that exhibited higher rates of moderate or poor differentiation, reaching 34.9% compared to 23.0% in immunocompetent patients. Notably, poor differentiation, a tumor characteristic, emerged as an independent risk factor for both disease-specific death (DSD) and reduced overall survival (OS).
The existing literature has shown some inconsistencies concerning tumor characteristics and outcomes in cutaneous squamous cell carcinoma patients with immunosuppression. While some studies have reported less differentiated and more deeply infiltrative tumors in immunosuppressed cohorts, others did not observe significant differences in tumor depth or differentiation.
Furthermore, previous research has produced mixed findings on the impact of immunosuppression on outcomes such as OS, DSD, and metastasis. While some studies indicated a significant association between immunosuppression and adverse outcomes, others failed to establish such a connection. This study contributed to the body of knowledge by revealing a lower OS in immunosuppressed patients, with an adjusted hazard ratio of 2.48 [95% CI: 1.84–3.35], though no significant disparities were observed in the rates of tumor recurrence or metastasis compared to immunocompetent patients. Immunocompromised individuals exhibited a twofold increase in the risk of DSD without adjustment. SOTRs, in particular, faced the highest risk of DSD within the stratified immunosuppressed groups.
The diverse array of iatrogenic and disease-induced immunosuppression and the complex interplay between these factors contribute to the variability in disease susceptibility and outcomes. The lack of standardized definitions and subgroup stratifications for immunosuppressed populations may contribute to the inconclusive nature of the findings across studies.
This study highlights the need for further research into specific immunosuppressed subgroups to better understand their risk of adverse outcomes in cSCC. The study underscores the potential benefits of incorporating immune status and considering the etiology of immunosuppression in cutaneous squamous cell carcinoma risk stratification. Additionally, exploring the molecular profiles of tumors in immunosuppressed patients may unveil genomic biomarkers that predict outcomes within this unique population.
In summary, this retrospective cohort study involving 935 cutaneous squamous cell carcinoma patients revealed that immunosuppression correlated with a younger age at diagnosis, male gender, and higher-grade tumors. Furthermore, immunocompromised status was linked to an elevated risk of DSD and reduced OS. Among these immunosuppressed patients, SOTRs experienced the most unfavorable outcomes, characterized by the highest DSD rates and the lowest OS.
Oncology Related Tools
- Prognostic Scoring for Myelofibrosis
- Opioid Conversion Calculator
- Updated Advanced Opioid Conversion Calculator
- Nonsteroidal anti-inflammatory drugs (NSAID) Selection Tool
- Absolute Neutrophil Count Calculator
- Body Surface Area (BSA) Multi-Calc
- Carboplatin AUC Calculator
- Carboplatin AUC – Updated Version
- Urinary Indices, Renal Failure Index (RFI) and Fractional Excretion of Sodium (FE-NA)
- Creatinine Clearance (CRCL) – Standard Calculator
- Creatinine Clearance Multi-Calc – All of the latest research
- Patient Controlled Analgesia (PCA) Settings
- Intravenous Antineoplastic Agents – Administration Guidelines
- Therapeutic Drug Levels
