BACKGROUND: A subset of patients affected by cutaneous squamous cell carcinoma (cSCC) can exhibit locally invasive or metastatic tumors. Different staging classification systems are currently in use for cSCC. However, precise patient risk stratification has yet to be reached in clinical practice. The study aims to identify specific histological and molecular parameters characterizing metastatic cSCC.
METHODS: Patients affected by metastatic and non-metastatic cSCC (controls) were included in the present study and matched for clinical and histological characteristics. Skin samples from primary tumors were revised for several histological parameters and also underwent gene expression profiling with a commercially available panel testing 770 different genes.
RESULTS: In total, 48 subjects were enrolled in the study (24 cases, 24 controls); 67 genes were found to be differentially expressed between metastatic and non-metastatic cSCC. Most such genes were involved in immune regulation, skin integrity, angiogenesis, cell migration and proliferation.
CONCLUSIONS: The combination of histological and molecular profiles of cSCCs allows the identification of features specific to metastatic cSCC, with potential implications for more precise patient risk stratification.

The incidences of anogenital HPV-related cancers in women are on the rise; this is especially true for anal cancer. Medical societies are now beginning to recommend anal cancer screening in certain high-risk populations, including high-risk women with a history of genital dysplasia. The aim of this study is to investigate national anogenital HPV cancer trends as well as the role of demographics, deprivation, and ethnicity on anogenital cancer incidence in England, in an attempt to better understand this cohort of women which is increasingly affected by anogenital HPV-related disease. Demographic data from the Clinical Outcomes and Services Dataset (COSD) were extracted for all patients diagnosed with anal, cervical, vulval and vaginal cancer in England between 2014 and 2020. Outcomes included age, ethnicity, deprivation status and staging. An age over 55 years, non-white ethnicity and high deprivation are significant risk factors for late cancer staging, as per logistic regression. In 2019, the incidences of anal and vulval cancer in white women aged 55-74 years surpassed that of cervical cancer. More needs to be done to educate women on HPV-related disease and their lifetime risk of these conditions.

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BACKGROUND: CELF2 belongs to the CELF RNA-binding protein family and exhibits antitumor activity in various tumor models. Analysis of the pan-cancer TCGA database reveals that CELF2 expression strongly correlates with favorable prognosis among cancer patients. The function of CELF2 in nonmelanoma skin cancer has not been studied.
METHODS: We used shRNA-mediated knockdown (KD) of CELF2 expression in human squamous cell carcinoma (SCC) cells to investigate how CELF2 impacted SCC cell proliferation, survival, and xenograft tumor growth. We determined CELF2 expression in human SCC tissues and adjacent normal skin using immunofluorescence staining. Additionally, we investigated the changes in CELF2 and its target gene expression during UV-induced and chemical-induced skin tumorigenesis by western blotting.
RESULTS: CELF2 KD significantly increased SCC cell proliferation, colony growth, and SCC xenograft tumor growth in immunodeficient mice. CELF2 KD in SCC cells led to activation of KRT80 and GDF15, which can potentially promote cell proliferation and tumor growth. While control SCC cells were sensitive to anticancer drugs such as doxorubicin, SCC cells with CELF2 KD became resistant to drug-induced tumor growth retardation. Finally, we found CELF2 expression diminished during both UV- and chemical-induced skin tumorigenesis in mice, consistent with reduced CELF2 expression in human SCC tumors compared to adjacent normal skin.
CONCLUSIONS: This study shows for the first time that CELF2 loss occurs during skin tumorigenesis and increases drug resistance in SCC cells, highlighting the possibility of targeting CELF2-regulated pathways in skin cancer prevention and therapies.

UNASSIGNED: Penile squamous cell carcinoma (SCC) is an extremely rare malignancy. It is usually caused by chronic human papillomavirus (HPV) 16 and HPV 18 infections. This study was conducted to investigate the immunohistochemical overexpression of p16, a surrogate marker for HPV, and to evaluate its usefulness as a potential diagnostic biomarker.
UNASSIGNED: In this cross-sectional prospective and retrospective cohort study, 56 penile squamous cell carcinoma (SCC) specimens and five penile premalignant specimens were evaluated in Kasturba Medical College, Mangalore, India, from January 2013- December 2018 in terms of clinical and histopathological features. Immunohistochemical expression for p16 in cases and controls was evaluated. Statistical comparison of p16 expression among clinical features, histological subtype, grade, and stages of tumor were done.
UNASSIGNED: Analysis of the pattern of p16 staining showed diffuse and strong nuclear and cytoplasmic expression in 32.8% of the cases. There was a highly significant association (P<0.001) of pattern of p16 expression among the HPV and non-HPV subtypes of penile carcinoma. p16 expression was not significantly associated with other prognostic parameters like site of the lesion, lymphovascular invasion, perineural invasion, histologic grade, and pathologic stage.
UNASSIGNED: Expression of p16 would be a useful tool in differentiation between the HPV-associated and non-HPV-associated subtypes of penile SCC that may be helpful in prediction of aggressiveness and invasive potential of the respective histologic subtypes.

