Global burden and prediction study of cutaneous squamous cell carcinoma from 1990 to 2030: A systematic analysis and comparison with China.

Background: China has the highest number of new cancer cases and deaths globally. Due to particularly low scores in health care quality for cutaneous squamous cell carcinoma (cSCC), the country's cSCC burden requires greater awareness. Consequently, we aimed to evaluate and predict the trend of the cSCC burden globally and in China from 1990 to 2030. Methods: We retrieved data from the Global Burden of Disease 2019 study, which provided estimates of the incidence, mortality, prevalence, and disability-adjusted life years (DALYs) of cSCC from 1990 to 2019. We set up joint-point analyses and Bayesian age-period-cohort (BAPC) models to predict the disease burden of cSCC up to 2030. Results: In 2019, China reported age-standardised rates of cSCC prevalence, incidence, mortality, and DALYs of 2.54, 2.12, 0.88, and 16.76 per 100 000 population, respectively. The country's prevalence and incidence rates from 1990 to 2019 were lower than the global levels, but its mortality and DALY rates were higher. The age-standardised rates were higher for males, and the disease burden increased with each age group globally and in China. Moreover, the average annual percentage change showed all indicators were growing faster than the global levels. According to the BAPC model, there will be an upward trend in the prevalence and incidence globally and in China between 2020 and 2030, with a decrease in mortality and DALYs. Conclusions: We observed an upward trend in the cSCC burden over the past 30 years in China. Prevalence and incidence are expected to continue at a higher rate than the global average in the next decade, while mortality and DALYs are predicted to decrease. As the Chinese population ages, efforts toward managing and preventing cSCC should be targeted towards the elderly population.

Causality Assessment Between Idiopathic Inflammatory Myopathies and Lung Cancer: A Bidirectional 2-Sample Mendelian Randomization.

BACKGROUND: Although observational studies have revealed associations between idiopathic inflammatory myopathies (IIMs) and lung cancer (LC), they have not established a causal relationship between these 2 conditions. METHODS: We used a 2-sample Mendelian randomization approach to examine the bidirectional causal associations between IIMs and LC, using single-nucleotide polymorphisms selected from high-quality genome-wide association studies in the FinnGen database. Sensitivity analyses were conducted to assess potential heterogeneity and pleiotropy impacts on the Mendelian randomization results. RESULTS: Our analysis demonstrated a positive causal effect of genetically increased IIM risk on LC (odds ratio, 1.114; 95% confidence interval, 1.057-1.173; p = 5.63 × 10 -5 ), particularly on the lung squamous cell carcinoma subtype (odds ratio, 1.168, 95% confidence interval, 1.049-1.300, p = 0.00451), but not on lung adenocarcinoma or small cell lung cancer. No causal effect of LC on IIMs was identified. Sensitivity analyses indicated that horizontal pleiotropy was unlikely to influence causality, and leave-one-out analysis confirmed that the observed associations were not driven by a single-nucleotide polymorphism. CONCLUSION: Our findings offer compelling evidence of a positive causal relationship between IIMs and LC, particularly with regard to lung squamous cell carcinoma, in the European population. Conversely, there is no evidence of LC causing IIMs. We recommend that LC diagnosis consider the specific characteristics of IIMs.

Epidemiology and management of oral cavity squamous cell carcinoma in Ireland.

INTRODUCTION: The epidemiology and management of oral cavity cancer have changed considerably in recent decades. This study examines epidemiological and management trends in oral cavity squamous cell carcinoma (OCSCC). METHODS: A retrospective cohort study of data from the National Cancer Registry of Ireland between 1994 and 2014. RESULTS: A total of 2725 patients were identified. The most common subsites were the tongue (34 %, n = 1025), lip (19 %, n = 575), floor of mouth (FOM) (18 %, n = 550), and retromolar trigone (RMT) (6 %, n = 189). The incidence of OCSCC remained largely unchanged (3.14 cases/100000/year) during the study period. 5-year disease-specific survival (DSS) was 58.6 % overall, varying between subsites (lip 85 %, RMT 62.9 %, tongue 54.7 %, and FOM 47.3 %). DSS improved over the study period (p = 0.03), in particular for tongue primaries (p = 0.007). Primary surgery significantly improved DSS versus radiotherapy (HR 0.28, p < 0.0001). Survival of T4 disease managed surgically was superior to that of T1 disease managed with radiotherapy. In node positive patients, chemotherapy improved overall survival (HR 0.8 p = 0.038) but not DSS (HR 0.87 p = 0.215). CONCLUSION: Primary surgery remains the standard of care in the management of OCSCC. Prognosis has improved in line with an increase in the use of primary surgery in the same time frame, though the incidence remains unchanged.

