Effort Required and Lessons Learned From Recruiting Health Plans and Rural Primary Care Practices for a Cancer Screening Outreach Study.

INTRODUCTION: Recruiting organizations (i.e., health plans, health systems, or clinical practices) is important for implementation science, yet limited research explores effective strategies for engaging organizations in pragmatic studies. We explore the effort required to meet recruitment targets for a pragmatic implementation trial, characteristics of engaged and non-engaged clinical practices, and reasons health plans and rural clinical practices chose to participate. METHODS: We explored recruitment activities and factors associated with organizational enrollment in SMARTER CRC, a randomized pragmatic trial to increase rates of CRC screening in rural populations. We sought to recruit 30 rural primary care practices within participating Medicaid health plans. We tracked recruitment outreach contacts, meeting content, and outcomes using tracking logs. Informed by the Consolidated Framework for Implementation Research, we analyzed interviews, surveys, and publicly available clinical practice data to identify facilitators of participation. RESULTS: Overall recruitment activities spanned January 2020 to April 2021. Five of the 9 health plans approached agreed to participate (55%). Three of the health plans chose to operate centrally as 1 site based on network structure, resulting in 3 recruited health plan sites. Of the 101 identified practices, 76 met study eligibility criteria; 51% (n = 39) enrolled. Between recruitment and randomization, 1 practice was excluded, 5 withdrew, and 7 practices were collapsed into 3 sites for randomization purposes based on clinical practice structure, leaving 29 randomized sites. Successful recruitment required iterative outreach across time, with a range of 2 to 17 encounters per clinical practice. Facilitators to recruitment included multi-modal outreach, prior relationships, effective messaging, flexibility, and good timing. CONCLUSION: Recruiting health plans and rural clinical practices was complex and iterative. Leveraging existing relationships and allocating time and resources to engage clinical practices in pragmatic implementation research may facilitate more diverse representation in future trials and generalizability of research findings.

[Development and validation of predictive models for esophageal squamous cell carcinoma and its precancerous lesions using terminal motif analysis in circulating cell-free DNA].

Objectives: To develop and validate predictive models for esophageal squamous cell carcinoma (ESCC) using circulating cell-free DNA (cfDNA) terminal motif analysis. The goal was to improve the non-invasive detection of early-stage ESCC and its precancerous lesions. Methods: Between August 2021 and November 2022, we prospectively collected plasma samples from 448 individuals at the Department of Endoscopy, Cancer Hospital, Chinese Academy of Medical Sciences for cfDNA extraction, library construction, and sequencing. We analyzed 201 cases of ESCC, 46 high-grade intraepithelial neoplasia (HGIN), 46 low-grade intraepithelial neoplasia (LGIN), 176 benign esophageal lesions, and 29 healthy controls. Participants, including ESCC patients and control subjects, were randomly assigned to a training set (n=284) and a validation set (n=122). The training cohort underwent z-score normalization of cfDNA terminal motif matrices and a selection of distinctive features differentiated ESCC cases from controls. The random forest classifier, Motif-1 (M1), was then developed through principal component analysis, ten-fold cross-validation, and recursive feature elimination. M1's efficacy was then validated in the validation and precancerous lesion sets. Subsequently, individuals with precancerous lesions were included in the dataset and participants were randomly allocated to newly formed training (n=243), validation (n=105), and test (n=150) cohorts. Using the same procedure as M1, we trained the Motif-2 (M2) random forest model with the training cohort. The M2 model's accuracy was then confirmed in the validation cohort to establish the optimal threshold and further tested by performing validation in the test cohort. Results: We developed two cfDNA terminal motif-based predictive models for ESCC and associated precancerous conditions. The first model, M1, achieved a sensitivity of 90.0%, a specificity of 77.4%, and an area under the curve (AUC) of 0.884 in the validation cohort. For LGIN, HGIN, and T1aN0 stage ESCC, M1's sensitivities were 76.1%, 80.4%, and 91.2% respectively. Notably, the sensitivity for jointly predicting HGIN and T1aN0 ESCC reached 85.0%. Both the predictive accuracy and sensitivity increased in line with the cancer's progression (P＜0.001). The second model, M2, exhibited a sensitivity of 87.5%, a specificity of 77.4%, and an AUC of 0.857 in the test cohort. M2's sensitivities for detecting precancerous lesions and ESCC were 80.0% and 89.7%, respectively, and it showed a combined sensitivity of 89.4% for HGIN and T1aN0 stage ESCC. Conclusions: Two predictive models based on cfDNA terminal motif analysis for ESCC and its precancerous lesions are developed. They both show high sensitivity and specificity in identifying ESCC and its precancerous stages, indicating its potential for early ESCC detection.

