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1.
BMC Womens Health ; 24(1): 271, 2024 May 03.
Article in English | MEDLINE | ID: mdl-38702683

ABSTRACT

BACKGROUND: Precancerous cervical lesions develop in the transformation zone of the cervix and progress through stages known as cervical intraepithelial neoplasia (CIN) 1, 2, and 3. If untreated, CIN2 or CIN3 can lead to cervical cancer. The determinants of cervical precancerous lesions are not well documented in Ethiopia. Therefore, this study aims to find the determinants of cervical precancerous lesions among women screened for cervical cancer at public health facilities. METHODS: A study conducted from January to April 2020 involved 216 women, consisting of 54 cases (positive for VIA during cervical cancer screening) and 162 controls (negative for VIA). It focused on women aged 30 to 49 undergoing cervical cancer screening. Multivariable logistic regression analysis assessed the link between precancerous lesions and different risk factors, considering a significance level of p < 0.05. RESULTS: Women who used oral contraceptives for a duration exceeding five years showed a nearly fivefold increase in the likelihood of developing precancerous lesions (Adjusted Odds Ratio (AOR) = 4.75; 95% CI: 1.48, 15.30). Additionally, early age at first sexual intercourse (below 15 years) elevated the odds of developing precancerous lesions fourfold (AOR = 3.77; 95% CI: 1.46, 9.69). Furthermore, women with HIV seropositive results and a prior history of sexually transmitted infections (STIs) had 3.4 times (AOR = 3.45; 95% CI: 1.29, 9.25) and 2.5 times (AOR = 2.58; 95% CI: 1.10, 6.09) higher odds of developing cervical precancerous lesions compared to their counterparts. CONCLUSION: In conclusion, women who have used oral contraceptives for over five years, started sexual activity before the age of 15 and have a history of sexually transmitted infections, including HIV, are at higher risk of developing precancerous cervical lesions. Targeted intervention strategies aimed at promoting behavioural change to prevent early sexual activity and STIs are crucial for avoiding cervical precancerous lesions. It is crucial to introduce life-course principles for female adolescents early on, acknowledging the potential to prevent and control precancerous lesions at critical stages in life, from early adolescence to adulthood, encompassing all developmental phases.


Subject(s)
Early Detection of Cancer , Precancerous Conditions , Uterine Cervical Dysplasia , Uterine Cervical Neoplasms , Humans , Female , Ethiopia/epidemiology , Adult , Uterine Cervical Neoplasms/diagnosis , Uterine Cervical Neoplasms/epidemiology , Case-Control Studies , Middle Aged , Early Detection of Cancer/methods , Early Detection of Cancer/statistics & numerical data , Precancerous Conditions/diagnosis , Precancerous Conditions/epidemiology , Uterine Cervical Dysplasia/epidemiology , Uterine Cervical Dysplasia/diagnosis , Risk Factors , Health Facilities/statistics & numerical data
2.
J Med Virol ; 96(5): e29521, 2024 May.
Article in English | MEDLINE | ID: mdl-38727013

ABSTRACT

Methylation panels, tools for investigating epigenetic changes associated with diseases like cancer, can identify DNA methylation patterns indicative of disease, providing diagnostic or prognostic insights. However, the application of methylation panels focusing on the sex-determining region Y-box 1 (SOX1) and paired box gene 1 (PAX1) genes for diagnosing cervical lesions is under-researched. This study aims to examine the diagnostic performance of PAX1/SOX1 gene methylation as a marker for cervical precancerous lesions and its potential application in triage diagnosis. From September 2022 to April 2023, 181 patients with abnormal HPV-DNA tests or cytological exam results requiring colposcopy were studied at Hubei Maternal and Child Health Hospital, China. Data were collected from colposcopy, cytology, HPV-DNA tests, and PAX1/SOX1 methylation detection. Patients were categorized as control, cervical intraepithelial neoplasia Grade 1 (CIN1), Grade 2 (CIN2), Grade 3 (CIN3), and cervical cancer (CC) groups based on histopathology. We performed HPV testing, liquid-based cytology, and PAX1/SOX1 gene methylation testing. We evaluated the diagnostic value of methylation detection in cervical cancer using DNA methylation positivity rate, sensitivity, specificity, and area under the curve (AUC), and explored its potential for triage diagnosis. PAX1/SOX1 methylation positivity rates were: control 17.1%, CIN1 22.5%, CIN2 100.0%, CIN3 90.0%, and CC 100.0%. The AUC values for PAX1 gene methylation detection in diagnosing CIN1+, CIN2+, and CIN3+ were 0.52 (95% confidence interval [CI]: 0.43-0.62), 0.88 (95% CI: 0.80-0.97), and 0.88 (95% CI: 0.75-1.00), respectively. Corresponding AUC values for SOX1 gene methylation detection were 0.47 (95% CI: 0.40-0.58), 0.80 (95% CI: 0.68-0.93), and 0.92 (95% CI: 0.811-1.00), respectively. In HPV16/18-negative patients, methylation detection showed sensitivity of 32.4% and specificity of 83.7% for CIN1+. For CIN2+ and CIN3+, sensitivity was all 100%, with specificities of 83.0% and 81.1%. Among the patients who underwent colposcopy examination, 166 cases had cytological examination results ≤ASCUS, of which 37 cases were positive for methylation, and the colposcopy referral rate was 22.29%. PAX1/SOX1 gene methylation detection exhibits strong diagnostic efficacy for cervical precancerous lesions and holds significant value in triage diagnosis.