Contrasting clinical outcomes and socio-economic impact of young versus elderly-onset oral squamous cell carcinoma, a novel health economic analysis.

OBJECTIVES: The incidence of young-onset oral squamous cell carcinoma (OSCC) is growing, even among non-smokers/drinkers. The effects of adverse histopathological features on long-term oncologic outcomes between the young and old are controversial and confounded by significant heterogeneity. Few studies have evaluated the socio-economic impact of premature mortality from OSCC. Our study seeks to quantify these differences and their economic impact on society. MATERIALS AND METHODS: Four hundred and seventy-eight young (<45 years) and 1660 old patients (≥45 years) with OSCC were studied. Logistic regression determined predictors of recurrence and death. Survival analysis was calculated via the Kaplan-Meier method. A separate health economic analysis was conducted for India and Singapore. Years of Potential Productive Life Lost (YPPLL) were estimated with the Human Capital Approach, and premature mortality cost was derived using population-level data. RESULTS: Adverse histopathological features were seen more frequently in young OSCC: PNI (42.9% vs. 35%, p = 0.002), LVI (22.4% vs. 17.3%, p = 0.013) and ENE (36% vs. 24.5%, p < 0.001). Although 5-year OS/DSS were similar, the young cohort had received more intensive adjuvant therapy (CCRT 26.9% vs. 16.6%, p < 0.001). Among Singaporean males, the premature mortality cost per death was US $396,528, and per YPPLL was US $45,486. This was US $397,402 and US $38,458 for females. Among Indian males, the premature mortality cost per death was US $30,641, and per YPPLL was US $595. This was US $ 21,038 and US $305 for females. CONCLUSION: Young-onset OSCC is an aggressive disease, mitigated by the ability to receive intensive adjuvant treatment. From our loss of productivity analysis, the socio-economic costs from premature mortality are substantial. Early cancer screening and educational outreach campaigns should be tailored to this cohort. Alongside, more funding should be diverted to genetic research, developing novel biomarkers and improving the efficacy of adjuvant treatment in OSCC.

Autoimmune disease and the risk of anal cancer in the US population aged 66 years and over.

BACKGROUND: In the United States, anal squamous cell carcinoma rates have increased rapidly, particularly among women 50 or older than 66 years of age. As immunosuppression is associated with increased risk, autoimmune conditions may be associated with greater risk of anal squamous cell carcinoma. METHODS: We conducted a population-based, case-control study using Surveillance, Epidemiology, and End Results-Medicare data (2000-2017). Anal squamous cell carcinoma cases (n = 4505) were matched to 200 000 cancer-free controls. Using multivariable logistic regression, we calculated odds ratios (ORs) and 95% confidence intervals (CIs) for associations between 47 autoimmune conditions diagnosed before selection, identified using Medicare claims, and anal squamous cell carcinoma. The Bonferroni threshold was used to correct for multiple comparisons. Population attributable fractions were calculated for conditions nominally associated with anal squamous cell carcinoma. RESULTS: In total, 18% of anal squamous cell carcinoma cases and 15% of cancer-free controls had a diagnosed autoimmune condition. Any autoimmune condition was associated with an increased risk of anal squamous cell carcinoma (OR = 1.11, 95% CI = 1.02 to 1.21; population attributable fraction = 1.8%). Anal squamous cell carcinoma was associated with systemic lupus erythematosus (OR = 1.79, 95% CI = 1.32 to 2.42; population attributable fraction = 0.4%) and nominally associated (P < .05) with sarcoidosis (OR = 2.09, 95% CI = 1.30 to 3.37; population-attributable fraction = 0.2%) and psoriasis (OR = 1.28, 95% CI = 1.06 to 1.56; population attributable fraction = 0.5%). Stratified by sex, only women showed statistically significant associations for systemic lupus erythematosus (OR = 1.97, 95% CI = 1.46 to 2.68). Statistically significant interaction was observed by sex for psoriasis (men vs women: OR = 1.68 [95% CI = 1.03 to 4.28] vs OR = 1.12 [95% CI = 0.88 to 1.43]) and polymyalgia rheumatica (OR = 0.33 [95% CI = 0.12 to 0.89] vs OR = 0.99 [95% CI = 0.75 to 1.30]). CONCLUSION: Systemic lupus erythematosus, sarcoidosis, and psoriasis were associated with a moderately increased risk of anal squamous cell carcinoma. Given these conditions' rarity and moderate associations with anal squamous cell carcinoma, autoimmune diseases cannot explain the rising trend in this disease.