Screening for Lung Cancer in India: Expert Opinion Statement.

Lung cancer (LC) has the highest rate of disability-adjusted life years (DALY) of all cancers in India. A large majority of patients with LC present with advanced disease, resulting in poor survival rates. Early diagnosis can improve survival outcomes as the patients can be treated with curative intent. The National Lung Screening Trial (NLST), in 53,454 persons at high risk for LC in the US, showed a 20% (95% confidence interval of 6.8-26.7; p = 0.004) relative reduction in LC-specific mortality in the patients screened with low-dose computed tomography (LDCT) compared with chest X-ray. To date, India does not have a formal LC screening (LCS) program. As a panel of experts, we reviewed a synthesis of a targeted literature search on the burden of LC, the current status of diagnosis of LC, barriers to early diagnosis, current referral pathways, LC risk patterns, use of artificial intelligence (AI) and risk calculators for risk assessment, and a multidisciplinary team (MDT) approach to diagnosis LC. We used the existing international LCS guidelines, data from published literature, and clinical experience to depict the characteristics of the population at risk of LC in India-young age (<40 years), smoking, especially the predominance of bidi smoking (an indigenous form of tobacco smoking), exposure to biomass fuel smoke, especially in rural women, and air pollution being the prominent features. LC in India is characterized by a higher rate of driver mutations and adenocarcinomatous histology. Here, we present the expert opinion on risk-based LCS in India and discuss the challenges, facilitators, and research priorities for the effective rollout of LCS in India.

Multi-dimensional cell-free DNA-based liquid biopsy for sensitive early detection of gastric cancer.

BACKGROUND: Gastric cancer is the fifth most common cancer type. Most patients are diagnosed at advanced stages with poor prognosis. A non-invasive assay for the detection of early-stage gastric cancer is highly desirable for reducing associated mortality. METHODS: We collected a prospective study cohort of 110 stage I-II gastric cancer patients and 139 non-cancer individuals. We performed whole-genome sequencing with plasma samples and profiled four types of cell-free DNA (cfDNA) characteristics, fragment size pattern, copy number variation, nucleosome coverage pattern, and single nucleotide substitution. With these differential profiles, we developed an ensemble model to detect gastric cancer signals. Further, we validated the assay in an in-house first validation cohort of 73 gastric cancer patients and 94 non-cancer individuals and an independent second validation cohort of 47 gastric cancer patients and 49 non-cancer individuals. Additionally, we evaluated the assay in a hypothetical 100,000 screening population by Monte Carlo simulation. RESULTS: Our cfDNA-based assay could distinguish early-stage gastric cancer from non-cancer at an AUROC of 0.962 (95% CI: 0.942-0.982) in the study cohort, 0.972 (95% CI: 0.953-0.992) in the first validation cohort and 0.937 (95% CI: 0.890-0.983) in the second validation cohort. The model reached a specificity of 92.1% (128/139) and a sensitivity of 88.2% (97/110) in the study cohort. In the first validation cohort, 91.5% (86/94) of non-cancer individuals and 91.8% (67/73) of gastric cancer patients were correctly identified. In the second validation cohort, 89.8% (44/49) of non-cancer individuals and 87.2% (41/47) of gastric cancer patients were accurately classified. CONCLUSIONS: We introduced a liquid biopsy assay using multiple dimensions of cfDNA characteristics that could accurately identify early-stage gastric cancer from non-cancerous conditions. As a cost-effective non-invasive approach, it may provide population-wide benefits for the early detection of gastric cancer. TRIAL REGISTRATION: This study was registered on ClinicalTrials.gov under the identifier NCT05269056 on March 7, 2022.

Early detection of pancreatic cancer by liquid biopsy "PANLIPSY": a french nation-wide study project.