Subject(s)
DNA Methylation , Paired Box Transcription Factors , Papillomavirus Infections , SOXB1 Transcription Factors , Triage , Uterine Cervical Dysplasia , Uterine Cervical Neoplasms , Humans , Female , Uterine Cervical Neoplasms/diagnosis , Uterine Cervical Neoplasms/genetics , SOXB1 Transcription Factors/genetics , Adult , Uterine Cervical Dysplasia/diagnosis , Uterine Cervical Dysplasia/genetics , Uterine Cervical Dysplasia/virology , Middle Aged , Triage/methods , Paired Box Transcription Factors/genetics , Papillomavirus Infections/diagnosis , Papillomavirus Infections/virology , Papillomavirus Infections/genetics , Sensitivity and Specificity , Biomarkers, Tumor/genetics , China , Precancerous Conditions/diagnosis , Precancerous Conditions/genetics , Young Adult , Early Detection of Cancer/methods , Colposcopy
3.
BMC Gastroenterol ; 24(1): 170, 2024 May 17.
Article in English | MEDLINE | ID: mdl-38760726

ABSTRACT

BACKGROUND: Low grade intraepithelial neoplasia (LGIN) and high grade intraepithelial neoplasia (HGIN) are potential precancerous lesion of gastric neoplasms. Endoscopic submucosal dissection (ESD) is the first option for the treatment of precancerous lesion and early gastric cancer (EGC). Traction is an effective method to improve efficiency, and reduce complications during ESD. In this study, we shared a useful traction method using the clip-and-snare method with a pre-looping technique (CSM-PLT) for precancerous lesion and EGC. METHODS: We retrospectively analyzed patients received ESD combined with CSM-PLT or conventional ESD from June 2018 to December 2021 in Shenzhen People's hospital. The primary outcome was resection speed. RESULTS: Forty-two patients were enrolled in ESD combined with CSM-PLT group and sixty-five patients in conventional ESD group respectively. Baseline characteristics were comparable among two groups (P>0.05). There were no significant differences in terms of R0 resection rate, en bloc resection rate (97.6% vs. 98.5%, P = 1.000 and 97.6% vs. 96.9%, P = 1.000, respectively), operation costs (933.7 (644.1-1102.4) dollars vs. 814.7 (614.6-988.3) dollars, P = 0.107), and hospital stays (8.0 ± 3.1 days vs. 7.3 ± 3.2 days, P = 0.236). In addition, no significant difference was observed with respect to complications (P>0.05). However, the resection speed of ESD combined with CSM-PLT was faster than that of conventional ESD (11.3 (9.4-14.9) mm2/min vs. 8.0 (5.8-10.9) mm2/min, P < 0.001), particularly lesions located in anterior wall and lesser curvature. In addition, the association between ESD combined with CSM-PLT and resection speed was still supported after propensity matching scores (PMS). CONCLUSIONS: CSM-PLT can help to improve ESD efficiency without reducing the en bloc resection rate or increasing the incidence of complications.


Subject(s)
Endoscopic Mucosal Resection , Precancerous Conditions , Stomach Neoplasms , Humans , Male , Retrospective Studies , Female , Stomach Neoplasms/surgery , Stomach Neoplasms/pathology , Middle Aged , Endoscopic Mucosal Resection/methods , Endoscopic Mucosal Resection/adverse effects , Precancerous Conditions/surgery , Precancerous Conditions/pathology , Aged , Treatment Outcome , Operative Time , Carcinoma in Situ/surgery , Carcinoma in Situ/pathology
4.
J Pak Med Assoc ; 74(5): 852-856, 2024 May.
Article in English | MEDLINE | ID: mdl-38783429

ABSTRACT

Objective: To determine the expression of podoplanin, and to correlate it with histopathological grades in oral epithelial dysplasia and oral squamous cell carcinoma cases. METHODS: The retrospective, analytical, cross-sectional study was conducted at the City Laboratory, Peshawar, Pakistan, and comprised specimen block data of histologically diagnosed cases of oral benign lesions, dysplastic lesions and oral squamous cell carcinoma from January 2017 to August 2021. Two sections (4um) were cut from each specimen block for Haematoxylin and Eosin staining and immunohistochemistry. The slides were re-evaluated by two pathologists for confirmation of the diagnosis, and podoplanin marker was applied to cases selected using immunohistochemistry. Data was analysed using SPSS 22. RESULTS: Of the 80 cases identified, 68(85%) were analysed. There were 20(29.4%) benign cases; 11(55%) females and 9(45%) males with mean age 39.90±16.23 years, 20(29.4%) oral dysplastic cases; 14(70%) males and 6(30%) females with mean age 57.75±12.02 years, and 28(41.2%) oral squamous cell carcinoma cases; 17(61%) males and 11(39%) females with mean age 50.55±14.80 years. Podoplanin expression in oral epithelial dysplasia cases was significant (p=0.028), while it was not significant in the other 2 groups (p>0.05). CONCLUSIONS: Podoplanin when used along with histopathological evaluation could aid as an adjuvant technique in the diagnosis and grading of oral epithelial dysplasia.