Stress corrosion cracking (SCC) under harsh environmental conditions still poses a significant challenge, despite extensive research efforts. The intricate interplay among mechanical, chemical, and electrochemical factors hinders the accurate prognosis of material degradation and remaining service life. Furthermore, the demand for real-time monitoring and early detection of SCC defects adds further complexity to the prognostication process. Therefore, there is an urgent need for comprehensive review papers that consolidate current knowledge and advancements in prognosis methods. Such reviews would facilitate a better understanding and resolution of the challenges associated with SCC under harsh environmental conditions. This work aims to provide a comprehensive overview of various prognosis methods utilized for the assessment and prediction of SCC in such environments. The paper will delve into the following sections: exacerbating harsh environmental conditions, non-destructive testing (NDT) techniques, electrochemical techniques, numerical modeling, and machine learning. This review is inclined to serve as a valuable resource for researchers and practitioners working in the field, facilitating the development of effective strategies to mitigate SCC and ensure the integrity and reliability of materials operating in challenging environments. Despite considerable research, stress corrosion cracking in harsh environments remains a critical issue, complicated by the interplay of mechanical, chemical, and electrochemical factors. This review aims to consolidate current prognosis methods, including non-destructive testing, electrochemical techniques, numerical modeling, and machine learning. Key findings indicate that while traditional methods offer limited reliability, emerging computational approaches show promise for real-time, accurate predictions. The paper also briefly discusses notable SCC failure cases to underscore the urgency for improved prognosis techniques. This work aspires to fill knowledge gaps and serve as a resource for developing effective SCC mitigation strategies, thereby ensuring material integrity in challenging operational conditions.

Cancer-associated fibroblasts (CAFs) interact reciprocally with tumor cells through various signaling pathways in many cancer types including cutaneous squamous cell carcinoma (cSCC). Among normal fibroblast (NF) subtypes, papillary fibroblasts (PFs) and reticular fibroblasts (RFs) respond distinctly to tumor cell signaling, eventuating the differentiation of RFs, rather than PFs, into CAFs. The regulation of subtype differentiation in fibroblasts remains poorly explored. In this study, we assessed the differences between PFs, RFs, and CAFs, and examined the effects of small-molecule inhibitors targeting the TGFβ, PI3K/AKT/mTOR, and NOTCH pathways on the tumor-promoting property of CAFs and CAF reprogramming in 2D and 3D cultures. Blocking TGFβ and PI3K strongly deactivated and concurrently induced a PF phenotype in RFs and CAFs. 3D co-culturing a cSCC cell line MET2 with RFs or CAFs led to enhanced tumor invasion, \"RF-CAF\" transition and cytokine production, which were further repressed by blocking TGFβ and PI3K/mTOR pathways, but not NOTCH pathway. In conclusion, the study identified biomarkers for PFs, RFs and CAFs, and displayed different effects of blocking key signaling pathways in CAFs and tumor cell-CAF interplay. These findings prompted a \"CAF to PF\" therapeutic strategy, and provided perspectives of using included inhibitors in CAF-based cancer therapy.

BACKGROUND: Vulval cancer is a rare gynaecological malignancy. In this study, we present a tertiary centre case analysis to examine the recurrence patterns and survival outcomes of vulval squamous cell carcinoma (SCC).
METHODS: This is a retrospective cohort study of women who received treatment at Oxford University Hospitals between February 2010 and July 2022 for primary vulval SCC.
RESULTS: We included 98 cases. The median age at diagnosis was 68 years. Human Papillomavirus (HPV) infection and lichen sclerosis were observed in 21 and 50 cases, respectively. Surgical excision was the primary treatment. Recurrence within 2 years was more common with advanced stage (p = 0.047, RR = 2.26) and extracapsular lymph node spread (p = 0.013, RR = 2.88). Local recurrence was not associated with a specific cut-off value for tumour-free margin. Poor survival outcomes were observed with higher grade (p = 0.01), advanced FIGO stage (p < 0.001), HPV-independent cancer (p = 0.048), lymph node involvement (p < 0.001, HR = 7.14), extracapsular spread (p < 0.001, HR = 7.93), lymphovascular space invasion (p = 0.002, HR = 3.17), tumour diameter wider than 23 mm (p = 0.029, HR = 2.53) and depth of invasion more than 6 mm (p = 0.006, HR = 3.62). Perineural invasion is associated with shorter disease-free survival. Five-year cancer-specific survival rates for stages I, III, and IV were 90.2%, 40.8%, and 14.3%, respectively.
CONCLUSIONS:

UNASSIGNED: Actinic Keratoses (AK) are precancerous lesions that can lead to Squamous Cell Carcinoma. International differences in the utilization of topical medications to treat AK are not well described.
UNASSIGNED: To describe international differences in topical AK medication utilization, including associations of countries\' economic status with AK medication utilization.
UNASSIGNED: We used IQVIA MIDAS pharmaceutical sales data for 65 countries (42 high-income, 24 middle-income) from April 2011 to December 2021. We calculated each country\'s quarterly utilization of medications in grams per 1000 population. We used univariable linear regression to assess the association between country economic status and AK medication utilization.
UNASSIGNED: High-income countries used 15.37 more grams per 1000 population of 5-fluorouracil (95% CI: 9.68, 21.05), 4.64 more grams per 1000 population of imiquimod (95% CI: 3.45, 5.83), and 0.32 more grams per 1000 population of ingenol mebutate (95% CI: 0.05, 0.60).
UNASSIGNED: Missing medication utilization data for some countries.
UNASSIGNED: High-income countries use more topical AK therapies than middle-income countries.

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