ABSTRACT
Oral squamous cell carcinoma (OSCC) is a serious public health problem in various Asian countries, including Sri Lanka, and a combination of cultural practices, lifestyle factors, and genetic predispositions influences the incidence of these cancers. The examination of the connection between exposure to heavy metals and the probability of developing oral potentially malignant disorders (OPMD) and OSCC has been limited in its scope, and the overall consequences of such exposure remain largely unknown. This study aims to clarify the link between serum levels of heavy metals and the risk of OSCC and OPMD. The concentrations of seven heavy metals-namely, arsenic (As), cadmium (Cd), chromium (Cr), cobalt (Co), copper (Cu), lead (Pb), and zinc (Zn)-were analyzed in serum samples from 60 cases and 15 controls in the Sri Lankan cohort. The Inductively Coupled Plasma-Optical Emission Spectrometry (ICP-OES) was used for the analysis. Subsequently, the data underwent statistical evaluation via the Kruskal-Wallis H test, using the Statistical Package for Social Sciences (SPSS) version 28 software, with a confidence interval set at 95%. A p-value less than 0.05 was considered statistically significant. The cohort consisted of 48 men and 27 women, with 15 patients each diagnosed with OSCC, OSF, OLK, and OLP, and 15 healthy controls. The study used the Kruskal-Wallis Test to compare metal concentrations across groups, finding significant differences for all metals except As and Pb. Significant associations were observed between age, past medical history, drug history, gender, smoking, alcohol consumption, and betel chewing. The Spearman Correlation test showed significant correlations between the concentrations of Cr, Co, Cu, As, and Zn and the presence of cancer/precancer conditions. The study's findings suggest that heavy metal contamination may be linked to the development of OSCC and precancerous conditions. When comparing OSCC and OPMD cases with controls, the serum concentrations of As and Pb did not differ significantly. However, Cd, Cr, Co, Cu, and Zn exhibited significantly higher concentrations among cases compared to controls (p < 0.05). This study observed significant variations in the levels of these five heavy metals among cancerous (OSCC), premalignant (OPMD), and healthy tissues, suggesting a potential role in the progression of malignancies. These findings underscore the importance of environmental pollution in this specific context.
Subject(s)
Carcinoma, Squamous Cell , Metals, Heavy , Mouth Neoplasms , Humans , Male , Female , Metals, Heavy/blood , Metals, Heavy/adverse effects , Mouth Neoplasms/blood , Mouth Neoplasms/etiology , Mouth Neoplasms/epidemiology , Mouth Neoplasms/chemically induced , Middle Aged , Carcinoma, Squamous Cell/blood , Carcinoma, Squamous Cell/chemically induced , Carcinoma, Squamous Cell/epidemiology , Carcinoma, Squamous Cell/etiology , Adult , Sri Lanka/epidemiology , Aged , Case-Control Studies , Risk Factors , Squamous Cell Carcinoma of Head and Neck/blood , Squamous Cell Carcinoma of Head and Neck/chemically induced , Squamous Cell Carcinoma of Head and Neck/epidemiology , Arsenic/blood , Arsenic/adverse effectsABSTRACT
PURPOSE: A MASCC/ISOO Clinical Practice Statement (CPS) is aimed at generating a concise tool for clinicians that concentrates practical information needed for the management of oral complications of cancer patients. This CPS is focused on the risk of secondary oral cancer following hematopoietic cell transplantation (HCT). METHODS: This CPS was developed based on critical evaluation of the literature followed by a structured discussion of a group of leading experts, members of the Oral Care Study Group of MASCC/ISOO. The information is presented in the form of succinct bullets to generate a short manual about the best standard of care. RESULTS: Studies described a 7-16-fold higher risk of secondary oral cancer (mainly squamous cell carcinoma) in allogeneic HCT (alloHCT) recipients, particularly in those who developed chronic graft versus host disease (cGVHD). Risk increases over time and is influenced by several risk factors. In autologous HCT, oral cancer risk seemed only slightly elevated. CONCLUSION: Clinicians should be aware of the higher oral cancer risk in alloHCT survivors, and emphasize the importance of lifelong oral cancer surveillance (at least every 6-12 months) and avoiding cancer promoting lifestyle factors in an empathic way, particularly of those with (a history of) cGVHD. Post-HCT for Fanconi anemia or dyskeratosis congenita, education and rigorous follow-up is even more crucial. In case of suspected oral lesions in the presence of oral mucosal cGVHD, a GVHD intervention may facilitate diagnosis. Suspected lesions should be biopsied. More research is needed on the role of HPV in oral cancer post-HCT.