Subject(s)
Membrane Glycoproteins , Mouth Neoplasms , Humans , Female , Male , Membrane Glycoproteins/metabolism , Mouth Neoplasms/pathology , Mouth Neoplasms/metabolism , Middle Aged , Adult , Cross-Sectional Studies , Retrospective Studies , Aged , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/metabolism , Precancerous Conditions/pathology , Precancerous Conditions/metabolism , Pakistan/epidemiology , Young Adult , Mouth Mucosa/pathology , Mouth Mucosa/metabolism , Neoplasm Grading , Biomarkers, Tumor/metabolism , Immunohistochemistry
5.
Nat Commun ; 15(1): 3700, 2024 May 02.
Article in English | MEDLINE | ID: mdl-38697989

ABSTRACT

Detecting early-stage esophageal squamous cell carcinoma (ESCC) and precancerous lesions is critical for improving survival. Here, we conduct whole-genome bisulfite sequencing (WGBS) on 460 cfDNA samples from patients with non-metastatic ESCC or precancerous lesions and matched healthy controls. We develop an expanded multimodal analysis (EMMA) framework to simultaneously identify cfDNA methylation, copy number variants (CNVs), and fragmentation markers in cfDNA WGBS data. cfDNA methylation markers are the earliest and most sensitive, detectable in 70% of ESCCs and 50% of precancerous lesions, and associated with molecular subtypes and tumor microenvironments. CNVs and fragmentation features show high specificity but are linked to late-stage disease. EMMA significantly improves detection rates, increasing AUCs from 0.90 to 0.99, and detects 87% of ESCCs and 62% of precancerous lesions with >95% specificity in validation cohorts. Our findings demonstrate the potential of multimodal analysis of cfDNA methylome for early detection and monitoring of molecular characteristics in ESCC.


Subject(s)
Biomarkers, Tumor , DNA Copy Number Variations , DNA Methylation , Early Detection of Cancer , Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Precancerous Conditions , Humans , Esophageal Squamous Cell Carcinoma/genetics , Esophageal Squamous Cell Carcinoma/diagnosis , Precancerous Conditions/genetics , Precancerous Conditions/diagnosis , Precancerous Conditions/pathology , Esophageal Neoplasms/genetics , Esophageal Neoplasms/diagnosis , Esophageal Neoplasms/pathology , Male , Early Detection of Cancer/methods , Female , Biomarkers, Tumor/genetics , Middle Aged , Aged , Epigenome , Cell-Free Nucleic Acids/genetics , Cell-Free Nucleic Acids/blood , Whole Genome Sequencing/methods , Tumor Microenvironment/genetics
6.
PLoS One ; 19(5): e0303421, 2024.
Article in English | MEDLINE | ID: mdl-38743709

ABSTRACT

BACKGROUND AND AIMS: Gastric intestinal metaplasia is a precancerous disease, and a timely diagnosis is essential to delay or halt cancer progression. Artificial intelligence (AI) has found widespread application in the field of disease diagnosis. This study aimed to conduct a comprehensive evaluation of AI's diagnostic accuracy in detecting gastric intestinal metaplasia in endoscopy, compare it to endoscopists' ability, and explore the main factors affecting AI's performance. METHODS: The study followed the PRISMA-DTA guidelines, and the PubMed, Embase, Web of Science, Cochrane, and IEEE Xplore databases were searched to include relevant studies published by October 2023. We extracted the key features and experimental data of each study and combined the sensitivity and specificity metrics by meta-analysis. We then compared the diagnostic ability of the AI versus the endoscopists using the same test data. RESULTS: Twelve studies with 11,173 patients were included, demonstrating AI models' efficacy in diagnosing gastric intestinal metaplasia. The meta-analysis yielded a pooled sensitivity of 94% (95% confidence interval: 0.92-0.96) and specificity of 93% (95% confidence interval: 0.89-0.95). The combined area under the receiver operating characteristics curve was 0.97. The results of meta-regression and subgroup analysis showed that factors such as study design, endoscopy type, number of training images, and algorithm had a significant effect on the diagnostic performance of AI. The AI exhibited a higher diagnostic capacity than endoscopists (sensitivity: 95% vs. 79%). CONCLUSIONS: AI-aided diagnosis of gastric intestinal metaplasia using endoscopy showed high performance and clinical diagnostic value. However, further prospective studies are required to validate these findings.


Subject(s)
Artificial Intelligence , Metaplasia , Humans , Metaplasia/diagnosis , Metaplasia/pathology , Stomach Neoplasms/diagnosis , Stomach Neoplasms/pathology , Sensitivity and Specificity , Precancerous Conditions/diagnosis , Precancerous Conditions/pathology , ROC Curve , Stomach/pathology
7.
Stomatologiia (Mosk) ; 103(2): 5-11, 2024.
Article in Russian | MEDLINE | ID: mdl-38741528

