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International Journal of Environmental... Dec 2020Oral cancer (OC) is an uncommon malignancy in Western countries, being one of the most common cancers in some high-risk areas of the world. It is a largely preventable... (Review)
Review
Oral cancer (OC) is an uncommon malignancy in Western countries, being one of the most common cancers in some high-risk areas of the world. It is a largely preventable cancer, since most of the different risk factors identified, such as tobacco use, alcohol consumption, and betel nut chewing, are behaviors that increase the likelihood of the disease. Given its high mortality, early diagnosis is of utmost importance. Prevention and the anticipation of diagnosis begin with identification of potentially malignant lesions of the oral mucosa and with local conditions promoting chronic inflammation. Therefore, every lesion must be recognized promptly and treated adequately. The clinical recognition and evaluation of oral mucosal lesions can detect up to 99% of oral cancers/premalignancies. As stated by the World Health Organization, any suspicious lesion that does not subside within two weeks from detection and removal of local causes of irritation must be biopsied. Surgical biopsy remains the gold standard for diagnosis of oral cancer. Adjunctive tools have been developed and studied to help clinicians in the diagnostic pathway, such as toluidine blue vital staining and autofluorescence imaging. In the near future other methods, i.e., identification of salivary markers of progression may help in reducing mortality due to oral cancer.
Topics: Biopsy; Early Detection of Cancer; Humans; Mouth Mucosa; Mouth Neoplasms; Precancerous Conditions
PubMed: 33302498
DOI: 10.3390/ijerph17249160 -
CA: a Cancer Journal For Clinicians 2002In the United States, cancers of the oral cavity and oropharynx represent approximately three percent of all malignancies in men and two percent of all malignancies in... (Review)
Review
In the United States, cancers of the oral cavity and oropharynx represent approximately three percent of all malignancies in men and two percent of all malignancies in women. The American Cancer Society estimates that 28,900 new cases of oral cancer will be diagnosed in 2002, and nearly 7,400 people will die from this disease. Over 90 percent of these tumors are squamous cell carcinomas, which arise from the oral mucosal lining. In spite of the ready accessibility of the oral cavity to direct examination, these malignancies still are often not detected until a late stage, and the survival rate for oral cancer has remained essentially unchanged over the past three decades. The purpose of this article is to review the clinical features of oral cancer and premalignant oral lesions, with an emphasis on early detection.
Topics: Carcinoma, Squamous Cell; Carcinoma, Verrucous; Diagnosis, Differential; Erythroplasia; Humans; Leukoplakia, Oral; Mouth Neoplasms; Neoplasm Staging; Precancerous Conditions; Risk Factors; Nicotiana
PubMed: 12139232
DOI: 10.3322/canjclin.52.4.195 -
World Journal of Gastroenterology Oct 2014Gastric cancer continues to be an important healthcare problem from a global perspective. Most of the cases in the Western world are diagnosed at late stages when the... (Review)
Review
Gastric cancer continues to be an important healthcare problem from a global perspective. Most of the cases in the Western world are diagnosed at late stages when the treatment is largely ineffective. Helicobacter pylori (H. pylori) infection is a well-established carcinogen for gastric cancer. While lifestyle factors are important, the efficacy of interventions in their modification, as in the use of antioxidant supplements, is unconvincing. No organized screening programs can be found outside Asia (Japan and South Korea). Although several screening approaches have been proposed, including indirect atrophy detection by measuring pepsinogen in the circulation, none of them have so far been implemented, and more study data is required to justify any implementation. Mass eradication of H. pylori in high-risk areas tends to be cost-effective, but its adverse effects and resistance remain a concern. Searches for new screening biomarkers, including microRNA and cancer-autoantibody panels, as well as detection of volatile organic compounds in the breath, are in progress. Endoscopy with a proper biopsy follow-up remains the standard for early detection of cancer and related premalignant lesions. At the same time, new advanced high-resolution endoscopic technologies are showing promising results with respect to diagnosing mucosal lesions visually and targeting each biopsy. New histological risk stratifications (classifications), including OLGA and OLGIM, have recently been developed. This review addresses the current means for gastric cancer primary and secondary prevention, the available and emerging methods for screening, and new developments in endoscopic detection of early lesions of the stomach.