- Beers Criteria for potentially inappropriate medications
- Allergic response? 12-step desensitization protocol
- Protein requirements calculator
- Basal Metabolic Rate (BMR) Multi-calc (Estimate caloric requirements)
- Irritable Bowel Syndrome Treatment Options
- Common Anti-emetics
- Fall Assessment – Berg Balance Scale
- Topical Steroids Potency Selection Tool
- Necrotizing Fasciitis Treatment And Bacterial Isolates Mortality Risk
- Acellular Dermal Matrix (ADM) For Burn And Trauma Wounds
- Visceral Adiposity And Heart Failure Risk
- Psoriasis Risk In Children With High BMI
- Traumatic Scalp Defects: Case Studies And Treatment Approaches
- Perforator Flaps For Patellar Defects
- GERD And Risk Factors Of Age And Obesity
- Cataract Repair: 20-Year Outcomes In Diabetic Patients
- Spitz Lesions: Clinical Outcomes
- Obesity Treatment With Tirzepatide And Semaglutide
- Hydroxyurea: Pediatric Use In Sickle Cell Anemia
- AKI In Alcohol-Related Hepatitis
- Biologic Therapy Tapering In Inflammatory Arthritis
- Rheumatoid Arthritis: Monitoring Disease With Neutrophil-To-Monocyte Ratio
- Cefuroxime Prophylaxis For Cataract Postoperative Endophthalmitis
- HIV Treatment And Long-Acting Therapy Preferences
- Idiopathic Parkinson’s Tremors: Treatment Options
- Ganaxolone Treatment For Refractory Epilepsy
- Bipolar Disorder And The Impact Of Insulin Sensitivity
- Blue Light Therapy For Melasma Patients
- Insulin Sensitivity In The Brain And Periphery
- Cabozantinib Therapy In Hepatocellular Carcinoma
- Obese Children And Related Skin Conditions
- PD-1/L1 Inhibitors: Treatment Efficacy In Urothelial Carcinoma
- Skin Lightening: Topical Approaches To Treatment
- PPE And Skin Related Reactions
- Encapsulated Papillary Carcinoma Membrane Characteristics
- Ibrutinib Treatment In Waldenström Macroglobulinemia
- Eyelid Carcinoma (SGC): A Tool To Predict Recurrence
- Stomach Cancer: A Meta-Analysis Of Robotic Surgery Complications
- Cognitive Behavioral Therapy In Patients With Insomnia And Chronic Fatigue
- Chemotherapy-Induced Thrombocytopenia In Nasopharyngeal Carcinoma
- Endocrine Therapy Outcomes In Senior Breast Cancer Patients
- Hepatocellular Treatment Outcomes: The Influence Of Butyrate Producers
- Non-Invasive Breast Carcinoma Treatment Outcomes
- Control Of Allergic Rhinitis And Asthma Test: A COSMIN Analysis
- Pilonidal Sinus Disease And Carcinoma Prevalence
- Sintilimab And Docetaxel Treatment Comparison In Advanced Lung Cancer
- Tislelizumab Treatment And Quality Of Life In Lung Cancer Patients
- Ciclopirox Hydrolacquer Therapy For Adult Onychomycosis
- Allergic Rhinitis And Genetic Risk Factors
- Serum Potassium Levels And Mortality Risk In CKD
- Postoperative Delirium In The NICU: Hormonal Risk Factors
- Onychomycosis And Diabetic Foot Syndrome
- Childhood BMI And Allergies: A Comprehensive Review
- Pediatric Onychomycosis Prevalence: A Systemic Review
- Hormone Disturbances In Migraine Disorder: A Meta-Analysis
- IGF-1 Levels In Pediatric Low-Level Gliomas
- Visual Field Defects In Patients With Pituitary Tumors
- Chronic Spontaneous Urticaria: Studying Age-Specific Therapies
- Levothyroxine Treatment In Patients With Thyroid Cancer
- Ocular Surgery In Infants And Post-Op Eye Drop Risks
- Cancer Care: Gender Bias In Decision-Making
- Respiratory Syncytial Virus Infection: A Tool For Assessing Clinical Severity
- Gynecologic Cancer Survivors: A Study Of Lifestyle Factors
- Non-Hodgkin Lymphoma Survivors: Secondary Malignancy Risk
