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Actinic keratosis (AK) is a common precancerous skin condition predominantly affecting older males with fair skin and significant UV exposure. The clinical significance of AK is related to its potential for malignant transformation and progression to squamous cell carcinoma (SCC). Accurate diagnosis of AK is essential for adequate treatment, evaluation of therapeutic efficacy, and mitigating the risk of developing SCC. However, clinician variability due to the subjective nature of current diagnostic tools presents significant challenges to achieving consistent and reliable AK diagnoses. Thus, there is no universally accepted standard for measuring AK.This review evaluates current methods for evaluating and diagnosing AK, focusing on clinician variability through inter- and intraobserver agreement. Eight peer-reviewed studies investigating the reliability of various approaches for AK evaluation show substantial variability in interobserver or intraobserver agreement, with most methods demonstrating only slight to moderate reliability. Some suggest that consensus discussions and simplified rating scales can modestly improve diagnostic reliability. However, remaining variability and the lack of a universally accepted standard for measuring AK underscore the need for more robust and standardized diagnostic and evaluation methods.The review emphasizes the need for improved diagnostic tools and standardized methods to enhance the accuracy and reliability of AK assessments. It also proposes applying a novel examination approach using 1,3-dihydroxyacetone (DHA) staining which may improve the visualization and identification of AK lesions. Advancements in these areas have significant potential, promising better clinical practices and patient outcomes in AK management.

The article discusses the establishment of the American College of Radiology (ACR) Pediatric LI-RADS Working Group to address the lack of a standardized system for pediatric liver tumors. It highlights the differences between adult and pediatric liver tumors, emphasizing the increasing incidence of hepatoblastoma (HB) and the unique characteristics of pediatric hepatocellular carcinoma (HCC). The group aims to optimize pediatric liver imaging through advocacy, education, and research, providing consensus imaging recommendations and guidelines for evaluating pediatric liver lesions. The research conducted by the group indicates that while the LI-RADS criteria may not fully apply to pediatric cases, they can still aid in differentiating malignant and benign lesions and guiding biopsy decisions. The importance of surveillance imaging for children with predispositions to liver tumors is also emphasized for early detection and better outcomes. [Extracted from the article]

Colorectal intraepithelial neoplasia is a precancerous lesion of colorectal cancer, which is mainly diagnosed using pathological images. According to the characteristics of lesions, precancerous lesions can be classified into four different grades, i.e., background, normal, low and high level. However, due to the continuity of lesion development, tissue in different stages has high similarity. Recently, visual transformers have achieved impressive results in different visual tasks, due to their capacity of capturing long-range dependencies. However, due to computational cost, transformer cannot well extract detailed feature, which is important for lesion grading. To accurately segment pathological tissues with high similarity, in this work, we embed the multi-head MLP mixer module in the transformer network to extract cell and edge information. Furthermore, we propose a hierarchical MLP decoder to facilitate multi-scale feature fusion. The proposed transformer, namely MLPFormer, achieves remarkable results against competitive baselines on the Histo-CRC Biopsy dataset. The experimental results demonstrate that MLPFormer significantly outperforms the competitive baselines, i.e., a 3% dice improvement is achieved over the SegFormer series. [ABSTRACT FROM AUTHOR]

Background: Cervical cancer (CC) is preventable, yet remains a significant public health threat, particularly in Sub-Saharan Africa. Despite considerable awareness, screening rates for CC in Kenya are low and loss to follow-up following treatment for premalignant cervical lesions remains high. This study investigates the efficacy of the Cancer Tracking System (CATSystem), a web-based intervention, to improve CC screening and treatment retention. Methods: A matched, cluster randomized controlled trial will be conducted in Kenyan government hospitals (n = 10) with five intervention and five standard-of-care (SOC) sites. The primary outcome is the proportion of women with a positive screen who receive appropriate treatment (onsite or referral). Secondary outcomes include CC screening uptake among all women and timeliness of treatment initiation. We will utilize mixed methods to assess intervention feasibility, acceptability, and cost-effectiveness. Discussion: The CATSystem has the potential to improve CC care in Kenya by leveraging existing technology to address known barriers in the screening and treatment cascade. This study will provide valuable evidence for potential scale-up of the intervention. [ABSTRACT FROM AUTHOR]