Topics: Biopsy; Early Detection of Cancer; Gastroscopy; Humans; Life Style; Neoplasm Staging; Precancerous Conditions; Predictive Value of Tests; Preventive Health Services; Risk Assessment; Risk Factors; Risk Reduction Behavior; Stomach Neoplasms
PubMed: 25320521
DOI: 10.3748/wjg.v20.i38.13842 -
Human Reproduction Update Mar 2017Endometrial hyperplasia (EH) is a uterine pathology representing a spectrum of morphological endometrial alterations. It is predominantly characterized by an increase in... (Review)
Review
BACKGROUND
Endometrial hyperplasia (EH) is a uterine pathology representing a spectrum of morphological endometrial alterations. It is predominantly characterized by an increase in the endometrial gland-to-stroma ratio when compared to normal proliferative endometrium. The clinical significance of EH lies in the associated risk of progression to endometrioid endometrial cancer (EC) and 'atypical' forms of EH are regarded as premalignant lesions. Traditional histopathological classification systems for EH exhibit wide and varying degrees of diagnostic reproducibility and, as a consequence, standardized patient management can be challenging.
OBJECTIVE AND RATIONALE
EC is the most common gynaecological malignancy in developed countries. The incidence of EC is rising, with alarming increases described in the 40-44-year-old age group. This review appraises the current EH classification systems used to stratify women at risk of malignant progression to EC. In addition, we summarize the evidence base regarding the use of immunohistochemical biomarkers for EH and discuss an emerging role for genomic analysis.
SEARCH METHODS
PubMed, Medline and the Cochrane Database were searched for original peer-reviewed primary and review articles, from January 2000 to January 2016. The following search terms were used: 'endometrial hyperplasia', 'endometrial intraepithelial neoplasia', 'atypical hyperplasia', 'complex atypical hyperplasia', 'biomarker', 'immunohistochemistry', 'progression', 'genomic', 'classification' and 'stratification'.
OUTCOMES
Recent changes to EH classification reflect our current understanding of the genesis of endometrioid ECs. The concept of endometrial intraepithelial neoplasia (EIN) as a mutationally activated, monoclonal pre-malignancy represents a fundamental shift from the previously held notion that unopposed oestrogenic stimulation causes ever-increasing hyperplastic proliferation, with accumulating cytological atypia that imperceptibly leads to the development of endometrioid EC. Our review highlights several key biomarker candidates that have been described as both diagnostic tools for EH and markers of progression to EC. We propose that, moving forwards, a 'panel' approach of combinations of the immunohistochemical biomarkers described in this review may be more informative since no single candidate can currently fill the entire role.
WIDER IMPLICATIONS
EC has historically been considered a predominantly postmenopausal disease. Owing in part to the current unprecedented rates of obesity, we are starting to see signs of a shift towards a rising incidence of EC amongst pre- and peri-menopausal woman. This creates unique challenges both diagnostically and therapeutically. Furthering our understanding of the premalignant stages of EC development will allow us to pursue earlier diagnosis and facilitate appropriate stratification of women at risk of developing EC, permitting timely and appropriate therapeutic interventions.
Topics: Biomarkers; Disease Progression; Endometrial Hyperplasia; Endometrial Neoplasms; Endometrium; Female; Humans; Precancerous Conditions; Reproducibility of Results; Risk
PubMed: 27920066
DOI: 10.1093/humupd/dmw042 -
Cold Spring Harbor Perspectives in... Dec 2017Where does cancer come from? Although the cell-of-origin is difficult to pinpoint, cancer clones harbor information about their clonal ancestries. In an effort to find... (Review)
Review
Where does cancer come from? Although the cell-of-origin is difficult to pinpoint, cancer clones harbor information about their clonal ancestries. In an effort to find cells before they evolve into a life-threatening cancer, physicians currently diagnose premalignant diseases at frequencies that substantially exceed those of clinical cancers. Cancer risk prediction relies on our ability to distinguish between which premalignant features will lead to cancer mortality and which are characteristic of inconsequential disease. Here, we review the evolution of cancer from premalignant disease, and discuss the concept that even phenotypically normal cell progenies inherently gain more malignant potential with age. We describe the hurdles of prognosticating cancer risk in premalignant disease by making reference to the underlying continuous and multivariate natures of genotypes and phenotypes and the particular challenge inherent in defining a cell lineage as "cancerized."