BACKGROUND: Pancreatic cancer, predominantly characterized by ductal adenocarcinoma (PDAC) accounts for 90% of cases and is the fourth leading cause of cancer-related deaths globally. Its incidence is notably increasing. This poor prognosis is primarily due to late-stage diagnosis (approximately 70% to 80% of patients are diagnosed at an advanced stage), aggressive tumor biology, and low sensitivity to chemotherapy. Consequently, it is crucial to identify and develop a simple, feasible and reproducible blood-based signature (i.e., combination of biomarkers) for early detection of PDAC. METHODS: The PANLIPSY study is a multi-center, non-interventional prospective clinical trial designed to achieve early detection of PDAC with high specificity and sensitivity, using a combinatorial approach in blood samples. These samples are collected from patients with resectable, borderline or locally advanced, and metastatic stage PDAC within the framework of the French Biological and Clinical Database for PDAC cohort (BACAP 2). All partners of the BACAP consortium are eligible to participate. The study will include 215 PDAC patients, plus 25 patients with benign pancreatic conditions from the PAncreatic Disease Cohort of TOuLouse (PACTOL) cohort, and 115 healthy controls, totaling 355 individuals. Circulating biomarkers will be collected in a total volume of 50 mL of blood, divided into one CellSave tube (10 mL), two CELL-FREE DNA BCT® preservative tubes (18 mL), and five EDTA tubes (22 mL in total). Samples preparation will adhere to the guidelines of the European Liquid Biopsy Society (ELBS). A unique feature of the study is the AI-based comparison of these complementary liquid biopsy biomarkers. Main end-points: i) to define a liquid biopsy signature that includes the most relevant circulating biomarkers, ii) to validate the multi-marker panel in an independent cohort of healthy controls and patients, with resectable PDAC, and iii) to establish a unique liquid biopsy biobank for PDAC study. DISCUSSION: The PANLIPSY study is a unique prospective non-interventional clinical trial that brings together liquid biopsy experts. The aim is to develop a biological signature for the early detection of PDAC based on AI-assisted detection of circulating biomarkers in blood samples (CTCs, ctDNA, EVs, circulating immune system, circulating cell-free nucleosomes, proteins, and microbiota). TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT06128343 / NCT05824403. Registration dates: June 8,2023 and April 21, 2023.

Impact of annual trend volume of low-dose computed tomography for lung cancer screening on overdiagnosis, overmanagement, and gender disparities.

BACKGROUND: With the increasing prevalence of nonsmoking-related lung cancer in Asia, Asian countries have increasingly adopted low-dose computed tomography (LDCT) for lung cancer screening, particularly in private screening programs. This study examined how annual LDCT volume affects lung cancer stage distribution, overdiagnosis, and gender disparities using a hospital-based lung cancer database. METHODS: This study analyzed the annual utilized LDCT volume, clinical characteristics of lung cancer, stage shift distribution, and potential overdiagnosis. At the individual level, this study also investigated the relationship between stage 0 lung cancer (potential strict definition regarding overdiagnosis) and the clinical characteristics of lung cancer. RESULTS: This study reviewed the annual trend of 4971 confirmed lung cancer cases from 2008 to 2021 and conducted a link analysis with an LDCT imaging examination database over these years. As the volume of lung cancer screenings has increased over the years, the number and proportion of stage 0 lung cancers have increased proportionally. Our study revealed that the incidence of stage 0 lung cancer increased with increasing LDCT scan volume, particularly during the peak growth period from 2017 to 2020. Conversely, stage 4 lung cancer cases remained consistent across different time intervals. Furthermore, the increase in the lung cancer screening volume had a more pronounced effect on the increase in stage 0 lung cancer cases among females than it had among males. The estimated potential for overdiagnosis brought about by the screening process, compared to non-participating individuals, ranged from an odds ratio of 7.617 to one of 17.114. Both strict and lenient definitions of overdiagnosis (evaluating cases of stage 0 lung cancer and stages 0 to 1 lung cancer) were employed. CONCLUSIONS: These results provide population-level evidence of potential lung cancer overdiagnosis in the Taiwanese population due to the growing use of LDCT screening, particularly concerning the strict definition of stage 0 lung cancer. The impact was greater in the female population than in the male population, especially among females younger than 40 years. To improve lung cancer screening in Asian populations, creating risk-based prediction models for smokers and nonsmokers, along with gender-specific strategies, is vital for ensuring survival benefits and minimizing overdiagnosis.