Skin Cancers in Medicare Beneficiaries With Actinic Keratoses.

Importance: Actinic keratoses (AK) are common premalignant skin lesions with a small risk of progressing to cutaneous squamous cell carcinoma (SCC). There is some evidence that patients with AKs also have increased risks of other skin cancers beyond SCC. However, the absolute risks of skin cancer in patients with AKs are unknown. Objective: To calculate the absolute and relative risks of future skin cancer in Medicare beneficiaries with AKs. Design, Setting, and Participants: This retrospective cohort study was performed using a deidentified, random sample of 4 999 999 fee-for-service Medicare beneficiaries from 2009 through 2018. Patients with treated AKs were included, and patients with seborrheic keratoses (SKs) were included as a comparator group. All patients were required to have at least 1 year between data set entry and first AK or SK. Patients with a history of skin cancer were excluded. Data were analyzed from September 2022 to March 2023. Main Outcomes and Measures: Outcomes were first surgically treated skin cancer, including keratinocyte carcinoma (including SCC and basal cell carcinoma [BCC]) and melanoma. The absolute risks of skin cancer in patients with AKs were evaluated. Skin cancer risks in patients with AKs were compared with patients with SKs using adjusted competing risks regression. Results: A total of 555 945 patients with AKs (mean [SD] age, 74.0 [7.4] years; 55.4% female) and 481 024 patients with SKs (mean [SD] age, 73.3 [7.3] years; 72.4% female) were included. The absolute risk of skin cancer after a first AK was 6.3% (95% CI, 6.3%-6.4%) at 1 year, 18.4% (95% CI, 18.3%-18.5%) at 3 years, and 28.5% (95% CI, 28.4%-28.7%) at 5 years. Patients with AKs had increased risk of skin cancer compared with patients with SKs (any skin cancer: adjusted hazard ratio [aHR], 2.17; 95% CI, 2.15-2.19; keratinocyte carcinoma: aHR, 2.20; 95% CI, 2.18-2.22; SCC: aHR, 2.63; 95% CI, 2.59-2.66; BCC: aHR, 1.85; 95% CI, 1.82-1.87; and melanoma: aHR, 1.67; 95% CI, 1.60-1.73). Conclusions and Relevance: In this cohort study, older patients with AKs had substantial absolute risks, as well as elevated relative risks, of skin cancer. AKs may be clinical markers of UV exposure and increased skin cancer risk, including SCC, BCC, and melanoma. However, guidelines are lacking for follow-up skin cancer surveillance in patients with AKs. Efforts to develop evidence-based recommendations for skin cancer surveillance in patients with AKs are paramount.

Anatomic Locations of Procedurally Treated Keratinocyte Carcinomas in the US Medicare Population.