Topics: Animals; Cell Lineage; Cell Transformation, Neoplastic; Clonal Evolution; Humans; Phenotype; Precancerous Conditions
PubMed: 28490542
DOI: 10.1101/cshperspect.a026542 -
Cold Spring Harbor Perspectives in... Apr 2020Clonal hematopoiesis (CH) arises when mutations in the hematopoietic system confer a fitness advantage to specific clones, thereby favoring their disproportionate... (Review)
Review
Clonal hematopoiesis (CH) arises when mutations in the hematopoietic system confer a fitness advantage to specific clones, thereby favoring their disproportionate growth. The presence of CH increases with age and environmental exposures such as cytotoxic chemotherapy or radiotherapy. The most frequent mutations occur in epigenetic regulators, such as , , and , leading to dysregulation of tumor suppressor function, pathogen response, and inflammation. These dysregulated processes elevate risk of overall mortality, cardiovascular disease, and eventual hematologic malignancy (HM). CH is likely acting as an initiating event leading to HM when followed by cooperating mutations. However, further evidence suggests that CH exerts a bystander influence through its pro-inflammatory properties. Delineating the mechanisms that lead to the onset and expansion of CH as well as its contribution to risk of HM is crucial to defining a management and intervention strategy. In this review, we discuss the potential causes, consequences, technical considerations, and possible management strategies for CH in the context of HMs and pre-HMs.
Topics: Animals; Clonal Hematopoiesis; Hematologic Neoplasms; Hematopoietic Stem Cells; Humans; Leukemia; Mutation; Neoplasm Proteins; Precancerous Conditions
PubMed: 31615870
DOI: 10.1101/cshperspect.a035675 -
Digestive Diseases (Basel, Switzerland) 2022Esophageal conditions result in significant morbidity and mortality worldwide. There is growing enthusiasm for discerning the role of microbiome in esophageal diseases.... (Review)
Review
BACKGROUND
Esophageal conditions result in significant morbidity and mortality worldwide. There is growing enthusiasm for discerning the role of microbiome in esophageal diseases. Conceivably, the focus has been on examining the role of local microbiome in esophageal diseases although this is somewhat limited by the invasive approach required to sample the esophageal tissue. Given the ease of sampling the oral cavity combined with the advances in genomic techniques, there is immense interest in discovering the role of the oral microbiome in esophageal conditions.
SUMMARY
In this review, we aim to discuss the current evidence highlighting the association between the oral microbiome and esophageal diseases. In particular, we have focused on summarizing the alterations in oral microbiome associated with malignant, premalignant, and benign esophageal cancers, inflammatory and infectious conditions, and esophageal dysmotility diseases. Identifying alterations in the oral microbiome is a key to advancing our understanding of the etiopathogenesis and progression of esophageal diseases, promoting novel diagnostics, and laying the foundation for personalized treatment approaches.
KEY MESSAGES
Further studies are needed to unravel the mechanisms by which the oral microbiome influences the development and progression of esophageal diseases, as well as to investigate whether alterations in the oral microbiome can impact the natural history of various esophageal diseases.
Topics: Barrett Esophagus; Esophageal Diseases; Esophageal Neoplasms; Humans; Microbiota; Precancerous Conditions
PubMed: 34315165
DOI: 10.1159/000517736 -
EBioMedicine Jun 2023Cervical cancer is the fourth leading cause of mortality among gynecological malignancies. However, the identification of cervical cancer stem cells remains unclear.
BACKGROUND
Cervical cancer is the fourth leading cause of mortality among gynecological malignancies. However, the identification of cervical cancer stem cells remains unclear.
METHODS
We performed single-cell mRNA sequencing on ∼122,400 cells from 20 cervical biopsies, including 5 healthy controls, 4 high-grade intraepithelial neoplasias, 5 microinvasive carcinomas of the cervix, and 6 invasive cervical squamous carcinomas. Bioinformatic results were validated by multiplex immunohistochemistry (mIHC) in cervical cancer tissue microarrays (TMA) (n = 85).