[Interest in the use of polygenic risk scores in breast cancer screening and preventive medicine]. / Intérêt de l'utilisation des scores de risques polygéniques dans le dépistage du cancer du sein et la médecine de prévention.

Despite screening programmes, numerous clinical studies and new breast imaging techniques, breast cancer incidence for women continues to rise. The arrival of predictive and personalized medicine could clearly redefine our screening recommendations. One promising approach to improving screening would be to use tools to predict the risk of developing breast cancer, including polygenic risk scores (PRS). This approach will enable us to offer women risk-based screening by adapting the frequency, type and age of screening. This article reviews some definitions of the PRS and breast cancer screening. We also explain the risk assessment models that have been developed and the various studies underway on personalized screening.

Malgré les programmes de dépistage, les nombreuses études cliniques et les nouvelles techniques d'imagerie mammaire, l'incidence du cancer du sein chez la femme continue à augmenter. L'arrivée de la médecine prédictive et personnalisée pourrait clairement redéfinir nos recommandations de dépistage. Une des approches prometteuses pour améliorer le dépistage serait d'utiliser les outils de prédiction du risque de développer un cancer du sein en incluant les scores de risques polygéniques (PRS). Cette approche permettra de proposer aux femmes un dépistage basé sur le risque en adaptant la fréquence des examens ainsi que le type et l'âge du début du dépistage. Cet article reprend quelques définitions concernant le PRS et le dépistage du cancer sein. Nous allons passer en revue les modèles de prédiction de risque qui ont été développés et les différentes études en cours sur le dépistage personnalisé.

An improved approach for automated cervical cell segmentation with PointRend.

Regular screening for cervical cancer is one of the best tools to reduce cancer incidence. Automated cell segmentation in screening is an essential task because it can present better understanding of the characteristics of cervical cells. The main challenge of cell cytoplasm segmentation is that many boundaries in cell clumps are extremely difficult to be identified. This paper proposes a new convolutional neural network based on Mask RCNN and PointRend module, to segment overlapping cervical cells. The PointRend head concatenates fine grained features and coarse features extracted from different feature maps to fine-tune the candidate boundary pixels of cell cytoplasm, which are crucial for precise cell segmentation. The proposed model achieves a 0.97 DSC (Dice Similarity Coefficient), 0.96 TPRp (Pixelwise True Positive Rate), 0.007 FPRp (Pixelwise False Positive Rate) and 0.006 FNRo (Object False Negative Rate) on dataset from ISBI2014. Specially, the proposed method outperforms state-of-the-art result by about 3 % on DSC, 1 % on TPRp and 1.4 % on FNRo respectively. The performance metrics of our model on dataset from ISBI2015 are slight better than the average value of other approaches. Those results indicate that the proposed method could be effective in cytological analysis and then help experts correctly discover cervical cell lesions.

Exosomes multiplex profiling, a promising strategy for early diagnosis of laryngeal cancer.

BACKGROUND: Exosomes are nanosized vesicles released from all cells into surrounding biofluids, including cancer cells, and represent a very promising direction in terms of minimally invasive approaches to early disease detection. They carry tumor-specific biological contents such as DNA, RNA, proteins, lipids, and sugars, as well as surface molecules that are able to pinpoint the cellular source. By the above criteria, exosomes may be stratified according to the presence of tissue and disease-specific signatures and, due to their stability in such biofluids as plasma and serum, they represent an indispensable source of vital clinical insights from liquid biopsies, even at the earliest stages of cancer. Therefore, our work aimed to isolate and characterize LCa patients' derived exosomes from serum by Flow Cytometry in order to define a specific epitope signature exploitable for early diagnosis. METHODS: Circulating exosomes were collected from serum collected from 30 LCa patients and 20 healthy volunteers by the use of antibody affinity method exploiting CD63 specific surface marker. Membrane epitopes were then characterized by Flow cytometry multiplex analysis and compared between LCa Patients and Healthy donors. Clinical data were also matched to obtain statistical correlation. RESULTS: A distinct overexpression of CD1c, CD2, CD3, CD4, CD11c, CD14, CD20, CD44, CD56, CD105, CD146, and CD209 was identified in LCa patients compared to healthy controls, correlating positively with tumor presence. Conversely, CD24, CD31, and CD40, though not overexpressed in tumor samples, showed a significant correlation with nodal involvement in LCa patients (p < 0.01). CONCLUSION: This approach could allow us to set up a cost-effective and less invasive liquid biopsy protocol from a simple blood collection in order to early diagnose LCa and improve patients' outcomes and quality of life.