Importance: Keratinocyte carcinomas are the most common cancers in the US. However, keratinocyte carcinomas are not included in US national cancer registries, and information on the anatomic locations of keratinocyte carcinomas is lacking. Objective: To investigate the anatomic location of keratinocyte carcinomas in the US using a large claims data set. Design, Setting, and Participants: We performed a cohort study using a deidentified, random sample of 4 999 999 fee-for-service Medicare beneficiaries aged 65 years or older (2009-2018). Main Outcomes and Measures: Proportion of procedurally treated keratinocyte carcinomas at each anatomic location, identified by linking diagnosis and treatment codes. Results: A total of 2 415 514 keratinocyte carcinomas were identified in 792 393 beneficiaries. The mean (SD) age was 76.6 (8.1) years, 410 364 (51.8%) were women, and 96.7% were White. Of the 2 415 514 keratinocyte carcinomas, 796 542 could be subtyped into basal cell carcinoma (33.0%), 927 984 into squamous cell carcinoma (38.4%), and 690 988 (28.6%) could not be subtyped. The most common location of squamous cell carcinomas was the head and/or neck (44.3%) followed by upper limbs (26.7%). The most common location of basal cell carcinomas was head and/or neck (63.8%), followed by trunk (14.9%). In women, keratinocyte carcinomas were most common on the head and/or neck (47.3%) followed by upper and lower limb (18.5% and 16.6%, respectively). In men, keratinocyte carcinomas were most common on the head and/or neck (58.7%) followed by upper limb and trunk (17.3% and 11.4%, respectively). Conclusions and Relevance: The results of this large Medicare cohort study highlight the anatomic locations of keratinocyte carcinomas over recent years and show the predominance of lesions occurring at head and/or neck anatomic location. This foundational information on keratinocyte carcinoma anatomic locations in the US is valuable for improved keratinocyte risk factor differentiation and skin cancer surveillance.

Trends in keratinocyte skin cancer incidence, mortality and burden of disease in 33 countries between 1990 and 2017.

BACKGROUND: Keratinocyte cancers (KCs) are the most common type of cancer in the White population worldwide, with associated high healthcare costs. Understanding the epidemiological trends for KCs, namely basal cell carcinomas (BCCs) and cutaneous squamous cell carcinomas (SCCs), is required to assess burden of disease, project future trends and identify strategies for addressing this pressing global health issue. OBJECTIVES: To report trends in BCC and SCC incidence, and SCC mortality and disability-adjusted life-years (DALYs). METHODS: An observational study of the Global Burden of Disease (GBD) database between 1990 and 2017 was performed. European Union countries and other selected high-income countries, including the UK and the USA, classified as having high-quality mortality data, were included. Annual age-standardized incidence rates (ASIRs), age-standardized death rates (ASDRs) and DALYs for each country were obtained from the GBD database. Trends were described using joinpoint regression analysis. RESULTS: Overall, 33 countries were included. For both BCC and SCC in 2015-2017, the highest ASIRs were observed in the USA and Australia. Males had higher ASIRs than females at the end of the observation period in all countries for SCC, and in all countries but two for BCC. In contrast, the highest ASDRs for SCC were observed in Australia and Latvia for males, and in Romania and Croatia for females. The highest DALYs for SCC for both sexes were seen in Australia and Romania. Over the observation period, there were more countries demonstrating decreasing trends in mortality than in incidence, and disparities were observed between which countries had comparatively high mortality rates and which had high incidence rates. Overall reductions in SCC DALYs were observed in 24 of 33 countries for males, and 25 countries for females. CONCLUSIONS: Over the past 27 years, although trends in SCC incidence have risen in most countries, there is evidence that mortality rates have been decreasing. Burden of disease as assessed using DALYs has decreased in the majority of countries. Future work will explore potential explanatory factors for the observed disparity in trends in SCC incidence and mortality.

Clinical and economic burden of benign and malignant skin lesions in renal transplant recipients.

BACKGROUND: Studies evaluating the economic burden of dermatological care in the transplant setting are currently not available in Australia. AIMS: To evaluate the clinical and economic burden of benign and malignant skin lesions in renal transplant recipients in Central Queensland. METHODS: A bottom-up approach was used to determine the clinical burden and direct costs from patient-level Medicare data obtained from Service Australia for skin lesions. RESULTS: Seventy-six percent of the renal transplant population in Central Queensland participated in this study. The median age was 57.0 years (standard deviation ± 13.6) and the majority (61.8%) of participants were men. The mean duration after transplant surgery was 99.9 months (interquartile range, 73.2-126.6 months). During a 2-year follow-up, 22 (40%) patients were diagnosed with benign skin lesions, 21 (38%) with nonmelanoma skin carcinoma (NMSC) and one (2%) with melanoma. There was a total of 231 visits to clinicians for diagnostic and therapeutic skin procedures and the direct costs to Medicare was $48 806 Australian Dollars (AUD) or $30 427 US Dollars (USD). Approximately 86% of the total direct costs was spent for nonNMSC and mean direct costs for NMSC was $763 AUD (or $476 USD). CONCLUSION: This Medicare data-based study provides further insight into the burgeoning clinical and economic burden of the care for benign and malignant skin lesions in the renal transplantation setting in Australia.