Subject(s)
Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Mouth Neoplasms , Humans , Hematopoietic Stem Cell Transplantation/adverse effects , Hematopoietic Stem Cell Transplantation/methods , Mouth Neoplasms/etiology , Graft vs Host Disease/etiology , Risk Factors , Carcinoma, Squamous Cell/etiology , Neoplasms, Second Primary/etiologyABSTRACT
BACKGROUND: Oral cavity squamous cell carcinomas (OCSCCs) are relatively common in multiple non-human primate species but are poorly documented in Goeldi's monkeys. METHODS: Four Goeldi's monkeys with OCSCC, from three zoological collections, underwent necropsy with cytology, histopathology, immunohistochemistry, and pan-herpesvirus PCR analysis. RESULTS: All animals were euthanised and exhibited poor-to-emaciated body condition. Three OCSCCs arose from the maxillary oral mucosa and a single OCSCC was primarily mandibular, with bone invasion evident in three cases. Histologically, one OCSCC in situ was diagnosed, whilst the rest were typically invasive OCSCCs. Neoplastic cells were immunopositive for pancytokeratin and E-cadherin. All examined cases were negative for regional lymph node (RLN) and/or distant metastases, cyclooxygenase-2 (COX-2) immunoexpression, and panherpesvirus PCR expression. CONCLUSIONS: OCSCCs in Goeldi's monkeys may be deeply invasive, but not readily metastatic. No herpesvirus-association or COX-2 expression was evident; the latter suggesting that NSAIDs are unlikely to be a viable chemotherapeutic treatment.
Subject(s)
Animals, Zoo , Carcinoma, Squamous Cell , Monkey Diseases , Mouth Neoplasms , Animals , Carcinoma, Squamous Cell/veterinary , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/etiology , Carcinoma, Squamous Cell/virology , Mouth Neoplasms/veterinary , Mouth Neoplasms/pathology , Mouth Neoplasms/etiology , Monkey Diseases/pathology , Monkey Diseases/virology , Male , FemaleABSTRACT
Oral squamous cell carcinoma (OSCC) is the most common malignant tumor of the head and neck with an extremely poor five-year survival rate of approximately 50 to 55%, despite significant advances in diagnostic and therapeutic procedures over the past three decades [...].
Subject(s)
Carcinogenesis , Mouth Neoplasms , Humans , Mouth Neoplasms/therapy , Mouth Neoplasms/etiology , Mouth Neoplasms/pathology , Carcinogenesis/pathology , Carcinoma, Squamous Cell/therapy , Carcinoma, Squamous Cell/etiology , Carcinoma, Squamous Cell/pathologyABSTRACT
It has long been recognized that a history of skin cancer puts one at risk for additional primary skin cancers. However, more variable data exists for the risk of developing a non-cutaneous primary cancer following a diagnosis of skin cancer. The data are most variable for Basal Cell Carcinoma (BCC), the most common and least aggressive type of skin cancer. While early studies imply that BCC does not impart a larger risk of other primary non-cutaneous cancers, more recent studies with larger populations suggest otherwise. The cancers most significantly associated with BCC are lip, oropharyngeal, and salivary gland cancer. There is also burgeoning evidence to suggest a link between BCC and prostate, breast, and colorectal cancer, but more data are needed to draw a concrete conclusion. Squamous Cell Carcinoma (SCC), the second most common type of skin cancer, has a slightly more defined risk to other non-cutaneous primary malignancies. There is a notable link between SCC and non-Hodgkin's lymphoma (NHL), possibly due to immunosuppression. There is also an increased risk of other cancers derived from squamous epithelium following SCC, including oropharyngeal, lip, and salivary gland cancer. Some studies also suggest an increased risk of respiratory tract cancer following SCC, possibly due to shared risk factors. Melanoma, a more severe type of skin cancer, shows a well-defined risk of additional primary non-cutaneous malignancies. The most significant of these risks include NHL, thyroid cancer, prostate cancer, and breast cancer along with a host of other cancers. Each of these three main skin cancer types has a profile of genetic mutations that have also been linked to non-cutaneous malignancies. In this review, we discuss a selection of these genes to highlight the complex interplay between different tumorigenesis processes.