ABSTRACT

OBJECTIVE: The aim of the study. Improving the efficiency of diagnosis and detailing the features of the clinic of «potentially malignant¼ diseases of the oral mucosa. MATERIALS AND METHODS: Clinical and laboratory examination of 124 patients of the department of oral mucosa diseases aged 35 to 80 years, among whom there were 75 women and 49 men, with diseases such as erythroplakia - 12 patients, verrucous leukoplakia - 52 patients, erosive form of leukoplakia - 35 patients, cheilitis Manganotti - 25 patients. Histological and immunohistochemical methods of investigation were used as diagnostics. To assess the proliferative activity of epithelial cells, the determination of the Ki-67 index was used. The synthesis of keratin 15 (K15) in epithelial layers was determined as a diagnostic criterion for the severity of neoplasia. The expression of human papillomavirus type 16 (HPV 16) antigens and p16INK4a protein in epithelial cells was studied, as well as the expression of p53 protein. RESULTS: A high prevalence of p53 mutations was observed in patients with erythroplakia. In leukoplakia, the expression of the Ki-67 protein was detected in the cell nuclei in both the basal and parabasal layers of the multilayer squamous epithelium, in 77% of cases, the expression of the p16INK4a protein in the epithelial nuclei with varying degrees of dysplastic changes was noted, and a positive reaction to HPV16 was also observed in the cell nuclei and cytoplasm of epithelial cells in the basal, parabasal and spiny epithelial layers. The appearance of K15 in the cytoplasm of cells above the basal layer with abrasive precancerous cheilitis was found in 48% of cases. CONCLUSION: To diagnose early manifestations of neoplastic processes in «potentially malignant¼ diseases of the oral mucosa, it is necessary to use both classical histological and immunohistochemical methods of investigation with various markers.


Subject(s)
Ki-67 Antigen , Mouth Mucosa , Precancerous Conditions , Humans , Middle Aged , Male , Female , Aged , Adult , Mouth Mucosa/pathology , Aged, 80 and over , Ki-67 Antigen/analysis , Precancerous Conditions/pathology , Precancerous Conditions/diagnosis , Mouth Neoplasms/pathology , Mouth Neoplasms/diagnosis , Leukoplakia, Oral/pathology , Leukoplakia, Oral/diagnosis , Tumor Suppressor Protein p53/analysis , Tumor Suppressor Protein p53/metabolism , Cheilitis/pathology , Cheilitis/diagnosis , Human papillomavirus 16/isolation & purification , Human papillomavirus 16/genetics , Cyclin-Dependent Kinase Inhibitor p16/analysis , Cyclin-Dependent Kinase Inhibitor p16/metabolism , Erythroplasia/pathology , Erythroplasia/diagnosis
8.
Head Neck Pathol ; 18(1): 38, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38727841

ABSTRACT

INTRODUCTION: Oral epithelial dysplasia (OED) is a precancerous histopathological finding which is considered the most important prognostic indicator for determining the risk of malignant transformation into oral squamous cell carcinoma (OSCC). The gold standard for diagnosis and grading of OED is through histopathological examination, which is subject to inter- and intra-observer variability, impacting accurate diagnosis and prognosis. The aim of this review article is to examine the current advances in digital pathology for artificial intelligence (AI) applications used for OED diagnosis. MATERIALS AND METHODS: We included studies that used AI for diagnosis, grading, or prognosis of OED on histopathology images or intraoral clinical images. Studies utilizing imaging modalities other than routine light microscopy (e.g., scanning electron microscopy), or immunohistochemistry-stained histology slides, or immunofluorescence were excluded from the study. Studies not focusing on oral dysplasia grading and diagnosis, e.g., to discriminate OSCC from normal epithelial tissue were also excluded. RESULTS: A total of 24 studies were included in this review. Nineteen studies utilized deep learning (DL) convolutional neural networks for histopathological OED analysis, and 4 used machine learning (ML) models. Studies were summarized by AI method, main study outcomes, predictive value for malignant transformation, strengths, and limitations. CONCLUSION: ML/DL studies for OED grading and prediction of malignant transformation are emerging as promising adjunctive tools in the field of digital pathology. These adjunctive objective tools can ultimately aid the pathologist in more accurate diagnosis and prognosis prediction. However, further supportive studies that focus on generalization, explainable decisions, and prognosis prediction are needed.


Subject(s)
Artificial Intelligence , Mouth Neoplasms , Precancerous Conditions , Humans , Precancerous Conditions/pathology , Precancerous Conditions/diagnosis , Mouth Neoplasms/pathology , Mouth Neoplasms/diagnosis , Mouth Mucosa/pathology
9.
PLoS One ; 19(5): e0302204, 2024.
Article in English | MEDLINE | ID: mdl-38709808