Background: Clinical practice guidelines (CPGs) are intended to offer appropriate recommendations for clinical practice based on the available evidence while acknowledging existing gaps and uncertainties. The quality of CPGs for gastric precancerous lesions (GPL), distribution of evidence quality, and strength of recommendations are unknown. Objective: Systematically evaluate the quality of CPGs for GPL and identify areas for improvement in the development process. Methods: PubMed, Embase, Cochrane Library, Cumulative Index to Nursing and Allied Health Literature, and six online CPG repositories were systematically searched for CPGs related to GPL. Three researchers independently assessed the methodological quality of the included CPGs by using the AGREE II tool. The reporting and recommendation quality of the CPGs were evaluated using the RIGHT and AGREE-REX tools through consensus. Evidence-based CPGs were analyzed using the Grading of Recommendation Assessment, Development, and Evaluation system to determine the distribution of quality of evidence and strength of recommendations. Results: A total of 4046 records were identified; nine CPGs met the eligibility criteria for this study. The mean overall score for the methodological quality of the CPGs was 46.22%. Among the six domains, the mean score for clarity of presentation was the highest (71.67%), while the mean score for applicability was the lowest (24.56%). Among the nine CPGs, only one was considered high quality. Regarding reporting quality, domains 1, 3, and 4 had mean reporting rates equal to or higher than 60%. The mean overall score for the recommendation quality was 19.11%. In total, 235 recommendations were identified through the screening process, of which 64.4% were classified as strong. However, only 17.5% of the strong recommendations were supported by high-quality evidence. Conclusion: The overall quality of CPGs for GPL was poor, with uneven quality across domains. In addition, the consistency between the strength of recommendations and the quality of evidence was poor. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is the 2nd most fatal cancer in the United States, but when detected early it is highly curable. Stool-derived extracellular vesicles (EVs) are a novel biomarker source that could augment the sensitivity for detection of CRC precursors. However, standardization of isolation methods for stool-derived EVs remains underexplored. We previously reported that size-exclusion chromatography (SEC) followed by ultrafiltration (UF-100kDa) was suitable for human stool supernatant EV isolation. In this study, we first assess alternative EV concentration methods (ultrafiltration [UF]; 10 kDa, 30 kDa, 50 kDa, 100 kDa and speed vacuum [SV]). Second, we investigate the host/bacterial EV proteomes by mass spectrometry. We report no difference in recovery, RNA and soluble protein contamination among concentration methods. Proteomic analysis reveals a diverse bacterial proteome, while human-derived proteins are more abundant. Specifically, pancreatic enzymes are among the most abundant proteins, further exploration revealed that zymogen granules are likely co-isolated in stool EV preparations. To enable discovery of EV-based molecular signatures of CRC precursors with high sensitivity, immunocapture strategies will likely be needed. Notably, we identified 10 surface proteins that may serve as candidates for the purification of colon-derived EVs. This work serves as framework for the future discovery and validation of EV-based biomarkers for CRC. This work uncovers the complex proteomic landscape of stool-derived extracellular vesicles (EVs). These findings serve as the framework for future stool EV biomarker discovery in gastrointestinal tract malignancies. [ABSTRACT FROM AUTHOR]

Molecular testing for human papillomaviruses (HPV) is gradually replacing cytology in cervical cancer screening. In this longitudinal population‐based cohort study, 4140 women 20 to 64 years old attending organized screening were tested at baseline by five different screening methods and followed for 9 years. To assess long‐term safety, the cumulative risks of CIN2+/CIN3+ were estimated after a negative baseline result obtained by conventional cytology and four clinically validated HPV assays: Hybrid Capture 2 (hc2), RealTime High Risk HPV assay (RealTime), cobas 4800 HPV Test (cobas_4800), and Alinity m HR HPV (Alinity). HPV‐negative women at baseline had a substantially lower risk for CIN2+ compared to those with normal baseline cytology: 0.84% (95% CI, 0.46–1.22), 0.90% (95% CI, 0.51–1.29), 0.78% (95% CI, 0.42–1.15), and 0.75% (95% CI, 0.39–1.11) for hc2, RealTime, cobas_4800, and Alinity, respectively, compared to 2.46% (95% CI, 1.88–3.03) for cytology. No differences were observed between HPV assays in longitudinal sensitivity (range: 86.21%–90.36%) and negative predictive values (range: 99.54%–99.70%) for CIN2+ in women ≥30 years, but were significantly different from cytology (p <.05). The 9‐year cumulative risk of CIN2+ differed significantly between HPV genotypes, reaching 32.1% (95% CI, 14.5–46.1) for HPV16, 24.9% (95% CI, 4.7–40.8) for HPV18/45, 27.2% (95% CI, 14.6–37.8) for HPV31/33/35/52/58, and 8.1% (95% CI, 0.0–16.7) for HPV39/51/56/59. Four clinically validated HPV assays showed comparable safety and better assurance against precancerous lesions than cytology, but some important differences were identified in the performance characteristics of HPV assays impacting the referral rate. Information about the HPV genotype is valuable for guiding further clinical action in HPV‐based screening programs. [ABSTRACT FROM AUTHOR]

Barrett's esophagus (BE) represents a pre-cancerous condition that is characterized by the metaplastic conversion of the squamous esophageal epithelium to a columnar intestinal-like phenotype. BE is the consequence of chronic reflux disease and has a potential progression burden to esophageal adenocarcinoma (EAC). The pathogenesis of BE and EAC has been extensively studied but not completely understood, and it is based on two main hypotheses: "transdifferentiation" and "transcommitment". Omics technologies, thanks to the potentiality of managing huge amounts of genetic and epigenetic data, sequencing the whole genome, have revolutionized the understanding of BE carcinogenesis, paving the way for biomarker development helpful in early diagnosis and risk progression assessment. Genomics and transcriptomics studies, implemented with the most advanced bioinformatics technologies, have brought to light many new risk loci and genomic alterations connected to BE and its progression to EAC, further exploring the complex pathogenesis of the disease. Early mutations of the TP53 gene, together with late aberrations of other oncosuppressor genes (SMAD4 or CKND2A), represent a genetic driving force behind BE. Genomic instability, nonetheless, is the central core of the disease. The implementation of transcriptomic and proteomic analysis, even at the single-cell level, has widened the horizons, complementing the genomic alterations with their transcriptional and translational bond. Increasing interest has been gathered around small circulating genetic traces (circulating-free DNA and micro-RNAs) with a potential role as blood biomarkers. Epigenetic alterations (such as hyper or hypo-methylation) play a meaningful role in esophageal carcinogenesis as well as the study of the tumor micro-environment, which has led to the development of novel immunological therapeutic options. Finally, the esophageal microbiome could be the protagonist to be investigated, deepening our understanding of the subtle association between the host microbiota and tumor development. [ABSTRACT FROM AUTHOR]