Subject(s)
Carcinoma, Basal Cell , Skin Neoplasms , Humans , Skin Neoplasms/epidemiology , Skin Neoplasms/pathology , Skin Neoplasms/etiology , Carcinoma, Basal Cell/epidemiology , Carcinoma, Basal Cell/etiology , Carcinoma, Basal Cell/pathology , Carcinoma, Squamous Cell/epidemiology , Carcinoma, Squamous Cell/etiology , Carcinoma, Squamous Cell/pathology , Melanoma/epidemiology , Melanoma/etiology , Melanoma/pathology , Risk FactorsABSTRACT
OBJECTIVE: Previous isolated reports have hypothesized that chewing coca leaves, a pre-Columbian tradition found in certain regions of South America, may be associated with the development of oral squamous cell carcinoma (OSCC). Coca chewing (CC) is a habit that shares many characteristics with the well-known practice of betel chewing observed in Asia. The aim of this study is to analyze the association between CC and OSCC among patients who attended the Señor del Milagro Hospital in Salta, Argentina. STUDY DESIGN: A case-control study was conducted from 2013 to 2018. For each case of OSCC, three healthy control patients were included. Odds ratios were calculated to compare demographics, concurrent oral conditions, and other classical risk factors for OSCC. RESULTS: A total of 62 cases and 180 controls were included, adjusted for sex and age. OSCC was significantly associated with tobacco use (27.4% vs 9.4%, P = .001), CC (62.9% vs 32.2%, P < .001), and poor oral condition (81.1% vs 67.7%, P = .02). In the multivariate analysis, smoking (OR = 2.77, 95% CI 1.23-6.25, P = .0139), CC (OR = 2.98, 95% CI 1.58-5.63, P = .0007), and poor oral condition (OR = 3.1, 95% CI 1.62-5.85, P = .0006) remained independently associated with OSCC development. CONCLUSIONS: Chewing coca leaves could be considered a risk factor for oral cancer in a subset of Argentinean patients. Further studies are necessary to validate our findings and to elucidate the underlying pathways linking this habit to oral carcinogenesis.
Subject(s)
Carcinoma, Squamous Cell , Coca , Mouth Neoplasms , Humans , Case-Control Studies , Argentina , Female , Male , Mouth Neoplasms/epidemiology , Mouth Neoplasms/etiology , Middle Aged , Risk Factors , Carcinoma, Squamous Cell/epidemiology , Carcinoma, Squamous Cell/etiology , Aged , Mastication , Adult , Plant LeavesABSTRACT
Periodontitis is linked to the onset and progression of oral squamous cell carcinoma (OSCC), an epidemiologically frequent and clinically aggressive malignancy. In this context, Fusobacterium (F.) nucleatum and Porphyromonas (P.) gingivalis, two bacteria that cause periodontitis, are found in OSCC tissues as well as in oral premalignant lesions, where they exert pro-tumorigenic activities. Since the two bacteria are present also in endodontic diseases, playing a role in their pathogenesis, here we analyze the literature searching for information on the impact that endodontic infection by P. gingivalis or F. nucleatum could have on cellular and molecular events involved in oral carcinogenesis. Results from the reviewed papers indicate that infection by P. gingivalis and/or F. nucleatum triggers the production of inflammatory cytokines and growth factors in dental pulp cells or periodontal cells, affecting the survival, proliferation, invasion, and differentiation of OSCC cells. In addition, the two bacteria and the cytokines they induce halt the differentiation and stimulate the proliferation and invasion of stem cells populating the dental pulp or the periodontium. Although most of the literature confutes the possibility that bacteria-induced endodontic inflammatory diseases could impact on oral carcinogenesis, the papers we have analyzed and discussed herein recommend further investigations on this topic.
Subject(s)
Fusobacterium Infections , Fusobacterium nucleatum , Mouth Neoplasms , Porphyromonas gingivalis , Humans , Porphyromonas gingivalis/pathogenicity , Fusobacterium nucleatum/pathogenicity , Mouth Neoplasms/microbiology , Mouth Neoplasms/pathology , Fusobacterium Infections/microbiology , Fusobacterium Infections/complications , Carcinogenesis , Bacteroidaceae Infections/microbiology , Bacteroidaceae Infections/complications , Carcinoma, Squamous Cell/microbiology , Carcinoma, Squamous Cell/etiology , Carcinoma, Squamous Cell/pathology , Periodontitis/microbiology , Animals , Cytokines/metabolismABSTRACT
Epidermolysis bullosa (EB) is an umbrella term for a group of rare inherited skin disorders characterised by mucocutaneous fragility. Patients suffer from blisters and chronic wounds that arise spontaneously or following minor mechanical trauma, often resulting in inflammation, scarring and fibrosis due to poor healing. The recessive form of dystrophic EB (RDEB) has a particularly severe phenotype and is caused by mutations in the COL7A1 gene, encoding the collagen VII protein, which is responsible for adhering the epidermis and dermis together. One of the most feared and devastating complications of RDEB is the development of an aggressive form of cutaneous squamous cell carcinoma (cSCC), which is the main cause of mortality in this patient group. However, pathological drivers behind the development and progression of RDEB-associated cSCC (RDEB-cSCC) remain somewhat of an enigma, and the evidence to date points towards a complex process. Currently, there is no cure for RDEB-cSCC, and treatments primarily focus on prevention, symptom management and support. Therefore, there is an urgent need for a comprehensive understanding of this cancer's pathogenesis, with the aim of facilitating the discovery of drug targets. This review explores the current knowledge of RDEB-cSCC, emphasising the important role of the immune system, genetics, fibrosis, and the tumour-promoting microenvironment, all ultimately intricately interconnected.