ABSTRACT

BACKGROUND AND OBJECTIVE: Barrett's esophagus (BE) is a precancerous condition that has the potential to develop into esophageal cancer (EC). Currently, there is a wide range of management options available for individuals at different pathological stages in Barrett's esophagus (BE). However, there is currently a lack of knowledge regarding their comparative efficacy. To address this gap, we conducted a network meta-analysis of published randomized controlled trials to examine the comparative effectiveness of all regimens. METHODS: Data extracted from eligible randomized controlled trials were utilized in a Bayesian network meta-analysis to examine the relative effectiveness of BE's treatment regimens and determine their ranking in terms of efficacy. The ranking probability for each regimen was assessed using the surfaces under cumulative ranking values. The outcomes under investigation were complete ablation of BE, neoplastic progression of BE, and complete eradication of dysplasia. RESULTS: We identified twenty-three RCT studies with a total of 1675 participants, and ten different interventions. Regarding complete ablation of non-dysplastic BE, the comparative effectiveness ranking indicated that argon plasma coagulation (APC) was the most effective regimen, with the highest SUCRA value, while surveillance and PPI/H2RA were found to be the least efficacious regimens. For complete ablation of BE with low-grade dysplasia, high-grade dysplasia, or esophageal cancer, photodynamic therapy (PDT) had the highest SUCRA value of 94.1%, indicating it as the best regimen. Additionally, for complete eradication of dysplasia, SUCRA plots showed a trend in ranking PDT as the highest with a SUCRA value of 91.2%. Finally, for neoplastic progression, radiofrequency ablation (RFA) and surgery were found to perform significantly better than surveillance. The risk of bias assessment revealed that 6 studies had an overall high risk of bias. However, meta-regression with risk of bias as a covariate did not indicate any influence on the model. In terms of the Confidence in Network Meta-Analysis evaluation, a high level of confidence was found for all treatment comparisons. CONCLUSION: Endoscopic surveillance alone or PPI/H2RA alone may not be sufficient for managing BE, even in cases of non-dysplastic BE. However, APC has shown excellent efficacy in treating non-dysplastic BE. For cases of BE with low-grade dysplasia, high-grade dysplasia, or esophageal cancer, PDT may be the optimal intervention as it can induce regression of BE metaplasia and prevent future progression of BE to dysplasia and EC.


Subject(s)
Barrett Esophagus , Esophageal Neoplasms , Network Meta-Analysis , Barrett Esophagus/pathology , Barrett Esophagus/therapy , Barrett Esophagus/surgery , Humans , Esophageal Neoplasms/pathology , Esophageal Neoplasms/therapy , Esophageal Neoplasms/surgery , Randomized Controlled Trials as Topic , Bayes Theorem , Precancerous Conditions/pathology , Precancerous Conditions/surgery , Precancerous Conditions/therapy , Treatment Outcome , Argon Plasma Coagulation , Disease Progression
11.
Genes (Basel) ; 15(5)2024 May 14.
Article in English | MEDLINE | ID: mdl-38790249

ABSTRACT

Transposable elements (TEs) are characterized by their ability to change their genomic position. Through insertion or recombination leading to deletions and other chromosomal aberrations, they can cause genetic instability. The extent to which they thereby exert regulatory influence on cellular functions is unclear. To better characterize TEs in processes such as carcinogenesis, we used the well-established Xiphophorus melanoma model. By transcriptome sequencing, we show that an increasing total number in transposons correlates with progression of malignancy in melanoma samples from Xiphophorus interspecific hybrids. Further, by comparing the presence of TEs in the parental genomes of Xiphophorus maculatus and Xiphophorus hellerii, we could show that even in closely related species, genomic location and spectrum of TEs are considerably different.


Subject(s)
Cyprinodontiformes , DNA Transposable Elements , Melanoma , Animals , DNA Transposable Elements/genetics , Cyprinodontiformes/genetics , Melanoma/genetics , Melanoma/pathology , Transcriptome , Gene Expression Regulation, Neoplastic , Precancerous Conditions/genetics , Precancerous Conditions/pathology
12.
Biotech Histochem ; 99(3): 174-181, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38736402

ABSTRACT

Laminin receptor 1 (LAMR) may have a role in the progression of premalignant squamous epithelial lesions to cervical cancer. Therefore, we aimed to investigate the expression of laminin receptor 1 (LAMR) in normal, premalignant, and malignant tissues of the uterine cervix. Paraffin blocks of 129 specimens with the diagnoses of normal cervical tissue (n = 33), cervical intraepithelial neoplasia (CIN) 1 (n = 30), CIN 2 (n = 14), CIN 3 (n = 28), and squamous cell carcinoma (n = 24) were immunohistochemically stained with LAMR antibody and its expression percentage, pattern, and intensity in these tissues were assessed. Compared to the other groups, the nonstaining with LAMR was highest in low grade squamous intraepithelial lesion (LSIL) (p < 0.0001). LAMR expression, which was positive in less than 50% of cells with weak staining, increased significantly between normal cervical epithelium and high-grade squamous intraepithelial lesion (HSIL) or invasive carcinoma, as well as between LSIL and HSIL (p < 0.0001). Between LSIL and invasive carcinoma, a significant increment was also observed for weak staining in less than 50% of cells (p < 0.001). LAMR expression, which was positive in more than 50% of cells with strong staining, was significantly higher in normal cervical tissue compared to the other groups (p < 0.0001). Disease progression related gradual increment of LAMR expression from normal cervical epithelium or LSIL towards HSIL or cervical cancer reveals that LAMR may play an important role in the transition from premalignant to malignant state in cervical lesions.