FINDINGS
We identified cervical cancer stem cells and highlighted the functional changes in cervical stem cells during malignant transformation. The original non-malignant stem cell properties (characterized by high proliferation) gradually diminished, whereas the tumor stem cell properties (characterized by epithelial-mesenchymal transformation and invasion) were enhanced. The mIHC results of our TMA cohort confirmed the existence of stem-like cells and indicated that cluster correlated with neoplastic recurrence. Subsequently, we investigated malignant and immune cell heterogeneity in the cervical multicellular ecosystem across different disease stages. We observed global upregulation of interferon responses in the cervical microenvironment during lesion progression.
INTERPRETATION
Our results provide more insights into cervical premalignant and malignant lesion microenvironments.
FUNDING
This research was supported by the Guangdong Provincial Natural Science Foundation of China (2023A1515010382), Grant 2021YFC2700603 from the National Key Research & Development Program of China and the Hubei Provincial Natural Science Foundation of China (2022CFB174 and 2022CFB893).
Topics: Female; Humans; Uterine Cervical Neoplasms; Cervix Uteri; Uterine Cervical Dysplasia; Ecosystem; Transcriptome; Neoplasm Recurrence, Local; Precancerous Conditions; Carcinoma, Squamous Cell; Neoplastic Stem Cells; Tumor Microenvironment
PubMed: 37224771
DOI: 10.1016/j.ebiom.2023.104612 -
Cancer Prevention Research... Jul 2023Histologically normal human tissues accumulate significant mutational burden with age. The extent and spectra of mutagenesis are comparable both in rapidly proliferating... (Review)
Review
Histologically normal human tissues accumulate significant mutational burden with age. The extent and spectra of mutagenesis are comparable both in rapidly proliferating and post-mitotic tissues and in stem cells compared with their differentiated progeny. Some of these mutations provide increased fitness, giving rise to clones which, at times, can replace the entire surface area of tissues. Compared with cancer, somatic mutations in histologically normal tissues are primarily single-nucleotide variations. Interestingly though, the presence of these mutations and positive clonal selection in isolation remains a poor indicator of potential future cancer transformation in solid tissues. Common clonally expanded mutations in histologically normal tissues also do not always represent the most frequent early mutations in cancers of corresponding tissues, indicating differences in selection pressures. Preliminary evidence implies that stroma and immune system co-evolve with age, which may impact selection dynamics. In this review, we will explore the mutational landscape of histologically normal and premalignant human somatic tissues in detail and discuss cell-intrinsic and environmental factors that can determine the fate of positively selected mutations within them. Precisely pinpointing these determinants of cancer transformation would aid development of early cancer interventional and prevention strategies.
Topics: Humans; Precancerous Conditions; Mutation; Clone Cells; Cell Transformation, Neoplastic; Clonal Evolution
PubMed: 36930945
DOI: 10.1158/1940-6207.CAPR-22-0469 -
Proceedings of the American Thoracic... May 2012Lung cancer is the leading cause of cancer death in the United States, and the majority of diagnoses are made in former smokers. Although avoidance of tobacco abuse and...
Lung cancer is the leading cause of cancer death in the United States, and the majority of diagnoses are made in former smokers. Although avoidance of tobacco abuse and smoking cessation clearly will have the greatest impact on lung cancer development, effective chemoprevention could prove to be more effective than treatment of established, advanced-stage disease. Chemoprevention is the use of dietary or pharmaceutical agents to reverse or block the carcinogenic process and has been successfully applied to common malignancies other than lung (including recent reports on the prevention of breast cancer in high-risk individuals). Despite previous studies in lung cancer chemoprevention failing to identify effective agents, our ability to define the highest-risk populations and the understanding of lung tumor and premalignant biology continue to make advances. Squamous cell carcinogenesis in the bronchial epithelium starts with normal epithelium and progresses through hyperplasia, metaplasia, dysplasia, and carcinoma in situ to invasive cancer. Precursor lesions also have been identified for adenocarcinoma, and these premalignant lesions are targeted by chemopreventive agents in current and future trials. Chemopreventive agents can currently only be recommended as part of well-designed clinical trials, and multiple trials have recently been completed or are enrolling subjects.
Topics: Biomarkers, Tumor; Chemoprevention; Clinical Trials as Topic; Humans; Lung Neoplasms; Precancerous Conditions
PubMed: 22550242
DOI: 10.1513/pats.201107-038MS