Subject(s)
Carcinoma, Squamous Cell , Collagen Type VII , Epidermolysis Bullosa Dystrophica , Skin Neoplasms , Humans , Epidermolysis Bullosa Dystrophica/genetics , Epidermolysis Bullosa Dystrophica/pathology , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/etiology , Skin Neoplasms/genetics , Skin Neoplasms/pathology , Skin Neoplasms/immunology , Collagen Type VII/genetics , Mutation , Animals , Tumor Microenvironment/genetics , Tumor Microenvironment/immunology , Fibrosis , Genes, RecessiveABSTRACT
Voriconazole exposure is associated with skin cancer, but it is unknown how the full spectrum of its metabolizer phenotypes impacts this association. We conducted a retrospective cohort study to determine how variation in metabolism of voriconazole as measured by metabolizer status of CYP2C19 is associated with the total number of skin cancers a patient develops and the rate of development of the first skin cancer after treatment. There were 1,739 organ transplant recipients with data on CYP2C19 phenotype. Of these, 134 were exposed to voriconazole. There was a significant difference in the number of skin cancers after transplant based on exposure to voriconazole, metabolizer phenotype, and the interaction of these two (p < 0.01 for all three). This increase was driven primarily by number of squamous cell carcinomas among rapid metabolizes with voriconazole exposure (p < 0.01 for both). Patients exposed to voriconazole developed skin cancers more rapidly than those without exposure (Fine-Grey hazard ratio 1.78, 95% confidence interval 1.19-2.66). This association was similarly driven by development of SCC (Fine-Grey hazard ratio 1.83, 95% confidence interval 1.14-2.94). Differences in voriconazoles metabolism are associated with an increase in the number of skin cancers developed after transplant, particularly SCC.
Subject(s)
Antifungal Agents , Carcinoma, Squamous Cell , Cytochrome P-450 CYP2C19 , Skin Neoplasms , Voriconazole , Humans , Voriconazole/adverse effects , Skin Neoplasms/epidemiology , Skin Neoplasms/etiology , Skin Neoplasms/metabolism , Retrospective Studies , Male , Female , Middle Aged , Antifungal Agents/adverse effects , Carcinoma, Squamous Cell/epidemiology , Carcinoma, Squamous Cell/metabolism , Carcinoma, Squamous Cell/etiology , Cytochrome P-450 CYP2C19/metabolism , Cytochrome P-450 CYP2C19/genetics , Aged , Organ Transplantation/adverse effects , AdultABSTRACT
Cutaneous squamous cell carcinoma (cSCC) is the second most prevalent form of skin cancer, with an escalating incidence rate and a notable potential (up to 5%) for metastasis. Ultraviolet radiation (UVA and UVB) exposure is the primary risk factor for cSCC carcinogenesis, with literature suggesting ultraviolet radiation (UVR) promotes vascular endothelial growth factor A (VEGFA) expression. This study aims to investigate UVR-induced upregulation of VEGFA and explore combination therapeutic strategies. The skin squamous cell carcinoma cell line A431 was exposed to specific durations of ultraviolet radiation. The effect of emodin on ATR/SerRS/VEGFA pathway was observed. The cell masses were also transplanted subcutaneously into mice (n = 8). ATR inhibitor combined with emodin was used to observe the growth and angiogenesis of the xenografts. The results showed that UV treatment significantly enhanced the phosphorylation of SerRS and the expression level of VEGFA in A431 cells (p < 0.05). Treatment with emodin significantly inhibited this expression (p < 0.05), and the combination of emodin and ATR inhibitor further enhanced the inhibitory effect (p < 0.05). This phenomenon was further confirmed in the xenograft model, which showed that the combination of ATR inhibitor and emodin significantly inhibited the expression of VEGFA to inhibit angiogenesis (p < 0.05), thus showing an inhibitory effect on cSCC. This study innovatively reveals the molecular mechanism of UV-induced angiogenesis in cSCC and confirms SerRS as a novel target to inhibit cSCC angiogenesis and progression in vitro and in vivo studies.