Subject(s)
Carcinoma, Squamous Cell , Receptors, Laminin , Uterine Cervical Dysplasia , Uterine Cervical Neoplasms , Humans , Female , Uterine Cervical Neoplasms/metabolism , Uterine Cervical Neoplasms/pathology , Carcinoma, Squamous Cell/metabolism , Carcinoma, Squamous Cell/pathology , Receptors, Laminin/metabolism , Uterine Cervical Dysplasia/metabolism , Uterine Cervical Dysplasia/pathology , Immunohistochemistry , Precancerous Conditions/metabolism , Precancerous Conditions/pathology , Cervix Uteri/pathology , Cervix Uteri/metabolism , Adult , Middle Aged
13.
Nature ; 629(8012): 679-687, 2024 May.
Article in English | MEDLINE | ID: mdl-38693266

ABSTRACT

Pancreatic intraepithelial neoplasias (PanINs) are the most common precursors of pancreatic cancer, but their small size and inaccessibility in humans make them challenging to study1. Critically, the number, dimensions and connectivity of human PanINs remain largely unknown, precluding important insights into early cancer development. Here, we provide a microanatomical survey of human PanINs by analysing 46 large samples of grossly normal human pancreas with a machine-learning pipeline for quantitative 3D histological reconstruction at single-cell resolution. To elucidate genetic relationships between and within PanINs, we developed a workflow in which 3D modelling guides multi-region microdissection and targeted and whole-exome sequencing. From these samples, we calculated a mean burden of 13 PanINs per cm3 and extrapolated that the normal intact adult pancreas harbours hundreds of PanINs, almost all with oncogenic KRAS hotspot mutations. We found that most PanINs originate as independent clones with distinct somatic mutation profiles. Some spatially continuous PanINs were found to contain multiple KRAS mutations; computational and in situ analyses demonstrated that different KRAS mutations localize to distinct cell subpopulations within these neoplasms, indicating their polyclonal origins. The extensive multifocality and genetic heterogeneity of PanINs raises important questions about mechanisms that drive precancer initiation and confer differential progression risk in the human pancreas. This detailed 3D genomic mapping of molecular alterations in human PanINs provides an empirical foundation for early detection and rational interception of pancreatic cancer.


Subject(s)
Exome Sequencing , Mutation , Pancreatic Neoplasms , Precancerous Conditions , Proto-Oncogene Proteins p21(ras) , Humans , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/pathology , Proto-Oncogene Proteins p21(ras)/genetics , Precancerous Conditions/genetics , Precancerous Conditions/pathology , Carcinoma in Situ/genetics , Carcinoma in Situ/pathology , Pancreas/cytology , Female , Genomics , Single-Cell Analysis , Male , Machine Learning , Clone Cells/metabolism , Clone Cells/cytology , Genetic Heterogeneity , Imaging, Three-Dimensional , Adult , Workflow
14.
Methods Cell Biol ; 186: 25-49, 2024.
Article in English | MEDLINE | ID: mdl-38705603

ABSTRACT

One of the earliest applications of flow cytometry was the measurement of DNA content in cells. This method is based on the ability to stain DNA in a stoichiometric manner (i.e., the amount of stain is directly proportional to the amount of DNA within the cell). For more than 40years, a number of studies have consistently demonstrated the utility of DNA flow cytometry as a potential diagnostic and/or prognostic tool in patients with most epithelial tumors, including pre-invasive lesions (such as dysplasia) in the gastrointestinal tract. However, its availability as a clinical test has been limited to few medical centers due to the requirement for fresh tissue in earlier studies and perceived technical demands. However, more recent studies have successfully utilized formalin-fixed paraffin-embedded (FFPE) tissue to generate high-quality DNA content histograms, demonstrating the feasibility of this methodology. This review summarizes step-by-step methods on how to perform DNA flow cytometry using FFPE tissue and analyze DNA content histograms based on the published consensus guidelines in order to assist in the diagnosis and/or risk stratification of many different epithelial tumors, with particular emphasis on dysplasia associated with Barrett's esophagus and inflammatory bowel disease.


Subject(s)
Flow Cytometry , Gastrointestinal Neoplasms , Genomic Instability , Humans , Flow Cytometry/methods , Gastrointestinal Neoplasms/genetics , Gastrointestinal Neoplasms/diagnosis , Gastrointestinal Neoplasms/pathology , Genomic Instability/genetics , Precancerous Conditions/genetics , Precancerous Conditions/diagnosis , Precancerous Conditions/pathology , Tissue Fixation/methods , Paraffin Embedding/methods , DNA/genetics , DNA/analysis , Gastrointestinal Tract/pathology , Gastrointestinal Tract/metabolism , Barrett Esophagus/genetics , Barrett Esophagus/pathology , Barrett Esophagus/diagnosis
15.
J Cancer Res Clin Oncol ; 150(5): 265, 2024 May 20.
Article in English | MEDLINE | ID: mdl-38769201