Prevalence of HPV genotypes and assessment of their clinical relevance in laryngeal squamous cell carcinoma in a northeastern state of Brazil-a retrospective study.

Background: A high prevalence and incidence of head and neck tumors make Brazil the country with the third-highest number of cases of these malignant neoplasms. The main risk factors are smoking and alcohol consumption; however, cases related to the human papillomavirus (HPV) have tripled in number, demonstrating a changing disease profile. Studies have reported the prevalence of HPV in laryngeal squamous cell carcinoma (LSCC) to vary between 8% and 83%. The role of HPV as an important causative factor in LSCC remains unclear. Methods: This retrospective study included 82 patients with LSCC diagnosed between 2014 and 2019 at two oncology hospitals in São Luís, Brazil. Sociodemographic and clinical data, and the histopathologic characteristics of the tumors, were collected directly from medical records. Genetic material was extracted from paraffin-embedded samples using nested polymerase chain reaction (PCR) and automated sequencing for HPV detection and genotyping. The results by social and clinicopathologic variables were then compared using the chi-squared test and multivariate analysis. Results: Sociodemographic analysesdemonstrated that most patients were men (87.8%), brown-skinned (75.6%), and resident in the state capital (53.7%). They generally had a poor education status (53.7%), having only an elementary school education (completed/incomplete), and 51.2% were self-employed in occupations such as farming or fishing. Smoking and alcohol consumption habits were observed in approximately half the patients. With respect to clinical characteristics, 39% of patients exhibited T1/T2 staging, 51.2% had no distant metastasis, and 30.5% had lymph node invasion. HPV DNA was detected in half the samples (50%), with the high oncogenic type 16 being the most prevalent. There was no significant relationship observed between the economic, educational, occupational with the HPV LSCC in the presented data, although multivariate analysis demonstrated that HPV DNA was more likely to be present in T3-T4 tumors (p = 0.002).

HPV-associated oropharyngeal cancer: epidemiology, molecular biology and clinical management.

Human papillomavirus (HPV)-positive (HPV+) oropharyngeal squamous cell carcinoma (OPSCC) has one of the most rapidly increasing incidences of any cancer in high-income countries. The most recent (8th) edition of the UICC/AJCC staging system separates HPV+ OPSCC from its HPV-negative (HPV-) counterpart to account for the improved prognosis seen in the former. Indeed, owing to its improved prognosis and greater prevalence in younger individuals, numerous ongoing trials are examining the potential for treatment de-intensification as a means to improve quality of life while maintaining acceptable survival outcomes. In addition, owing to the distinct biology of HPV+ OPSCCs, targeted therapies and immunotherapies have become an area of particular interest. Importantly, OPSCC is often detected at an advanced stage owing to a lack of symptoms in the early stages; therefore, a need exists to identify and validate possible diagnostic biomarkers to aid in earlier detection. In this Review, we provide a summary of the epidemiology, molecular biology and clinical management of HPV+ OPSCC in an effort to highlight important advances in the field. Ultimately, a need exists for improved understanding of the molecular basis and clinical course of this disease to guide efforts towards early detection and precision care, and to improve patient outcomes.

Characteristics of patients diagnosed with cervical cancer in Brazil: preliminary results of the prospective cohort EVITA study (EVA001/LACOG 0215).