Recurrent disease detection after resection of pancreatic ductal adenocarcinoma using a recurrence-focused surveillance strategy (RADAR-PANC): protocol of an international randomized controlled trial according to the Trials within Cohorts design.

BACKGROUND: Disease recurrence remains one of the biggest concerns in patients after resection of pancreatic ductal adenocarcinoma (PDAC). Despite (neo)adjuvant systemic therapy, most patients experience local and/or distant PDAC recurrence within 2 years. High-level evidence regarding the benefits of recurrence-focused surveillance after PDAC resection is missing, and the impact of early detection and treatment of recurrence on survival and quality of life is unknown. In most European countries, recurrence-focused follow-up after surgery for PDAC is currently lacking. Consequently, guidelines regarding postoperative surveillance are based on expert opinion and other low-level evidence. The recent emergence of more potent local and systemic treatment options for PDAC recurrence has increased interest in early diagnosis. To determine whether early detection and treatment of recurrence can lead to improved survival and quality of life, we designed an international randomized trial. METHODS: This randomized controlled trial is nested within an existing prospective cohort in pancreatic cancer centers in the Netherlands (Dutch Pancreatic Cancer Project; PACAP) and the United Kingdom (UK) (Pancreas Cancer: Observations of Practice and survival; PACOPS) according to the "Trials within Cohorts" (TwiCs) design. All PACAP/PACOPS participants with a macroscopically radical resection (R0-R1) of histologically confirmed PDAC, who provided informed consent for TwiCs and participation in quality of life questionnaires, are included. Participants randomized to the intervention arm are offered recurrence-focused surveillance, existing of clinical evaluation, serum cancer antigen (CA) 19-9 testing, and contrast-enhanced computed tomography (CT) of chest and abdomen every three months during the first 2 years after surgery. Participants in the control arm of the study will undergo non-standardized clinical follow-up, generally consisting of clinical follow-up with imaging and serum tumor marker testing only in case of onset of symptoms, according to local practice in the participating hospital. The primary endpoint is overall survival. Secondary endpoints include quality of life, patterns of recurrence, compliance to and costs of recurrence-focused follow-up, and the impact on recurrence-focused treatment. DISCUSSION: The RADAR-PANC trial will be the first randomized controlled trial to generate high level evidence for the current clinical equipoise regarding the value of recurrence-focused postoperative surveillance with serial tumor marker testing and routine imaging in patients after PDAC resection. The Trials within Cohort design allows us to study the acceptability of recurrence-focused surveillance among cohort participants and increases the generalizability of findings to the general population. While it is strongly encouraged to offer all trial participants treatment at time of recurrence diagnosis, type and timing of treatment will be determined through shared decision-making. This might reduce the potential survival benefits of recurrence-focused surveillance, although insights into the impact on patients' quality of life will be obtained. TRIAL REGISTRATION: Clinicaltrials.gov, NCT04875325 . Registered on May 6, 2021.

Nanoenzymes: A Radiant Hope for the Early Diagnosis and Effective Treatment of Breast and Ovarian Cancers.