Background: This study aims to compare the effectiveness and safety of traditional endoscopic submucosal dissection (ESD), endoscopic submucosal tunneling dissection (ESTD), and endoscopic submucosal dissection with C-shaped incision (ESD-C) in the treatment of superficial esophageal cancer and precancerous lesions, providing reference and guidance for the treatment of esophageal cancer. Methods: A retrospective analysis was conducted on the clinical data of patients who underwent ESD (n = 96), ESTD (n = 103), and ESD-C (n = 98) for superficial esophageal cancer or precancerous lesions between January 2017 and December 2022. Through comparative analysis, the effectiveness and safety of the three surgical methods were evaluated, and the risk factors for postoperative esophageal stricture were explored. Results: In terms of total operative time and dissection time, the ESD group > ESTD group > ESD-C group; in terms of dissection speed, the ESD group < ESTD group < ESD-C group; in terms of dissection area, the ESD group < ESTD group and ESD-C group; and in terms of wound treatment time, the ESD group > ESTD group and ESD-C group. In terms of surgical outcomes, the en bloc resection rate was 100% in all three groups, with complete resection rates of 86.84%, 90.79%, and 88.16% in the ESD, ESTD, and ESD-C groups, respectively. The risk factors for postoperative esophageal stricture included dissection area, circumferential proportion of the lesion, and injury to the muscularis propria. Conclusion: Among the three surgical approaches, ESD-C demonstrated superior performance in operative time, resection speed, and procedural efficiency. Increased circumferential involvement of the lesion, larger resection area, and greater injury to the muscularis propria were associated with a heightened risk of postoperative esophageal stricture. [ABSTRACT FROM AUTHOR]

Cervical cancer belongs to the most dangerous types of cancers posing considerable threat to women's survival. It is most often diagnosed in the advanced stages as precancerous lesions are often symptom-free and difficult to identify. Microwave imaging, especially in terahertz (THz) range, is a convenient and noninvasive cancer detection tool. It enables characterization of biological tissues and discrimination between healthy and malignant ones. This study presents a novel triple-band biosensor based on metamaterials (MTMs). By leveraging unique properties of MTMs, the proposed biosensor operates as a perfect absorber. It exploits resonant modes in the THz spectrum to achieve remarkable sensitivity. Meticulous selection of the sensor geometry and dimensions enables efficient miniaturization. Meanwhile, utilization of frequency-domain data to detect refractive index changes improves resolution of cancerous tissue identification. Extensive numerical investigations corroborate its ability to carry out reliable early-stage cervical cancer diagnosis. This includes identification of the spatial extent of the malignant tissue. Excellent electrical properties of the sensor are accompanied by its compact size, which is highly desirable for non-invasive and portable applications. [ABSTRACT FROM AUTHOR]

As in any other field, medicine is advancing and striving to adapt to increasingly complex demands, aiming to find rapid solutions in establishing certain diagnoses that can save or significantly improve the patient's quality of life. The integration of Al systems in the medical field is vital and requires openness, as well as a continuous desire for learning and improvement. Although the use of artificial intelligence in the medical field in Romania has not yet reached widespread development, there are still some Al software and applications that prove their effectiveness and ease the work of medical specialists. Oral cancer is one of the most common forms of malignant or premalignant lesions globally, with a high prevalence. Although developed countries are less affected compared to developing ones, they are also seeing an increasing incidence of cancers in the oro-maxillofacial region. The etiology of oral cancer is complex, influenced by both genetic and epigenetic factors. Currently, research is increasingly focused on epigenetic factors, including smoking, chronic alcoholism, diet. and improper use of mouthwash. These behaviours are associated with significant risks for the development of oral cancer, highlighting the importance of awareness and prevention within the global population. In Romania, factors such as low dental visit frequency, poor infrastructure, and lack of education contribute to disease prevalence. According to GLOBOCAN data, oral cancer in Romania ranks second in incidence, after leukemia, with a rate of 5.6 per 100,000 individuals. The purpose of our study is to highlight the importance of histopathological examination in establishing a definitive diagnosis, as well as the significance of Al software used in storing and processing the data obtained in the laboratory. [ABSTRACT FROM AUTHOR]