ABSTRACT

BACKGROUND: Incidental colorectal fluorodeoxyglucose (FDG) uptake, observed during positron emission tomography/computed tomography (PET/CT) scans, attracts particular attention due to its potential to represent both benign and pre-malignant/malignant lesions. Early detection and excision of these lesions are crucial for preventing cancer development and reducing mortality. This research aims to evaluate the correlation between incidental colorectal FDG uptake on PET/CT with colonoscopic and histopathological results. METHODS: Retrospective analysis was performed on data from all patients who underwent PET/CT between December 2019 and December 2023 in our hospital. The study included 79 patients with incidental colonic FDG uptake who underwent endoscopy. Patient characteristics, imaging parameters, and the corresponding colonoscopy and histopathological results were studied. A comparative analysis was performed among the findings from each of these modalities. The optimal cut-off value of SUVmax for 18F-FDG PET/CT diagnosis of premalignant and malignant lesions was determined by receiver operating characteristic (ROC) curves. The area under the curve (AUC) of SUVmax and the combined parameters of SUVmax and colonic wall thickening (CWT) were analyzed. RESULTS: Among the 79 patients with incidental colorectal FDG uptake, histopathology revealed malignancy in 22 (27.9%) patients and premalignant polyps in 22 (27.9%) patients. Compared to patients with benign lesions, patients with premalignant and malignant lesions were more likely to undergo a PET/CT scan for primary evaluation (p = 0.013), and more likely to have focal GIT uptake (p = 0.001) and CWT (p = 0.001). A ROC curve analysis was made and assesed a cut-off value of 7.66 SUVmax (sensitivity: 64.9% and specificity: 82.4%) to distinguish premalignant and malignant lesions from benign lesions. The AUCs of the SUVmax and the combined parameters of SUVmax and CWT were 0.758 and 0.832 respectively. CONCLUSION: For patients undergo PET/CT for primary evaluation, imaging features of colorectal focal FDG uptake and CWT were more closely associated with premalignant and malignant lesions. The SUVmax helps determine benign and premalignant/malignant lesions of the colorectum. Moreover, the combination of SUVmax and CWT parameters have higher accuracy in estimating premalignant and malignant lesions than SUVmax.


Subject(s)
Colonoscopy , Fluorodeoxyglucose F18 , Incidental Findings , Positron Emission Tomography Computed Tomography , Radiopharmaceuticals , Humans , Positron Emission Tomography Computed Tomography/methods , Male , Female , Middle Aged , Retrospective Studies , Aged , Colonic Neoplasms/diagnostic imaging , Colonic Neoplasms/pathology , Colonic Neoplasms/diagnosis , Adult , Precancerous Conditions/diagnostic imaging , Precancerous Conditions/pathology , Precancerous Conditions/diagnosis , Colorectal Neoplasms/pathology , Colorectal Neoplasms/diagnostic imaging , Colorectal Neoplasms/diagnosis , Aged, 80 and over , Clinical Relevance
16.
Nat Commun ; 15(1): 4211, 2024 May 17.
Article in English | MEDLINE | ID: mdl-38760334

ABSTRACT

The cumulative number of stem cell divisions in a tissue, known as mitotic age, is thought to be a major determinant of cancer-risk. Somatic mutational and DNA methylation (DNAm) clocks are promising tools to molecularly track mitotic age, yet their relationship is underexplored and their potential for cancer risk prediction in normal tissues remains to be demonstrated. Here we build and validate an improved pan-tissue DNAm counter of total mitotic age called stemTOC. We demonstrate that stemTOC's mitotic age proxy increases with the tumor cell-of-origin fraction in each of 15 cancer-types, in precancerous lesions, and in normal tissues exposed to major cancer risk factors. Extensive benchmarking against 6 other mitotic counters shows that stemTOC compares favorably, specially in the preinvasive and normal-tissue contexts. By cross-correlating stemTOC to two clock-like somatic mutational signatures, we confirm the mitotic-like nature of only one of these. Our data points towards DNAm as a promising molecular substrate for detecting mitotic-age increases in normal tissues and precancerous lesions, and hence for developing cancer-risk prediction strategies.


Subject(s)
DNA Methylation , Epigenesis, Genetic , Mitosis , Mutation , Neoplasms , Precancerous Conditions , Humans , Mitosis/genetics , Precancerous Conditions/genetics , Precancerous Conditions/pathology , Neoplasms/genetics , Neoplasms/pathology , Stem Cells/metabolism
17.
Sci Rep ; 14(1): 12076, 2024 May 27.
Article in English | MEDLINE | ID: mdl-38802525

ABSTRACT

Cervical cancer (CC) ranks as the fourth most common form of cancer affecting women, manifesting in the cervix. CC is caused by the Human papillomavirus (HPV) infection and is eradicated by vaccinating women from an early age. However, limited medical facilities present a significant challenge in mid- or low-income countries. It can improve the survivability rate and be successfully treated if the CC is detected at earlier stages. Current technological improvements allow for cost-effective, more sensitive, and rapid screening and treatment measures for CC. DL techniques are widely adopted for the automated detection of CC. DL techniques and architectures are used to detect CC and provide higher detection performance. This study offers the design of Enhanced Cervical Precancerous Lesions Detection and Classification using the Archimedes Optimization Algorithm with Transfer Learning (CPLDC-AOATL) algorithm. The CPLDC-AOATL algorithm aims to diagnose cervical cancer using medical images. At the preliminary stage, the CPLDC-AOATL technique involves a bilateral filtering (BF) technique to eliminate the noise in the input images. Besides, the CPLDC-AOATL technique applies the Inception-ResNetv2 model for the feature extraction process, and the use of AOA chose the hyperparameters. The CPLDC-AOATL technique involves a bidirectional long short-term memory (BiLSTM) model for the cancer detection process. The experimental outcome of the CPLDC-AOATL technique emphasized the superior accuracy outcome of 99.53% over other existing approaches under a benchmark dataset.