Breast and ovarian cancers, despite having chemotherapy and surgical treatment, still have the lowest survival rate. Experimental stages using nanoenzymes/nanozymes for ovarian cancer diagnosis and treatment are being carried out, and correspondingly the current treatment approaches to treat breast cancer have a lot of adverse side effects, which is the reason why researchers and scientists are looking for new strategies with less side effects. Nanoenzymes have intrinsic enzyme-like activities and can reduce the shortcomings of naturally occurring enzymes due to the ease of storage, high stability, less expensive, and enhanced efficiency. In this review, we have discussed various ways in which nanoenzymes are being used to diagnose and treat breast and ovarian cancer. For breast cancer, nanoenzymes and their multi-enzymatic properties can control the level of reactive oxygen species (ROS) in cells or tissues, for example, oxidase (OXD) and peroxidase (POD) activity can be used to generate ROS, while catalase (CAT) or superoxide dismutase (SOD) activity can scavenge ROS. In the case of ovarian cancer, most commonly nanoceria is being investigated, and also when folic acid is combined with nanoceria there are additional advantages like inhibition of beta galactosidase. Nanocarriers are also used to deliver small interfering RNA that are effective in cancer treatment. Studies have shown that iron oxide nanoparticles are actively being used for drug delivery, similarly ferritin carriers are used for the delivery of nanozymes. Hypoxia is a major factor in ovarian cancer, therefore MnO2-based nanozymes are being used as a therapy. For cancer diagnosis and screening, nanozymes are being used in sonodynamic cancer therapy for cancer diagnosis and screening, whereas biomedical imaging and folic acid gold particles are also being used for image guided treatments. Nanozyme biosensors have been developed to detect ovarian cancer. This review article summarizes a detailed insight into breast and ovarian cancers in light of nanozymes-based diagnostic and therapeutic approaches.

Colorectal cancer screening with fecal immunochemical testing or primary colonoscopy: inequities in diagnostic yield.

BACKGROUND: Socioeconomic inequalities in the uptake of colorectal cancer screening are well documented, but the implications on inequities in health gain remain unclear. METHODS: Sixty-year-olds were randomly recruited from the Swedish population between March 2014 and March 2020 and invited to undergo either 2 rounds of fecal immunochemical testing (FIT) 2 years apart (n = 60 137) or primary colonoscopy just once (n = 30 400). By linkage to Statistics Sweden's registries, we obtained socioeconomic data. In each defined socioeconomic group, we estimated the cumulative yield of advanced neoplasia in each screening arm (intention-to-screen analysis). In the biennial FIT arm, we predicted the probability of exceeding the yield in the primary colonoscopy arm by linear extrapolation of the cumulative yield to (hypothetical) additional rounds of FIT. RESULTS: In the lowest income group, the yield of advanced neoplasia was 1.63% (95% confidence interval [CI] = 1.35% to 1.93%) after 2 rounds of FIT vs 1.93% (95% CI = 1.49% to 2.40%) in the primary colonoscopy arm. Extrapolation to a third round of FIT implied a 86% probability of exceeding the yield in the primary colonoscopy arm. In the highest income group, we found a more pronounced yield gap between the 2 screening strategies-2.32% (95% CI = 2.15% to 2.49%) vs 3.71% (95% CI = 3.41% to 4.02%)- implying a low (2%) predicted probability of exceeding yield after a third round of FIT. CONCLUSIONS: Yield of advanced neoplasia from 2 rounds of FIT 2 years apart was poorer as compared with primary colonoscopy, but the difference was less in lower socioeconomic groups. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02078804.

Performance of CADM1, MAL and miR124-2 methylation as triage markers for early detection of cervical cancer in self-collected and clinician-collected samples: an exploratory observational study in Papua New Guinea.