Background: This study explores the efficacy of combining recombinant human interferon a-2b with the cervical loop electrosurgical excision procedure (LEEP) in the treatment of cervical precancerous lesions. Methods: Clinical data from 100 patients treated for cervical precancerous lesions at our hospital from January 2021 to January 2023 were retrospectively analyzed. Patients were divided into two groups based on treatment method: an experimental group (50 cases) and a control group (50 cases). The control group received LEEP using a high-frequency electric knife, while the experimental group was treated with LEEP combined with recombinant human interferon a-2b gel. The differences in efficacy between the two groups were compared. Results: The experimental group demonstrated a significantly higher overall effective rate compared to the control group (p < 0.05). There was no significant difference in the incidence of surgical complications between the two groups (p > 0.05). At 6 months and 1 year after surgery, the experimental group exhibited a lower recurrence rate and a higher clearance rate of high-risk human papillomavirus (HR-HPV) compared to the control group (p < 0.05). Three months after treatment, the scores for environment, social relationships, physiology and psychology in the experimental group were significantly higher than those in the control group (p < 0.001). Conclusions: Combining LEEP with recombinant human interferon a-2b in patients with cervical precancerous lesions effectively eliminates HPV, improves quality of life, reduces complications and recurrence and is safe for medication. [ABSTRACT FROM AUTHOR]

Purpose: In mucinous ovarian tumors, preoperative prediction of histological subgroup is important for treatment approach. Therefore, we aimed to determine salient magnetic resonance imaging (MRI) findings and estimate optimal cut off values for quantitative features in differential diagnosis of benign, borderline and malignant mucinous ovarian tumors. Methods: Between January 2011 and December 2021, preoperative MRI scans of 50 patients with mucinous ovarian tumors (n = 54) were evaluated retrospectively. MRI findings [size, signal intensity, contrast pattern, features of loculation, wall, septa and mural nodule (MN), diffusion restriction] were investigated. There were benign, borderline, and malignant groups based on histopathological results. The relationship between radiological and histopathological results was analyzed by performing Kruskal Wallis test, Pearson's chi-squared test, receiver operating characteristic analysis. Results: In our study, there were 54 mucinous ovarian tumors in 50 patients. Of 54, 33 were benign, 13 borderline and eight malignant tumors. In comparison of three groups, tumor size, number of loculation, number and frequency of MN were higher and apparent diffusion coefficient (ADC) value were lower in malignant group (p < 0.05). Septa thickness was lower with optimal cut off value of 2.45 mm in benign group compared to borderline and malignant groups [sensitivity: 79%, specificity: 75%, AUC (Area under the curve): 0.861] (p < 0.05). T2-weighted (T2-w) signal intensity ratio (SIR) of MN was higher in borderline compared to malignant group, with a cut-off value of 3.9 (sensitivity: 85%, specificity: 83%, AUC: 0.943) (p < 0.05). Ascites was also significant in malignant group (p < 0.05). Conclusion: T2-w SIR of MN with a cut off value of 3.9 is beneficial for differential diagnosis. By awareness of some salient MRI findings (size, septa thickness, number of loculation, number and T2-w SIR of MN, ADC value and ascites), preoperative prediction of histological subgroup of mucinous tumors for appropriate treatment planning is possible. [ABSTRACT FROM AUTHOR]

Background The role of endoscopic mucosal resection (EMR) for laterally spreading lesions (LSLs) in inflammatory bowel disease (IBD) remains controversial despite its effectiveness in the general population. We aimed to characterize outcomes of EMR for IBD-associated LSLs compared with controls without IBD. Methods We performed a retrospective observational cohort study of patients with IBD who underwent EMR and endoscopic follow-up for LSLs, compared with a control group without IBD. The primary outcome was histologic recurrence. Secondary outcomes included en bloc resection and adverse events. Factors associated with recurrence were identified using multivariate mixed effects logistic regression. Results 210 premalignant lesions in 155 patients were included. By histology, 91.0% were adenoma/low grade dysplasia or sessile serrated lesions. Median (IQR) lesion size was 25 (12–30) mm in the IBD group and 20 (12–30) mm in the control group. Recurrence was detected in 30.4% of IBD-associated lesions (7/23) compared with 20.9% of controls (39/187; odds ratio [OR] 2.51, 95%CI 0.59–10.71). En bloc resection was less common in the IBD group (2/23 [8.7%], 95%CI 1.1–28.0) versus controls (106/187 [56.7%], 95%CI 50.4–65.2). After adjusting for lesion size and histology, recurrence appeared more common in patients with IBD compared with controls (OR 3.08, 95%CI 1.04–9.13). Conclusions Recurrence of LSLs after EMR appeared to be more frequent in patients with IBD. Given the added complexity, EMR in patients with IBD should be performed in expert centers with close endoscopic surveillance. [ABSTRACT FROM AUTHOR]

Pancreatic cancer has dismal prognosis with a 5-year survival of 12 %. Cystic lesions have been identified as premalignant lesions. The challenge is to identify lesions with high risk of malignant progression, to offer patients prophylactic curative pancreatic surgery. Previous studies have identified mucin biomarker panels (MUCPs) as potential discriminators of pre- and malignant pancreatic cystic lesions. The present study assessed whether MUCPs contribute to more accurate identification of patients with high-risk pancreatic lesions and improve selection for surgery. This retrospective crossover study included 88 patients referred to endoscopic ultrasound because of unclear pancreatic cystic lesions. Clinical management and surgical decision-making with and without MUCP values were assessed by two expert teams with access to patient medical history, radiology, fine-needle aspirates, cytology, and cystic fluid carcinoembryonic antigen. The adjunct of MUCPs improved decision-making in 2 of 21 cases with surgical pathology, identifying one cancer that otherwise would have been missed and sparing one patient from unnecessary surgery. Access to MUCPs in a clinical setting improved correct selection of high-risk pancreatic lesions for surgery in single cases. A higher number of incorrect recommendations for surgery with the adjunct of MUCPs was also noted, which calls for caution. [ABSTRACT FROM AUTHOR]