Subject(s)
Algorithms , Precancerous Conditions , Uterine Cervical Neoplasms , Humans , Female , Uterine Cervical Neoplasms/diagnosis , Uterine Cervical Neoplasms/virology , Precancerous Conditions/diagnosis , Early Detection of Cancer/methods , Machine Learning
19.
BMC Womens Health ; 24(1): 266, 2024 Apr 27.
Article in English | MEDLINE | ID: mdl-38678278

ABSTRACT

BACKGROUND: Uganda has approximately 1.2 million people aged 15-64 years living with human immunodeficiency virus (HIV). Previous studies have shown a higher prevalence of premalignant cervical lesions among HIV-positive women than among HIV-negative women. Additionally, HIV-infected women are more likely to have human papilloma virus (HPV) infection progress to cancer than women not infected with HIV. We determined the prevalence of premalignant cervical lesions and their association with HIV infection among women attending a cervical cancer screening clinic at Mbarara Regional Referral Hospital (MRRH) in southwestern Uganda. METHODS: We conducted a comparative cross-sectional study of 210 women aged 22-65 years living with HIV and 210 women not living with HIV who were systematically enrolled from March 2022 to May 2022. Participants were subjected to a structured interviewer-administered questionnaire to obtain their demographic and clinical data. Additionally, Papanicolaou smears were obtained for microscopy to observe premalignant cervical lesions. Multivariate logistic regression was performed to determine the association between HIV status and premalignant cervical lesions. RESULTS: The overall prevalence of premalignant cervical lesions in the study population was 17% (n = 72; 95% C.I: 14.1-21.4), with 23% (n = 47; 95% C.I: 17.8-29.5) in women living with HIV and 12% (n = 25; 95% C.I: 8.2-17.1) in women not living with HIV (p < 0.003). The most common premalignant cervical lesions identified were low-grade squamous intraepithelial lesions (LSIL) in both women living with HIV (74.5%; n = 35) and women not living with HIV (80%; n = 20). HIV infection was significantly associated with premalignant lesions (aOR: 2.37, 95% CI: 1.27-4.42; p = 0.007). CONCLUSION: Premalignant cervical lesions, particularly LSILs, were more common in HIV-positive women than in HIV-negative women, highlighting the need to strengthen the integration of cervical cancer prevention strategies into HIV care programs.


Subject(s)
Early Detection of Cancer , HIV Infections , Precancerous Conditions , Uterine Cervical Neoplasms , Humans , Female , Adult , Cross-Sectional Studies , Uganda/epidemiology , Uterine Cervical Neoplasms/epidemiology , Uterine Cervical Neoplasms/diagnosis , Middle Aged , Young Adult , Early Detection of Cancer/methods , Early Detection of Cancer/statistics & numerical data , HIV Infections/complications , HIV Infections/epidemiology , Prevalence , Precancerous Conditions/epidemiology , Aged , Papanicolaou Test/statistics & numerical data , Tertiary Care Centers/statistics & numerical data , HIV Seropositivity/epidemiology , HIV Seropositivity/complications , Uterine Cervical Dysplasia/epidemiology , Uterine Cervical Dysplasia/diagnosis , Papillomavirus Infections/epidemiology , Papillomavirus Infections/complications , Vaginal Smears/statistics & numerical data
20.
Pan Afr Med J ; 47: 50, 2024.
Article in English | MEDLINE | ID: mdl-38681110

ABSTRACT

Introduction: visual inspection is a low-cost screening strategy that can be used to prevent cervical cancer in women. These techniques can improve screening health outcomes for internally displaced women (IDW) who have poor sexual and reproductive health and rights' behaviors and outcomes. This study aimed to determine the prevalence of precancerous lesions and other clinical features using a visual inspection with acetic acid (VIA) technique during a cervical cancer screening campaign in two internally displaced people (IDP) camps in Benue State, Nigeria. Methods: this was a cross-sectional study of 166 IDW who voluntarily participated in the study during a VIA cervical cancer screening campaign in two IDP camps in Benue State, Nigeria the screening was done by a group of qualified and trained healthcare workers and data was collected using a structured, pretested questionnaire. Results: a total of 99(60%) of the women had a first sexual experience at 16 years, while 78(47%) had more than 5 full-term pregnancies. Although only 72(43.4%) of the women acknowledged having more than one sexual partner, over 70% of the women stated that their sexual partner had another sexual partner. The prevalence of precancerous lesions among women was 10.8%. Smoking(p=0.003), age at menarche (p≤ 0.001) and sexual behaviors (p=0.009, p=0.004) were factors that had a statistically significant relationship with the presence of a precancerous lesion among the IDW. The study also highlights the high rate (95%) of cervicitis among the women and the relatively high rate (5.4%) of leukoplakia. Conclusion: the majority of IDW had sociodemographic and lifestyle characteristics that predisposed them to developing cervical cancer More targeted interventions aimed at improving the sociodemographic and lifestyle characteristics of IDW are recommended. In addition, there is a need to create awareness about cervical cancer among IDW and make screening available in camp facilities for early detection and management.


Subject(s)
Early Detection of Cancer , Precancerous Conditions , Uterine Cervical Neoplasms , Humans , Female , Nigeria/epidemiology , Cross-Sectional Studies , Uterine Cervical Neoplasms/epidemiology , Uterine Cervical Neoplasms/diagnosis , Prevalence , Adult , Precancerous Conditions/epidemiology , Precancerous Conditions/pathology , Middle Aged , Young Adult , Surveys and Questionnaires , Mass Screening/methods , Refugees/statistics & numerical data , Sexual Behavior/statistics & numerical data , Acetic Acid , Sexual Partners , Adolescent , Smoking/epidemiology
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