- Antithyroid Drug Therapy And Cardiovascular Morbidity
- Eosinophilic Dermatosis In Hematological Malignancy (EDHM): Case Study Reports
- Uterine Leiomyosarcoma: A-Meta Analysis Of Systemic Therapy Effectiveness
- Off-Label Medication Use In Oncology
- Monocytosis And Patient Risk Of Malignancy And Mortality
- Bedside Pediatric Early Warning System: A Validation Study
- Chronic Hyponatremia In Heart Failure
- Massage Therapy For Oncology Patient Pain
- Eyelid Rhabdomyosarcoma Survival In Children’s Oncology
- Injured Athletes: A Meta-Analysis Comparing Topical And Oral Analgesic Efficacy
- Acute Myeloid Leukemia And Diverse Patient Survival Outcomes
- Sarcopenia And Chronic Kidney Disease
- Childhood Obesity: Targeted Dietary Interventions
- Supragastric Belching And Acid Reflux Severity
- Diabetic Peripheral Neuropathy Diagnosis Using Nerve Ultrasonography
- IBD: A Link To Cancer And Infection
- Renal Transplant Risks With Prostate Cancer
- COPD Risk With Diabetes And Pre-Diabetes
- Urothelial Carcinoma – Uretal And Renal Pelvic Tumors
- Merkel Cell Carcinoma: A Case Of Metastasis To The Tonsils
- Infant Formula Protein Content And Childhood Obesity
- Maternal Migraines And Associated Pediatric Cancers
- Pediatric Neuroblastoma Diagnosis Using Urinary Catecholamine Metabolites
- Finerenone Therapy In CKD And Type 2 Diabetes
- Binge Eating Habits And Diabetic Implications
- Pain Intensity In Idiopathic Inflammatory Myopathies And Rheumatic Diseases
- Melanoma Diagnosis Without Biopsy
- Pediatric Opioids And Pain Control In Fractures
- Daikenchuto Treatment For Chronic Constipation
- Prenatal Gingivitis Prevalence In A Clinical Trial Exploring Oral Hygiene Education
- Autistic Adults: A Study On Cognitive Therapy Experiences
- The Impact Of Long-Term Opioid Treatment On Endocrine Parameters
- Skeletal Muscle Index And Ovarian Cancer Prognosis: A Meta-Analysis
- Diabetes Mellitus During The Pandemic
- Carfilzomib Therapy In Pediatric Acute Lymphoblastic Leukemia
- Golimumab Compliance In Long-Term Arthritis Treatment
- Medullary Thyroid Cancer And Vocal Cord Paralysis
- Primary Adenocarcinoma Of The Orbit: A Case Study
- Survival Trends: Pancreatic Cancer in the USA
- Nusinersen Therapy For Pediatric Spinal Muscular Atrophy
- Pediatric Liver Transplantation: A New Biological Abdominal Wall
- Influenza Surveillance: A Review Of Data Sources
- Remission of Renal Cell Carcinoma With Brain Metastases: A Case Study
- Dry Eye Disease And Dehydration
- Macular Edema Therapy Using Dexamethasone Nanoparticle Suspension
- Colorectal Cancer Screening For Older Adults
- Satiation And Satiety: An Overview And Clinical Calculator
- Cholesterol Screening To Aid In Glaucoma Detection
- Hearing Screening After Chemotherapy: A Study On Childhood Cancer Survivors
- Olfactory Dysfunction and Screening For Depression: A QOL Study
- Cancer Diagnosis And Mental Health
- Mental Health Screening In Psoriatic Arthritis Patients
- Prostate Cancer: A New Biopsy Risk Calculator Using MRI
- Mental Health Study in Cancer Survivors
- Mental Health Screening In The Community
- Bone Mineral Density Screening Combined With Mammography
- Bone Mineral Density In Type 1 Diabetes Mellitus
- Cochlear Implants and Vestibular Screening
- Aprocitentan In Resistant Hypertension
- Predicting Cardiovascular Disease With Body Mass Index
- Obesity Screening To Predict Hot Flashes
- Hypertension Screening For Cardiovascular Health