Introduction: Cervical cancer is a preventable and highly curable disease when detected early and adequately treated, yet it remains the leading cause of cancer-related death in women in Kenya due to low screening coverage and treatment. Implementing World Health Organization screening guidelines for human papillomavirus (HPV) is challenging due to the complex logistics of result return and follow-up requiring multiple clinic visits. Increasing the use of mobile technology can support follow-up care in cervical cancer screening programs. Methods: We developed a prospective clinico-economic model to assess the potential impact of a mobile phone-based application ("app") communicating laboratory results and recommendations to improve follow-up care for cervical cancer screening in Kenya. The model is structured to simulate a three-visit pathway for HPV-based screening used in a clinical trial of the app and based on epidemiological data, clinical guideline-based workflow, and patient-based behavioral pathways. Published literature, expert elicitation, and time-and-motion observations were used to estimate clinical data, care pathways, and visit-related costs. This analysis was conducted from a base-case healthcare system perspective with a scenario from a "limited" societal perspective. Results: In a simulated cohort of women using the app-based intervention compared to conventional care, with 10,000 women in each arm, use of the app is projected to increase healthcare costs by $12.53 per enrolled woman during the trial period and to detect and treat an additional 247 women—229 with precancerous cervical lesions and 18 with cervical cancer. The incremental cost-effectiveness ratio of the app versus conventional care was $174 per case detected and treated. This would be cost-saving given the average lifetime cost per cervical cancer case of $1,000–$3,000. Conclusion: Use of a mobile phone-based app is costlier than conventional screening but by improving visit compliance, it can be a cost-effective and cost-saving strategy to enhance detection and treatment in cervical cancer screening programs. [ABSTRACT FROM AUTHOR]

Objectives: This study investigates the performance of artificial intelligence (AI) technology, namely Cerviray AI®, compared with Cerviray® expert, aiming to compare its sensitivity, specificity, positive predictive value (PPV), and area under the receiver operating characteristic curve (AUC ROC). The Visual Inspection with Acetic Acid (VIA) test is used as the gold standard. Results: The study involved 44 patients from various health centers in West Java Province. Performance of Cerviray AI®, or Cerviray® expert, and lastly VIA tests were compared in their ability to detect pre-cancerous cervical lesions in high-risk women of childbearing age. The current study indicated that Cerviray AI® had a sensitivity of 42.9%, specificity of 100%, PPV of 100%, and ROC AUC values of 71.4%. In comparison, the evaluation of the Cerviray® expert demonstrated a sensitivity of 71.4%, specificity of 97.3%, PPV of 83.3%, and ROC AUC values of 84.4%. In conclusion, the evaluation of Cerviray® expert outperformed Cerviray AI® in ROC AUC values. Trial registration: Clinical Trials.gov Identifier NCT06518070 Retrospectively registered. [ABSTRACT FROM AUTHOR]

Mutations in Sonic Hedgehog (SHH) signaling pathway genes, for example, Suppressor of Fused (SUFU), drive granule neuron precursors (GNP) to form medulloblastomas (MBSHH). However, how different molecular lesions in the Shh pathway drive transformation is frequently unclear, and SUFU mutations in the cerebellum seem distinct. In this study, we show that fibroblast growth factor 5 (FGF5) signaling is integral for many infantile MBSHH cases and that FGF5 expression is uniquely upregulated in infantile MBSHH tumors. Similarly, mice lacking SUFU (Sufu-cKO) ectopically express Fgf5 specifically along the secondary fissure where GNPs harbor preneoplastic lesions and show that FGFR signaling is also ectopically activated in this region. Treatment with an FGFR antagonist rescues the severe GNP hyperplasia and restores cerebellar architecture. Thus, direct inhibition of FGF signaling may be a promising and novel therapeutic candidate for infantile MBSHH. [ABSTRACT FROM AUTHOR]

Background: Persistent infection with high-risk human papillomavirus (HPV) is a significant risk factor for cervical cancer. HPV typing and cytology are conducted in women of appropriate age to assess the risk of cervical lesions and to guide the need for further diagnostic procedures such as colposcopy, cervical biopsy, or treatment. This article explores methods to predict the risks of high-grade precancerous cervical lesions based on high-risk HPV typing. Methods: We conducted a retrospective analysis of HPV typing data from 158,565 women, including 19,707 who underwent ThinPrep cytologic testing (TCT), 7,539 who had colposcopy examinations, and 4,762 who had biopsies. We evaluated the sensitivity, specificity, and risk parameters of high-grade lesions associated with high-risk HPV types. Results: (1) The overall prevalence of HPV infection was 17.89%, with the most prevalent types being HPV52 (4.44%), HPV58 (2.10%), HPV53 (1.96%), HPV81 (1.85%), HPV42 (1.75%), and HPV16 (1.44%). (2) The sensitivity and specificity of detecting high-grade lesions in TCT, colposcopy, and biopsy, based on high-risk HPV typing, demonstrated a strong linear correlation with the infection rate of each type. (3) HPV16 was confirmed to have a higher risk of CIN2 + in biopsies using a self-defined risk parameter. (4) The top five HPV types with the highest PPVs and pathogenicity risks in biopsies were HPV45, HPV16, HPV58, HPV33, and HPV18. Conclusion: In Changsha, China, HPV52, HPV58, and HPV53 were the most prevalent and contributed significantly to high-grade lesions. After adjusting for infection rates, a self-defined risk parameter was proposed as a measure of the intrinsic risks of high-grade lesions associated with high-risk HPV types. Focused monitoring of prevalent high-risk HPV types such as HPV45, HPV16, HPV58, HPV33, and HPV18, which show the highest pathogenicity risks, is recommended in our region. [ABSTRACT FROM AUTHOR]