OBJECTIVES: Cervical cancer is the fourth most common cancer in women worldwide. Epidemiological and quality of life (QoL) data in patients with cervical cancer from low- and middle-income countries are scarce. We aimed to describe sociodemographic and clinicopathological characteristics and quality of life of patients with cervical cancer at diagnosis in Brazil. METHODS: EVITA is a prospective cohort study of newly diagnosed patients with cervical cancer from May 2016 to December 2017, stages I-IVB, from 16 Brazilian sites representing the five Brazilian regions. At baseline, medical evaluation was performed and European Organization for Research and Treatment of Cancer (EORTC) QLQ-CX24/C30 questionnaires were administered. RESULTS: A total of 631 patients were included. Mean±SD age was 49.3±13.9 years; skin color was non-white in 65.3%, and 68.0% had ≤8 years of formal education. In total, 85.1% of patients had a Pap smear. The main reasons reported by patients for not having a Pap smear were: lack of interest (46.9%), shame or embarrassment (19.7%), lack of knowledge (19.7%), and difficulty with access (9.1%). Most patients were diagnosed with locally advanced or metastatic disease (FIGO clinical stage II-IV in 81.8%- stage II in 35.2%, stage III in 36.1%, and stage IV in 10.5%). Patients with clinical stage III-IV had worse physical functioning and role functioning. CONCLUSIONS: Cervical cancer in Brazil is usually diagnosed at an advanced stage. Most patients have low formal education and are unemployed. Lack of interest was identified as a main reason for not having a screening test, and limited access was reported as a reason by <10% of the patients. Awareness campaigns must be a governmental priority, specially focused on the needy population, along with wide access to treatment.

Global, regional and national incidence, mortality and disability-adjusted life-years of skin cancers and trend analysis from 1990 to 2019: An analysis of the Global Burden of Disease Study 2019.

BACKGROUND: Information about global and local epidemiology and trends of skin cancers is limited, which increases the difficulty of cutaneous cancer control. METHODS: To estimate the global spatial patterns and temporal trends of skin cancer burden. Based on the GBD 2019, we collected and analyzed numbers and age-standardized rates (ASR) of skin cancer incidence, disability-adjusted life years (DALYs) and mortality (ASIR, ASDR, and ASMR) in 204 countries from 1990 through 2019 were estimated by age, sex, subtype (malignant skin melanoma [MSM], squamous-cell carcinoma [SCC], and basal-cell carcinoma [BCC]), Socio-demographic Index (SDI), region, and country. Temporal trends in ASR were also analyzed using estimated annual percentage change. RESULTS: Globally, in 2019, there were 4.0 million BCC, 2.4 million SCC, and 0.3 million MSM. There were approximately 62.8 thousand deaths and 1.7 million DALYs due to MSM, and 56.1 thousand deaths and 1.2 million DALYs were attributed to SCC, respectively. The men had higher ASR of skin cancer burden than women. The age-specific rates of global skin cancer burden were higher in the older adults, increasing trends observed from 55 years old. Geographically, the numbers and ASR of skin cancers varied greatly across countries, with the largest burden of ASIR in high SDI regions. However, an unexpected increase was observed in some regions from 1990 to 2019, such as East Asia, and Sub-Saharan Africa. Although there was a slight decrease of the ASMR and ASDR, the global ASIR of MSM dramatically increased, 1990-2019. Also, there was a remarkable increase in ASR of BCC and SCC burden. CONCLUSIONS: Skin cancer remains a major global public health threat. Reducing morbidity and mortality strategies such as primary and secondary prevention should be reconsidered, especially in the most prevalent and unexpected increased regions, especially for those areas with the greatest proportions of their population over age 55.

United States burden of melanoma and non-melanoma skin cancer from 1990 to 2019.

BACKGROUND: Skin cancer is the most common cancer worldwide. OBJECTIVE: To evaluate the burden of skin cancer in the US from 1990 to 2019. METHODS: Age-standardized incidence, prevalence, disability-adjusted life years (DALY), and mortality rates from skin cancer in the US were evaluated from the Global Burden of Disease 2019. RESULTS: Incidence, prevalence, DALY, and mortality rates for melanoma per 100,000 persons in 2019 were 17.0, 138, 64.8, and 2.2, respectively; for squamous cell carcinoma, rates were 262, 314, 26.6, and 0.8, respectively; and for basal cell carcinoma, rates were 525, 51.2, 0.2, and zero, respectively. Incidence and prevalence rates of melanoma and non-melanoma skin cancer (NMSC) have increased since 1990, while mortality rates have remained fairly stable. Males have had higher incidence, prevalence, DALY, and mortality rates from melanoma and NMSC every year since 1990. Incidence and prevalence of melanoma was relatively higher in the northern half of the US than in the southern half. LIMITATIONS: Global Burden of Disease is derived from estimation and mathematical modeling. CONCLUSIONS: Health care professionals can utilize differences and trends noted in this study to guide allocation of resources to reduce incidence and morbidity from skin cancer.