Subject(s)
Ataxia Telangiectasia Mutated Proteins , Carcinoma, Squamous Cell , Neovascularization, Pathologic , Skin Neoplasms , Ultraviolet Rays , Vascular Endothelial Growth Factor A , Animals , Vascular Endothelial Growth Factor A/metabolism , Vascular Endothelial Growth Factor A/genetics , Skin Neoplasms/pathology , Skin Neoplasms/etiology , Skin Neoplasms/metabolism , Ultraviolet Rays/adverse effects , Carcinoma, Squamous Cell/metabolism , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/etiology , Carcinoma, Squamous Cell/drug therapy , Humans , Mice , Neovascularization, Pathologic/metabolism , Cell Line, Tumor , Ataxia Telangiectasia Mutated Proteins/metabolism , Ataxia Telangiectasia Mutated Proteins/antagonists & inhibitors , Xenograft Model Antitumor Assays , Signal Transduction/drug effects , Mice, Nude , Gene Expression Regulation, Neoplastic/drug effects , Gene Expression Regulation, Neoplastic/radiation effects , Emodin/pharmacology , Cell Proliferation/drug effects , Mice, Inbred BALB C , AngiogenesisABSTRACT
Exposure to solar ultraviolet (UV) radiation and use of UV-emitting tanning devices are known risk factors for skin cancer. Few studies have explored the interaction between these risk factors, namely how the risk of skin cancer increases among those who both have been exposed to high levels of natural sunlight and regularly use tanning beds. Nurses' Health Study II followed 116,430 women, aged 25-42, from 1991 to 2011. Cumulative average UV exposure was based on participants' residences at follow-up periods. History of severe sunburn during ages 15-20 was used as a proxy for early-life sunlight exposure. Tanning bed use in early life data was collected. Participants reported melanoma, basal cell carcinoma (BCC), and squamous cell carcinoma (SCC) diagnoses. We built multivariable Cox regression models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for risk of skin cancer associated with joint effects of sunlight exposure and tanning bed use. Participants with high sunlight exposure and tanning bed use during high school/college had an increased risk of BCC (HR = 1.53, 95% CI 1.37-1.71, Pinteraction=0.01; vs. low sun exposure and no tanning bed use). Participants with a history of severe sunburns and tanning bed use during high school/college were at increased risk of BCC (HR = 1.62, 95% CI 1.47-1.79, Pinteraction=0.02; vs. no sunburns and no tanning bed use). No significant interactions were found between sunlight exposure and tanning bed use on SCC and melanoma risk. We found significant interactions between sunlight exposure and tanning bed use on the risk of BCC.
Subject(s)
Carcinoma, Basal Cell , Carcinoma, Squamous Cell , Melanoma , Skin Neoplasms , Sunbathing , Sunlight , Humans , Female , Skin Neoplasms/etiology , Skin Neoplasms/epidemiology , Carcinoma, Basal Cell/epidemiology , Carcinoma, Basal Cell/etiology , Melanoma/etiology , Melanoma/epidemiology , Prospective Studies , Carcinoma, Squamous Cell/epidemiology , Carcinoma, Squamous Cell/etiology , Adult , Sunlight/adverse effects , Risk Factors , Sunbathing/statistics & numerical data , Sunburn/epidemiology , Ultraviolet Rays/adverse effects , Proportional Hazards ModelsABSTRACT
The International Immunosuppression and Transplant Skin Cancer Collaborative (ITSCC) and its European counterpart, Skin Care in Organ Transplant Patients-Europe (SCOPE) are comprised of physicians, surgeons, and scientist who perform integrative collaborative research focused on cutaneous malignancies that arise in solid organ transplant recipients (SOTR) and patients with other forms of long-term immunosuppression. In October 2022, ITSCC held its biennial 4-day scientific symposium in Essex, Massachusetts. This meeting was attended by members of both ITSCC and SCOPE and consisted of specialists including Mohs micrographic and dermatologic oncology surgeons, medical dermatologists, transplant dermatologists, transplant surgeons, and transplant physicians. During this symposium scientific workshop groups focusing on consensus standards for case reporting of retrospective series for invasive squamous cell carcinoma (SCC), defining immunosuppressed patient status for cohort reporting, development of multi-institutional registry for reporting rare tumors, and development of a KERACON clinical trial of interventions after a SOTRs' first cutaneous SCC were developed. The majority of the symposium focused on presentation of the most up to date research in cutaneous malignancy in SOTR and immunosuppressed patients with specific focus on chemoprevention, immunosuppression regimens, immunotherapy in SOTRs, spatial transcriptomics, and the development of cutaneous tumor registries. Here, we present a summary of the most impactful scientific updates presented at the 2022 ITSCC symposium.