Photodynamic diagnosis (PDD) and autofluorescence imaging (AFI) are emerging cancer diagnostic technologies that offer significant advantages over traditional white-light endoscopy in detecting precancerous lesions and early-stage cancers; moreover, they hold promising potential in fluorescence-guided surgery (FGS) for tumors. However, their shortcomings have somewhat hindered the clinical application of PDD and AFI. Therefore, it is imperative to enhance the efficacy of PDD and AFI, thereby maximizing their potential for practical clinical use. This article reviews the principles, characteristics, current research status, and advancements of PDD and AFI, focusing on analyzing and discussing the optimization strategies of PDD and AFI in tumor diagnosis and FGS scenarios. Considering the practical and technical feasibility, optimizing PDD and AFI may result in an effective real-time diagnostic tool to guide clinicians in tumor diagnosis and surgical guidance to achieve the best results. [ABSTRACT FROM AUTHOR]

Background: Cervical screening, aimed at detecting precancerous lesions and preventing cancer, is based on cytology and HPV testing. Both methods have limitations, the main ones being the variable diagnostic sensitivity of cytology and the moderate specificity of HPV testing. Various molecular biomarkers are proposed in recent years to improve cervical cancer management, including a number of mRNAs encoded by human genes involved in carcinogenesis. Many scientific papers have shown that the expression patterns of cellular mRNAs reflect the severity of the lesion, and their analysis in cervical smears may outperform HPV testing in terms of diagnostic specificity. However, such analysis has not yet been implemented in broad clinical practice. Our aim was to devise an assay detecting severe cervical lesions (≥HSIL) via analysis of cellular mRNA expression in cytological smears. Methods: Through logistic regression analysis of a reverse-transcription quantitative PCR (RT-qPCR) dataset generated from analysis of six mRNAs in 167 cervical smears with various cytological diagnoses, we generated a family of linear classifiers based on paired mRNA concentration ratios. Each classifier outputs a dimensionless decision function (DF) value that increases with lesion severity. Additionally, in the same specimens, the HPV genotyping, viral load assessment, diagnosis of cervicovaginal microbiome imbalance and profiling of some relevant mRNAs and miRNAs were performed by qPCR-based methods. Results: The best classifiers were obtained with pairs of mRNAs whose expression changes in opposite directions during lesion progression. With this approach based on a five-mRNA combination (CDKN2A , MAL , TMPRSS4 , CRNN , and ECM1), we generated a classifier having ROC AUC 0.935, diagnostic sensitivity 89.7%, and specificity 87.6% for ≥HSIL detection. Based on this classifier, a two-tube RT-qPCR based assay was developed and it confirmed the preliminary characteristics on 120 cervical smears from the test sample. DF values weakly correlated with HPV loads and cervicovaginal microbiome imbalance, thus being independent markers of ≥HSIL risk. Conclusion: Thus, we propose a high-throughput method for detecting ≥HSIL cervical lesions by RT-qPCR analysis of several cellular mRNAs. The method is suitable for the analysis of cervical cytological smears prepared by a routine method. Further clinical validation is necessary to clarify its clinical potential. [ABSTRACT FROM AUTHOR]