A Non-Surgical and Cost-Effective Treatment Approach Employing Topical Imiquimod, 5-Fluorouracil, and Tretinoin for Primary Non-Melanoma Skin Cancers.

BACKGROUND: Minimally invasive alternative approaches to treat non-melanoma skin cancers remain limited and unproven. OBJECTIVE: We aim to assess the efficacy of varying combinations of anti-tumor agents—imiquimod 5% cream, 5-fluorouracil 2% solution, and tretinoin 0.1% cream—with brief cryotherapy in treating non-melanoma skin cancers. METHODS: This retrospective study included 690 cases of non-melanoma skin cancers in 480 patients who received a diagnosis of a basal cell carcinoma or squamous cell carcinoma during a ten-year period. During treatment period, patients applied 30 applications of one of three combinations (imiquimod/tretinoin, 5-fluorouracil/tretinoin, or imiquimod/5-fluorouracil/tretinoin) and had cryotherapy every 2 weeks. Each patient had a clinical examination at least three years post-treatment or documented treatment failure. Clearance was defined by a lack of persistence or recurrence for 3 years following the completion of treatment. The likelihood of lesion clearance was evaluated using multivariable logistic regression analysis. RESULTS: A total of 186 cases (97; basal cell carcinoma and 89; squamous cell carcinoma) in 133 patients [37% women and 63% men; median (interquartile range) age, 77 (69, 83) years] met the inclusion criteria. Multivariable logistic regression analysis adjusting for clinical and lesion variables demonstrated that, relative to the imiquimod/5-fluorouracil/tretinoin treatment approach, imiquimod/ tretinoin (odds ratio, 0.05; 95% confidence interval, 0.00-0.99) and 5-fluorouracil/tretinoin (0.02; 0.00–0.45) were associated with lower likelihoods of lesion clearance. Likewise, morpheaform basal cell carcinoma had a lower probability of clearance (0.05; 0.00–0.72). CONCLUSIONS: The combination of imiquimod/5-fluorouracil/tretinoin with cryotherapy had high clearance rates and was the most effective treatment regimen. J Drugs Dermatol. 2021;20(3):260-267. doi:10.36849/JDD.5427.

Socioeconomic status and skin cancer incidence: a population-based, cohort study in the province of Ferrara, northern Italy.

To assess the impact of socioeconomic status (SES) on the occurrence of skin cancer in the population living in the province of Ferrara, Italy, a retrospective cohort of patients with squamous cell carcinoma (SCC), basal cell carcinoma (BCC) or malignant melanoma (MM), provided by the local cancer registry, was investigated. The SES was expressed through an ecological-based deprivation index. During the 8-year study period (2006-2013, total person-years 2 859 137), 6051 carcinomas (1535 SCCs, 4365 BCCs) and 459 MMs were diagnosed. Both crude and standardized (on the European population) rates and the standardized incidence ratio showed a direct correlation between BCC and SES. Multivariate analysis confirmed these results for BCC and also for MM, while it showed an excess of SCC incidence in the lowest SES subgroup. This study shows, for the first time, to our knowledge, opposite effects of SES on SCC and BCC occurrence. A role of environmental factors conditioned by SES may be hypothesized.

Advanced keratinocyte skin cancer is a tumor with considerable disease burden and aggressiveness.

In a 2013 study published in this Journal, Dacosta Byfield et al. used MediCare data to extract reliable estimations of the incidence (I = 6.16) and prevalence (P = 10.31) rates of advanced keratinocyte skin cancer (aKSC) per 100,000 US population. These data unmask a considerable disease burden of aKSC (tumor stages ≥ 3) compared to the corresponding projected SEER predictions in 2019 of all invasive cases (tumor stages ≥ 1). According to its incidence, aKSC ranks 19th out of 29 major SEER registered neoplasms and has an average disease duration of 1.67 years, which is the second shortest disease duration next only to pancreatic carcinoma. Furthermore, in support of the high disease aggressiveness of aKSC and using a calibration approach, we calculated a mortality estimate of 4.64 per 100,000 and a 5-year survival rate of 21.8% for this tumor, which corresponds to positions of 13th and 5th out of 29 cancers among the SEER tracked malignancies, respectively. Taken together, these data indicate a considerable disease burden and biologic aggressiveness of aKSC.