OBJECTIVE: WHO recommends human papillomavirus (HPV) testing for cervical screening, with triage of high-risk HPV (hrHPV) positive women. However, there are limitations to effective triage for low-resource, high-burden settings, such as Papua New Guinea. In this exploratory study, we assessed the performance of host methylation as triage tools for predicting high-grade squamous intraepithelial lesions (HSIL) in self-collected and clinician-collected samples. DESIGN: Exploratory observational study. SETTING: Provincial hospital, same-day cervical screen-and-treat trial, Papua New Guinea. PARTICIPANTS: 44 hrHPV+women, with paired self/clinician-collected samples (4 squamous cell carcinomas (SCC), 19 HSIL, 4 low-grade squamous intraepithelial lesions, 17 normal). PRIMARY AND SECONDARY OUTCOME MEASURES: Methylation levels of CADM1, MAL and miR124-2 analysed by methylation-specific PCRs against the clinical endpoint of HSIL or SCC (HSIL+) measured using liquid-based-cytology/p16-Ki67 stain. RESULTS: In clinician-collected samples, MAL and miR124-2 methylation levels were significantly higher with increasing grade of disease (p=0.0046 and p<0.0015, respectively). miR124-2 was the best predictor of HSIL (area under the curve, AUC 0.819) while MAL of SCC (AUC 0.856). In self-collected samples, MAL best predicted HSIL (AUC 0.595) while miR124-2 SCC (AUC 0.812). Combined miR124-2/MAL methylation yielded sensitivity and specificity for HSIL+ of 90.5% (95% CI 69.6% to 98.8%) and 70% (95% CI 45.7% to 88.1%), respectively, in clinician-collected samples, and 81.8% (95% CI 59.7% to 94.8%) and 47.6% (95% CI 25.7% to 70.2%), respectively, in self-collected samples. miR124-2/MAL plus HPV16/HPV18 improved sensitivity for HSIL+ (95.2%, 95% CI 76.2% to 99.9%) but decreased specificity (55.0%, 95% CI 31.5% to 76.9%). CONCLUSION: miR124-2/MAL methylation is a potential triage strategy for the detection of HSIL/SCC in low-income and middle-income country.

A Four-Gene Panel in Rectal Swab Samples as a Biomarker for Colorectal Cancer Screening.

BACKGROUND: The dysregulation of gene expression is one of the key molecular features of colorectal cancer (CRC) development. This study aimed to investigate whether such dysregulation is reflected in rectal swab specimens of CRC patients and to evaluate its potential as a non-invasive approach for screening. METHODS: We compared the expression level of 14 CRC-associated genes in tumor and adjacent non-tumor tissue of CRC patients and examined the correlation of their levels in tissue with paired rectal swab specimens. The level of these 14 genes in rectal swab specimens was compared among patients with CRC or polyp and control subjects, and the diagnostic potential of each dysregulated gene and the gene panel were evaluated. RESULTS: The expression of CXCR2, SAA, COX1, PPARδ, PPARγ, Groγ, IL8, p21, c-myc, CD44 and CSF1 was significantly higher in CRC, and there was a significant correlation in the levels of most of them between the CRC and rectal swab specimens. In the training study, we showed that CD44, IL8, CXCR2 and c-myc levels were significantly higher in the rectal swab specimens of the CRC patients. Such result was confirmed in the validation study. A panel of these four genes was developed, and ROC analysis showed that this four-gene panel could identify CRC patients with an AUC value of 0.83 and identify overall polyp and precancerous adenoma patients with AUC values of 0.6522 and 0.7322, respectively. Finally, the predictive study showed that the four-gene panel demonstrated sensitivities of 63.6%, 76.9% and 88.9% in identifying overall polyp, precancerous adenoma and CRC patients, respectively, whereas the specificity for normal subjects was 72.2%. CONCLUSION: The expression of CRC-associated genes in rectal swab specimens reflects the dysregulation status in colorectal tissue, and the four-gene panel is a potential non-invasive biomarker for early precancerous adenoma and CRC screening.

Infrared Spectroscopy in Gynecological Oncology: A Comprehensive Review of Diagnostic Potentials and Challenges.

The early detection of gynecological cancers, which is critical for improving patient survival rates, is challenging because of the vague early symptoms and the diagnostic limitations of current approaches. This comprehensive review delves into the game-changing potential of infrared (IR) spectroscopy, a noninvasive technology used to transform the landscape of cancer diagnosis in gynecology. By collecting the distinctive vibrational frequencies of chemical bonds inside tissue samples, Fourier-transform infrared (FTIR) spectroscopy provides a 'molecular fingerprint' that outperforms existing diagnostic approaches. We highlight significant advances in this field, particularly the identification of discrete biomarker bands in the mid- and near-IR spectra. Proteins, lipids, carbohydrates, and nucleic acids exhibited different absorption patterns. These spectral signatures not only serve to distinguish between malignant and benign diseases, but also provide additional information regarding the cellular changes associated with cancer. To underscore the practical consequences of these findings, we examined studies in which IR spectroscopy demonstrated exceptional diagnostic accuracy. This review supports the use of IR spectroscopy in normal clinical practice, emphasizing its capacity to detect and comprehend the intricate molecular underpinnings of gynecological cancers.