Subject(s)
Carcinoma, Squamous Cell , Organ Transplantation , Skin Neoplasms , Humans , Transplant Recipients , Retrospective Studies , Skin Neoplasms/etiology , Immunosuppression Therapy , Carcinoma, Squamous Cell/etiology , Organ Transplantation/adverse effectsABSTRACT
The majority of problematic conditions resulting from dental implant treatment are inflammatory in character, but certain isolated occurrences of primary oral squamous cell carcinoma (OSCC) have been discovered in the area of implants. The goal of this study was to examine whether there is a link between dental implants and the development of OSCC in patients who have a history of a potentially malignant lesion (PML) or malignancy. Using the keywords "carcinoma" AND "dental implants," a search was conducted in the MEDLINE (PubMed), National Center for Biotechnology Information, and Google Scholar databases for case reports and case series in which OSCC was discovered as a primary cancer in the region of dental implants. An initial search identified 260 articles, 247 of which were excluded based on study inclusion or exclusion criteria, leaving 13 articles chosen for inclusion and a total of 30 patients who developed primary oral cancer surrounding osseointegrated titanium-based dental implants. In the studies included in the present review, 22 (73%) of 30 patients with peri-implant cancer had a history of PML or carcinoma. There is no statistical evidence of a direct association between dental implants and OSCC in patients with a history of a PML or malignant lesion. There have been some case reports of OSCC in the region of dental implants in patients with a history of a PML or malignant lesion, but further studies are needed to prove a definitive relationship.
Subject(s)
Carcinoma, Squamous Cell , Dental Implants , Mouth Neoplasms , Humans , Dental Implants/adverse effects , Carcinoma, Squamous Cell/etiology , Carcinoma, Squamous Cell/pathology , Mouth Neoplasms/etiologyABSTRACT
PURPOSE: This updated umbrella review aimed to evaluate the evidence regarding the associations between dietary factors and the risks of esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC). METHODS: The PubMed, Embase, Cochrane Library, and Web of Science databases were searched to identify relevant studies. The quality of the included meta-analyses was evaluated using A MeaSurement Tool to Assess systematic Reviews 2 (AMSTAR 2). For each association, the number of cases, random effects pooled effect size, 95% confidence intervals (CIs), heterogeneity, 95% prediction interval (PrI), small-study effect, and excess significance bias were recalculated to determine the evidence level. RESULTS: We identified 33 meta-analyses describing 58 dietary factors associated with ESCC and 29 meta-analyses describing 38 dietary factors associated with EAC. There was convincing evidence regarding the association of 2 dietary factors (areca nut and high alcohol) with the risk of ESCC. There was highly suggestive evidence regarding the association of only 1 dietary factor (healthy pattern) with the risk of ESCC. There was suggestive evidence regarding the association of 11 dietary factors with the risk of ESCC, including fruit, citrus fruit, vegetables, pickled vegetables, maté tea, moderate alcohol, hot beverages and foods, hot tea, salt, folate, and vitamin B6. There was convincing evidence regarding the association of one dietary factor (vitamin B6) with the risk of EAC. There was suggestive evidence regarding the association of 4 dietary factors with the risk of EAC, including processed meat, dietary fibre, carbohydrate, and vitamin B12. The convincing evidence regarding the associations between dietary factors and the risks of ESCC and EAC remained robust in sensitivity analyses. CONCLUSIONS: This umbrella review highlighted convincing evidence regarding the associations of areca nut and high alcohol with a higher risk of ESCC. Additionally, an association between vitamin B6 and a decreased risk of EAC was observed. Further research is needed to examine the dietary factors with weak evidence regarding their associations with ESCC and EAC.