- Dental Screening For Cardiovascular Disease Risk
- Blood Pressure and CVD Risk Reduction
- Lifestyle Changes For Hypoglycemia Prevention
- Ovarian Adenocarcinoma With Glaucoma: A Case Report
- Community Hypertension and Atherosclerosis Risk
- Thyroid Malignancy and Serum Calcitonin
- Rare Schwannoma In Lateral Nasal Wall
- Pyrotinib Therapy In HER2+ Breast Cancer
- Osteopenia Predicts Outcomes in Pancreatic Cancer
- Outcomes of Physical Exercise Regimens in Advanced Cancer
- Penile Squamous Cell Carcinoma And HPV
- Radiation Therapy And VTE Risk
- Pseudouveitis With Pancreatic Carcinoma: A Case Study
- Cancer Prevention In Rural Communities
- Skeletal Muscle Mass and Cancer Patient Quality of Life: A Meta-Analysis
- Incidence of Secondary Cancers After CIRT VS RT
- Filanesib Combination Therapy in Multiple Myeloma
- Pediatric Leukemia Patients Utilizing Levofloxacin
- Breast Cancer And An Analysis Of Cardiovascular Events
- Monotherapy Or Chemotherapy Adjunct: Pembrolizumab in Advanced NSCLC
- Advanced Gastric Cancer: Prognosis with Nivolumab Monotherapy
- Sinonasal B‐Cell Lymphomas A Cohort Study On Progression And Recurrence
- Platinum Resistant Recurrent Ovarian Cancer Treatment+/-Bevacizumab
- Metastatic Melanoma and Follow-Up MRI Scans
- Isatuximab Treatment in Refractory T-Acute Lymphoblastic Leukemia
- Ocular Melanoma and Treatment with Metformin
- Gastric Neuroendocrine Neoplasms
- Lung Cancer with Brain Metastasis After Late-Onset Bipolar Disorder: Case Report
- Anlotinib with Camrelizumab in Lung Cancer Treatment
- Sebaceous Carcinoma Treatment Outcomes: A Multicenter Study
- Diffuse-Type Tenosynovial Giant Cell Tumors: Treatment and Progression
- Lung Spindle Cell Carcinoma Responsive to Pembrolizumab: A Rare Case Report
- DNA Methylation Profiling in Sarcoma Classification
- Breast Tomosynthesis Simulator For Virtual Clinical Trials
- Renal Cell Carcinoma-Prognosis Via Albumin Levels
- Diagnostic Error Causing Cases of Cytopenia
- Hodgkin’s Lymphoma: A Case Study With Nystagmus and Diplopia
- Brugada Syndrome Treated with Lenalidomide: A Case Study
- Koolen-de Vries Case Study
- Suicidal Ideation and Somatic Treatments
- Study on Pavlovian Fear Conditioning and Fear Reversal in OCD
- Anxiety Scales in Lewy Body Disease
- Inoperable Locally Advanced Non-Small Cell Lung Cancer: Survival Rates of Endostar, CCRT
- Physician Practice Management and Private Equity
- Physician Spending And Its Association With Patient Outcomes
- Physician Burnout: Causes and Prevention
- LEAP-MS: Adaptations for Advanced Stages
- MS: Exercise Impacts on MRI
- The Role of Preretirement Job Complexity in Cognitive Performance
- Extrapontine Myelinolysis and PTA in Pregnancy
- Verbal Communication and Masks
- Sugammadex Versus Neostigmine in Thyroidectomy
- SGLT Inhibitors on Weight and Lipid Metabolism in Diabetes
- Saxagliptin: Obese Patients with Impaired Glucose Tolerance
- Levothyroxine Therapy and Depression
- Grave’s Disease and Risk of Systemic Lupus Erythematosus
- Benign Thyroid Removal and Patient Satisfaction
- MF- Biology, Management, and a Case Study of Ocular Manifestation
- Quality Of Life In Adolescent Cancer Survivors
- Cancer Opioid Risk Score
- Oncology-Specific Opioid Risk Calculator In Cancer Survivors
- 3D MRI for Non-invasive Ocular Proton Therapy of Uveal Melanomas
- Sexual Dysfunction in Prostate Cancer Patients
- 3-Day Surprise Question To Predict Survival Rates in Advanced Cancer Patients