Introduction: The current understanding of colorectal carcinogenesis is based on the adenoma-carcinoma sequence, where genetics, intestinal microbiota changes and local immunity shifts seem to play the key roles. Despite the emerging evidence of dysbiotic intestinal state and immune-cell infiltration changes in patients with colorectal adenocarcinoma, early and advanced adenoma as precursors of colorectal cancer, and carcinoma in situ as the following progression, are rather less studied. The newly colon-site adapted AI-based analysis of immune infiltrates is able to predict long-term outcomes of colon carcinoma. Though it could also facilitate the pathologic evaluation of precancerous lesion's potential to progress. Therefore, the purpose of this prospective cohort study (MIMICA-1) is, firstly, to identify the intestinal microbiota and immune infiltration patterns around the normal bowel tissue, early and advanced adenoma, carcinoma in situ, and adenocarcinoma, and secondly, to analyze the immune – microbiome interplay along the steps of conventional colorectal tumorigenesis. Methods and analyses: This study aims to prospectively recruit 40 patients (10 per group) with confirmed colorectal dysplasia undergoing endoscopic polypectomy, endoscopic mucosal resection for colorectal small (≤1cm), and large (>1cm) adenoma or carcinoma in situ, or biopsy and subsequent colon resection for invasive colorectal cancer, and 10 healthy patients undergoing screening colonoscopy. Stool samples will be collected prior to bowel preparation for the analysis of fecal (luminal) microbiota composition. Biopsy specimens will be taken from the terminal ileum, right colon, left colon, and a pathological lesion in the colon (if present) to assess mucosa-associated microbiota composition and intestinal immunity response. DNA will be extracted from all samples and sequenced using the Illumina MiSeq platform. Unifrac and Bray-Curtis methods will be used to assess microbial diversity. The intestinal immune system response will be examined using digital image analysis where primarily immunohistochemistry procedures for CD3, CD8, CD20 and CD68 immune cell markers will be performed. Thereafter, the count, density and distribution of immunocompetent cells in epithelial and stromal tissue compartments will be evaluated using AI-based platform. The interaction between the microbial shifts and intestinal immune system response in adenoma-carcinoma sequence and the healthy patients will be examined. In addition, fecal samples will be explored for gut microbiota's composition, comparing fecal- and tissue-derived bacterial patterns in healthy gut and along the adenoma-carcinoma sequence. Discussion: We hypothesize that changes within the human gut microbiota led to detectable alterations of the local immune response and correlate with the progression from normal mucosa to colorectal adenoma and invasive carcinoma. It is expectable to find more severe gut immune infiltration at dysplasia site, though analyzing invasive colorectal cancer we expect to detect broader mucosa-associated and luminal microbiota changes with subsequent local immune response at near-lesion site and possibly throughout the entire colon. We believe that specific compositional differences detected around premalignant colorectal lesions are critically important for its primary role in initiation and acceleration of colorectal carcinogenesis. Thus, these microbial patterns could potentially supplement fecal immunohistochemical tests for the early non-invasive detection of colorectal adenoma. Moreover, AI-based analysis of immune infiltrates could become additional diagnostic and prognostic tool in precancerous lesions prior to the development of colorectal cancer. Registration: The study is registered at the Australian New Zealand Clinical Trials Registry (ACTRN12624000976583) https://www.anzctr.org.au/. [ABSTRACT FROM AUTHOR]

Pancreatic intraepithelial neoplasia (PanIN) is the most common precursor lesion of pancreatic ductal adenocarcinoma (PDAC), which has poor prognosis with a short median overall survival of 6-12 months and a low 5-year survival rate of approximately 3%. It is crucial to remove PanIN lesions to prevent the development of invasive PDAC, as PDAC spreads rapidly outside the pancreas. This review aims to provide the latest knowledge on PanIN risk, pathology, cellular origin, genetic susceptibility, and diagnosis, while identifying research gaps that require further investigation in this understudied area of precancerous lesions. PanINs are classified into PanIN 1, PanIN 2, and PanIN 3, with PanIN 3 having the highest likelihood of developing into invasive PDAC. Differentiating between PanIN 2 and PanIN 3 is clinically significant. Genetic alterations found in PDAC are also present in PanIN and increase with the grade of PanIN. Imaging methods alone are insufficient for distinguishing PanIN, necessitating the use of genetic and molecular tests for identification. In addition, metabolomics technologies and miRNAs are playing an increasingly important role in the field of cancer diagnosis, offering more possibilities for efficient identification of PanIN. Although detecting and stratifying the risk of PanIN poses challenges, the combined utilization of imaging, genetics, and metabolomics holds promise for improving patient survival in this field. [ABSTRACT FROM AUTHOR]

Endoscopy is vital for detecting and diagnosing gastrointestinal diseases. Systematic examination protocols are key to enhancing detection, particularly for the early identification of premalignant conditions. Publicly available endoscopy image databases are crucial for machine learning research, yet challenges persist, particularly in identifying upper gastrointestinal anatomical landmarks to ensure effective and precise endoscopic procedures. However, many existing datasets have inconsistent labeling and limited accessibility, leading to biased models and reduced generalizability. This paper introduces GastroHUN, an open dataset documenting stomach screening procedures based on a systematic protocol. GastroHUN includes 8,834 images from 387 patients and 4,729 labeled video sequences, all annotated by four experts. The dataset covers 22 anatomical landmarks in the stomach and includes an additional category for unqualified images, making it a valuable resource for AI model development. By providing a robust public dataset and baseline deep learning models for image and sequence classification, GastroHUN serves as a benchmark for future research and aids in the development of more effective algorithms. [ABSTRACT FROM AUTHOR]

Objective: To compare the performance of cytology, HPV16/18 genotyping and PAX1/SOX1 methylation for the triage of high‐risk HPV‐positive cervical samples. Design: Retrospective analyses of archival samples collected from a large‐scale prospective randomised controlled trial. Setting/Sample: HPV‐positive women recruited from the general cervical screening population. Methods: 403 HPV‐positive samples including 113 normal, 173 low‐grade cervical intraepithelial neoplasia (LG‐CIN), 114 HG‐CIN and three cervical cancers. All samples were assessed by liquid‐based cytology, HPV genotyping and PAX1/SOX1 methylation. Main Outcome Measures: AUC (area under the curve), sensitivity and specificity for cytology, HPV16/18 genotyping and PAX1/SOX1 methylation for high‐grade (HG) premalignant cervical lesions. Results: PAX1 was more sensitive than cytology and HPV16/18 genotyping in detecting a HG lesion (CIN2+). The sensitivity for PAX1, SOX1, cytology and HPV16/18 were 73.5% (95% CI: 65.5–81.5), 41.9% (95% CI: 32.9–50.8), 48.7% (95% CI: 39.7–57.8) and 36.8% (95% CI: 28.0–45.5), respectively, and their respective specificities were 70.3% (95% CI: 65.0–75.6), 83.6% (95% CI: 79.3–87.9), 77.6% (95% CI: 72.8–82.5) and 67.1% (95% CI: 61.7–72.6), respectively. Overall, PAX1 gave the best AUC at 0.72. Adding SOX1 to PAX1 did not improve the AUC (0.68). Three hundred and twenty‐two women who did not have a HG lesion at baseline were followed up for two rounds of screening. Fewer women developed a HG lesion with a normal baseline PAX1 compared to women with a normal baseline cytology or negative HPV16/18 (8.4% vs. 14.5% and 17.5%, respectively). Conclusion: PAX1 triage for referral to colposcopy in HPV‐positive women may be superior to cytology and HPV16/18 genotyping. [ABSTRACT FROM AUTHOR]