Subject(s)
Adenocarcinoma , Diet , Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Humans , Esophageal Neoplasms/epidemiology , Esophageal Neoplasms/etiology , Diet/methods , Diet/statistics & numerical data , Diet/adverse effects , Adenocarcinoma/etiology , Adenocarcinoma/epidemiology , Esophageal Squamous Cell Carcinoma/epidemiology , Esophageal Squamous Cell Carcinoma/etiology , Risk Factors , Carcinoma, Squamous Cell/epidemiology , Carcinoma, Squamous Cell/etiologyABSTRACT
Squamous cell carcinoma of the oral cavity presents a significant global health burden, primarily due to risk factors such as tobacco smoking, smokeless tobacco use, heavy alcohol consumption, and betel quid chewing. Common clinical manifestations of oral cavity cancer include visible lesions and sores, often accompanied by pain in advanced stages. Diagnosis relies on a comprehensive assessment involving detailed history, physical examination, and biopsy. Ancillary imaging studies and functional evaluations aid in accurate staging and facilitate treatment planning. Prognostic information is obtained from histopathological factors, such as tumor grade, depth of invasion, lymphovascular invasion, and perineural invasion. Notably, lymph node metastasis, found in approximately half of the patients, carries significant prognostic implications. Effective management necessitates a multidisciplinary approach to optimize patient outcomes. Surgical resection is the backbone of treatment, aimed at complete tumor removal while preserving functional outcomes. Adjuvant therapies, including radiation and chemotherapy, are tailored according to pathological factors. Further work in risk stratification and treatment is necessary to optimize outcomes in squamous cell carcinoma of the oral cavity.
Subject(s)
Carcinoma, Squamous Cell , Mouth Neoplasms , Humans , Mouth Neoplasms/therapy , Mouth Neoplasms/diagnosis , Mouth Neoplasms/etiology , Mouth Neoplasms/pathology , Carcinoma, Squamous Cell/therapy , Carcinoma, Squamous Cell/diagnosis , Carcinoma, Squamous Cell/etiology , Carcinoma, Squamous Cell/pathology , Disease Management , Prognosis , Risk FactorsABSTRACT
PURPOSE: To characterize treatment patterns and real-world clinical outcomes of patients with metastatic non-small cell lung cancer (mNSCLC) who developed progression on an anti-PD-1/anti-PD-L1, herein referred to as anti-PD-(L)1, and platinum-doublet chemotherapy. METHODS: Eligible oncologists/pulmonologists in the United States, Europe (France, Germany, and United Kingdom), and Japan completed electronic case report forms for patients with mNSCLC (no evidence of EGFR/ALK/ROS1 alterations). Eligible patients had disease progression on/after an anti-PD-(L)1 and platinum-doublet chemotherapy (received concurrently or sequentially), initiated a subsequent line of therapy (LOT) between 2017 and 2021, and had an Eastern Cooperative Oncology Group (ECOG) performance status 0-2 at this subsequent LOT initiation (index date). Overall survival (OS), time to treatment discontinuation (TTD), and real-world progression-free survival (rwPFS) after index were assessed using Kaplan-Meier analysis. RESULTS: Overall, 160 physicians (academic, 54.4%; community, 45.6%) provided deidentified data from 487 patient charts (United States, 141; Europe, 218; Japan, 128; at mNSCLC diagnosis: median age 66 years, 64.7% male, 81.3% nonsquamous, 86.2% de novo mNSCLC; at line of interest initiation: 86.0% ECOG 0-1, 39.6% liver metastases, 18.9% brain metastases, 79.1% smoking history). The most common treatment regimens upon progression after anti-PD-(L)1/platinum-doublet chemotherapy were nonplatinum chemotherapy (50.5%), nonplatinum chemotherapy plus vascular endothelial growth factor receptor inhibitor (12.9%), and platinum-doublet chemotherapy (6.6%). Median OS was 8.8 months (squamous, 7.8 months; nonsquamous, 9.5 months). Median TTD was 4.3 months (squamous, 4.1 months; nonsquamous, 4.3 months). Median rwPFS was 5.1 months (squamous, 4.6 months; nonsquamous, 5.4 months). CONCLUSION: In this multiregional, real-world analysis of pooled patient chart data, patients with mNSCLC who had disease progression after anti-PD-(L)1/platinum-doublet chemotherapy had poor clinical outcomes with various treatment regimens, demonstrating an unmet clinical need for effective options after failure on anti-PD-(L)1 and platinum-doublet chemotherapy treatments.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Carcinoma, Squamous Cell , Lung Neoplasms , Humans , Male , United States , Aged , Female , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Platinum/therapeutic use , Japan , Protein-Tyrosine Kinases/therapeutic use , Vascular Endothelial Growth Factor A/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Proto-Oncogene Proteins/therapeutic use , Immunotherapy , Disease Progression , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/etiologyABSTRACT
Immunotherapy has emerged as a promising new treatment modality for head and neck cancer, offering the potential for targeted and effective cancer management. Squamous cell carcinomas pose significant challenges due to their aggressive nature and limited treatment options. Conventional therapies such as surgery, radiation, and chemotherapy often have limited success rates and can have significant side effects. Immunotherapy harnesses the power of the immune system to recognize and eliminate cancer cells, and thus represents a novel approach with the potential to improve patient outcomes. In the management of head and neck squamous cell carcinoma (HNSCC), important contributions are made by immunotherapies, including adaptive cell therapy (ACT) and immune checkpoint inhibitor therapy. In this review, we are focusing on the latter. Immune checkpoint inhibitors target proteins such as programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) to enhance the immune response against cancer cells. The CTLA-4 inhibitors, such as ipilimumab and tremelimumab, have been approved for early-stage clinical trials and have shown promising outcomes in terms of tumor regression and durable responses in patients with advanced HNSCC. Thus, immune checkpoint inhibitor therapy holds promise in overcoming the limitations of conventional therapies. However, further research is needed to optimize treatment regimens, identify predictive biomarkers, and overcome potential resistance mechanisms. With ongoing advancements in immunotherapy, the future holds great potential for transforming the landscape of oral tumor treatment and providing new hope for patients.
Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Humans , Squamous Cell Carcinoma of Head and Neck , Immune Checkpoint Inhibitors , Immunotherapy/adverse effects , Carcinoma, Squamous Cell/etiologyABSTRACT
There is extensive coverage in the existing literature on implant-associated lymphomas like anaplastic large-cell lymphoma, but breast implant-associated squamous cell carcinoma (BIA-SCC) has received limited scholarly attention since its first case in 1992. Thus, this study aims to conduct a qualitative synthesis focused on the underexplored association between breast implants and BIA-SCC. A systematic review was conducted utilizing the PubMed, Web of Science, and Cochrane databases to identify all currently reported cases of BIA-SCC. Additionally, a literature review was performed to identify potential biochemical mechanisms that could lead to BIA-SCC. Studies were vetted for quality using the NIH quality assessment tool. From an initial pool of 246 papers, 11 met the quality criteria for inclusion, examining a total of 14 patients aged between 40 and 81 years. BIA-SCC was found in a diverse range of implants, including those with smooth and textured surfaces, as well as those filled with saline and silicone. The condition notably manifested a proclivity for aggressive clinical progression, as evidenced by a mortality rate approximating 21.4% within a post-diagnostic interval of six months. Our literature review reveals that chronic inflammation, driven by various external factors such as pathogens and implants, can initiate carcinogenesis through epigenetic modifications and immune system alterations. This includes effects from exosomes and macrophage polarization, showcasing potential pathways for the pathogenesis of BIA-SCC. The study highlights the pressing need for further investigation into BIA-SCC, a subject hitherto inadequately addressed in the academic sphere. This necessitates the urgency for early screening and intervention to improve postoperative outcomes. While the review is confined by its reliance on case reports and series, it serves as a valuable reference for future research endeavors.
Subject(s)
Breast Implants , Breast Neoplasms , Carcinoma, Squamous Cell , Adult , Aged , Aged, 80 and over , Female , Humans , Middle Aged , Breast Implants/adverse effects , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/etiology , Carcinoma, Squamous Cell/pathologyABSTRACT
A collaboration of multidisciplinary experts from the European Association of Dermato-Oncology, the European Dermatology Forum, the European Academy of Dermatology and Venereology, and the European Union of Medical Specialists was formed to develop European recommendations on AK diagnosis and treatment, based on current literature and expert consensus. This guideline addresses the epidemiology, diagnostics, risk stratification and treatments in immunocompetent as well as immunosuppressed patients. Actinic keratoses (AK) are potential precursors of cutaneous squamous cell carcinoma (cSCC) and display typical histopathologic and immunohistochemical features of this malignancy in an early stage. They can develop into cSSC in situ and become invasive in a low percentage of cases. AK is the most frequent neoplasia in white populations, frequently occurring within a cancerous field induced by ultraviolet radiation. Since it cannot be predicted, which lesion will progress to cSCC and when treatment is usually recommended. The diagnosis of AK and field cancerization is made by clinical examination. Dermatoscopy, confocal microscopy, optical coherence tomography or line-field confocal-OCT can help in the differential diagnosis of AK and other skin neoplasms. A biopsy is indicated in clinically and/or dermatoscopically suspicious and/or treatment-refractory lesions. The choice of treatment depends on patients' and lesion characteristics. For single non-hyperkeratotic lesions, the treatment can be started upon patient's request with destructive treatments or topical treatments. For multiple lesions, field cancerization treatment is advised with topical treatments and photodynamic therapy. Preventive measures such as sun protection, self-examination and repeated field cancerization treatments of previously affected skin areas in high-risk patients are advised.