Background: Anal HPV infection can cause squamous intraepithelial lesions (SILs), which are precursors of anal squamous cell carcinoma (SCC). The early detection of HPV infections and improvement of effective screening programmes are, therefore, essential to prevent progression from pre-cancerous lesions to SCC, especially in people living with HIV (PLWH), who represent a population at higher risk of HPV infection and associated lesions. Among prevention strategies, HPV vaccination is relevant too, but its efficacy in persons already infected by HPV is still debated. Methods: This is a retrospective single-center study on a cohort of PLWH who performed longitudinal screening for anal dysplasia and HPV infection. The screening included cytological and molecular analyses. Results: A total of 110 PLWH performed at least one anal HPV screening, with an overall prevalence of HPV infection of 86.4% [23.6% low risk (LR)-HPV and 62.7% high risk (HR)-HPV genotypes]. Abnormal cytology was demonstrated in 39.1% of subjects, of whom ASCUS 6.4%, LSIL 30.9% and HSIL 1.8%. In total, 80 patients (72.7%) had an available longitudinal screening. No patient developed SCC during follow-up. However, a high incidence of new cytological abnormalities and new HPV infections was observed. On the other side, clearance of some HPV genotypes was also frequent, confirming that HPV infection is a dynamic process. A CD4 cell count > 500/mmc was an independent predictor of HPV clearance. HPV vaccination was performed on 30.9% of patients. A trend toward an increased clearance of HPV genotypes included in 9-valent vaccine was observed in vaccinated patients (40.6% versus 30.8% in unvaccinated, p = 0.079). Conclusions: A high prevalence of HPV infection and SILs was observed in our cohort of PLWH. A high incidence of new HPV infections and HPV-associated lesions was also observed in the longitudinal cohort, highlighting the need of strengthening immunization programs and continuous screening for anal HPV infection. Whether HPV vaccination may be efficacious in patients already infected by HPV remains to be determined. [ABSTRACT FROM AUTHOR]

Simple Summary: Multiple myeloma (MM) is a plasma cell malignancy that develops in the bone marrow (BM) and the second-most-common blood cancer. Group 2 innate lymphoid cells (ILC2s) are emerging cytolytic immune effectors showing potent antitumor activity. In MM patients, ILC2s from peripheral blood possessed a cytotoxic arsenal, enabling them to kill MM cells via DNAM-1. In contrast, ILC2 resident in BM did not exert anti-myeloma activity, and instead became more susceptible to apoptosis. Specifically, MM cells led to ILC2 cell death by inducing and engaging the inhibitory receptor TIGIT. Collectively, ILC2s from MM patients displayed an imbalance in the DNAM-1/TIGIT axis, resulting in the conversion from a cytolytic to an exhausted profile. These findings support the employment of anti-TIGIT mAb to restore the survival and antitumor effects of ILC2s in MM. Background: Growing evidence attests to the multifaceted roles of group 2 innate lymphoid cells (ILC2s) in cancer immunity. They exhibit either pro- or anticancer activity depending on tumor type but their function in Multiple Myeloma (MM) is still not elucidated. Methods: The bone marrow (BM) and peripheral blood (PB) of patients (pts) with MM or precancerous conditions were collected, and specific properties of ILC2 subsets were assessed by flow cytometry. Results: By dissecting ILC2s according to c-Kit marker, we observed that NKp30 and NKG2D were mainly confined to c-Kithi ILC2s, while levels of DNAM-1 was significantly higher in fully mature c-Kitlo cells. Among the total MM-associated ILC2s (MM-ILC2s), we observed a significant increase in c-the Kitlo subset, but the expression of DNAM-1 in these cells was significantly reduced, especially in BM. Interestingly, MM-ILC2s from PB expressed granzyme B (GZMB), but its expression was impaired in BM-ILC2s. Accordingly, MM cells were susceptible to killing by MM-ILC2s derived from PB while eluding ILC2 surveillance in BM. Indeed, in MM-ILC2s derived from BM, the downregulation of DNAM-1 is accompanied by the upregulation of TIGIT, which mediate cell death in ILC2s upon recognition of the cognate ligands expressed by MM cells. These ILC2 changes appeared in clinical precursor conditions and eventually accumulated with disease progression. Conclusions: MM-ILC2s can act as cytolytic immune effectors that are fully competent in PB. However, MM cells shift ILC2 fate towards cell death in BM via the upregulation of TIGIT, thereby representing a potential therapeutic target to restore ILC2 antitumor activity. [ABSTRACT FROM AUTHOR]