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Background: Biomarkers have revolutionized the management of colorectal cancer (CRC), facilitating early detection, prevention, personalized treatment, and minimal residual disease (MRD) monitoring. This review explores current CRC screening strategies and emerging biomarker applications., Main Body: We summarize the landscape of non-invasive CRC screening and MRD detection strategies, discuss the limitations of the current approaches, and highlight the promising potential of novel biomarker solutions. The fecal immunochemical test remained the cornerstone of CRC screening, but its sensitivity has been improved by assays that combined its performance with other stool analytes. However, their sensitivity for advanced adenomas and the patient compliance both remain suboptimal. Blood-based tests promise to increase compliance but require further refinement to compete with stool-based biomarker tests. The ideal scenario involves leveraging blood tests to increase screening participation, and simultaneously promote stool- and endoscopy-based screening among those who are compliant. Once solely reliant on upfront surgery followed by stage and pathology-driven adjuvant chemotherapy, the treatment of stage II and III colon cancer has undergone a revolutionary transformation with the advent of MRD testing after surgery. A decade ago, the concept of using a post-surgical test instead of stage and pathology to determine the need for adjuvant chemotherapy was disruptive. Today, a blood test may be more informative of the need for chemotherapy than the stage at diagnosis., Conclusion: Biomarker research is not just improving, but bringing a transformative change to CRC clinical management. Early detection is not just getting better, but improving thanks to a multi-modality approach, and personalized treatment plans are not just becoming a reality, but a promising future with MRD testing., Competing Interests: Declarations Ethics approval and consent to participate Not applicable. Consent to participate Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: Colonoscopy as a common screening practice to prevent colorectal cancer lacks strong evidence. NordICC, the first randomized trial of colonoscopy screening, reported no clear clinical benefit for colonoscopy in the intention-to-screen population with suggested benefit in the risk of colorectal incidence and cancer-specific mortality in the per-protocol analyses. However, although the study was designed to perform survival analysis, no survival outcomes were reported since the underlying assumption for hazard ratio was not valid. We aimed to assess whether colonoscopy screening is associated with improved survival outcomes compared with usual care., Methods: We reconstructed patient-level data from the Kaplan-Meier estimator of the primary endpoints reported in NordICC for the intention-to-screen and adjusted per-protocol populations. The restricted-mean survival time difference (RMST-D) and restricted-mean time loss ratio (RMTL-R), which are robust alternatives to the hazard ratio without specific model assumptions, were calculated for colorectal cancer incidence and death., Results: In this study, no significant difference in colorectal cancer incidence over 10 years was found in the intention-to-screen population (RMST-D: -0.68 days, 95% CI -3.9-2.6; RMTL-R: 1.04, 95% CI 0.88-1.22) or in the per-protocol analysis population (RMST-D: -2.9 days, 95% CI -6.5-0.67; RMTL-R: 1.15, 95% CI 0.97-1.35). In the intention-to-screen population, inviting individuals to colonoscopy did not improve colorectal-cancer death (RMST-D: -0.29 days, 95% CI -1.6-1.0; RMTL-R: 1.07, 95% CI 0.78-1.48). Over 10 years, in the per-protocol analysis, individuals who underwent colonoscopy survived an average of 1.1 more days free of colorectal cancer, but this difference was not statistically significant (RMST-D: 95% CI -0.13-2.3; RMTL-R: 0.72, 95% CI 0.49-1.07)., Conclusions: In this reanalysis of the NordICC data, no evidence of improvement in survival outcomes for participants invited to undergo colonoscopy compared to usual care was identified, even when assuming that all invited participants did undergo colonoscopy. Thus, our results do not support the use of colonoscopy as a population-wide screening test as a mean to decrease colorectal cancer incidence or death., Registry: Not applicable., Competing Interests: Declarations Ethics approval and consent to participate Not applicable. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: The aim of this quality improvement (QI) project was to increase Colorectal Cancer (CRC) screening in patients ages 50-75 years from a baseline of 27-40% within 12 months in a primary care clinic in limited resource communities., Methods: The multidisciplinary QI-team applied the Plan-Do-Study-Act method and developed stakeholder analysis, an Ishikawa fish bone diagram, a process flow map, and a driver diagram. Major barriers to suboptimal CRC screening included limited health literacy, language preferences, absence of stool test options, and knowledge gaps among patients and providers. The outcome measure was CRC screening rates, while stool test and colonoscopy completion rates served as process measures. Major interventions included the use of a patient-navigator, leveraging digital health technology to create a novel CRC screening data dashboard, educating patients and providers, patient centered-shared decision making, and creating messages and educational videos in patient's preferred languages. We used monthly run charts and statistical process control charts (SPC) for data analysis., Results: We observed a sustainable, steady increase in CRC screening rates from baseline rates of 27.0-40.0% (n = 1304/3271) during the study period and 45.6% (n = 1493/3,271) six months post-study, with median rates of 34.0% in the run chart and mean rates of 43.0% in the SPC chart. Furthermore, we observed an increase in colonoscopy completion rates during the study and six months post-study to 65.0% (n = 411/631) and 72.9% (n = 461/631) respectively, from a baseline rate of 25.0%, with a median of 63.0% in the monthly run chart., Conclusion: The increase in CRC screening rates highlights the effectiveness of addressing barriers such as health literacy, language preferences, and knowledge gaps. This underscores the value of a multifaceted approach and the role of a patient navigator in enhancing preventive, patient-centered care. This project focused on population health and addressing social determinants of health to overcome disparities and improve CRC screening in a primary care setting. Continued emphasis on these strategies is likely to further advance colorectal cancer screening efforts., Competing Interests: Declarations Ethics approval and consent to participate This study was reviewed by the University at Buffalo human subject institutional review board and was classified as exempt from human subjects. The University at Buffalo human subject institutional review board determined that the proposed activity is not research involving human subjects (Exempt). It was written and planned as a Quality Improvement project. STUDY00005976. Informed consent was waived by University at Buffalo human subject institutional review board. Survey was developed for this study. Consent for publication The University at Buffalo human subject institutional review board determined that the proposed activity is not research involving human subjects. Informed consent was waived by the University at Buffalo human subject institutional review board. No consent for publication necessary. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Purpose: The impact of the components of survivorship care plans on adherence to cancer screening guidelines among cancer survivors is limited. We examined the association of receipt of treatment summaries, follow-up instructions, and type of doctor providing survivorship care with adherence to breast cancer screening (BCS) and cervical cancer screening (CCS) guidelines in female cancer survivors., Methods: A cross-sectional analysis using Behavioral Risk Factor Surveillance System (BRFSS) data from 2014, 2016 and 2018 was conducted. BCS and CCS-eligible women were aged 40-74 and 30-64, respectively. BCS adherence was defined as a mammogram within 2 years and CCS adherence as a pap smear within 3 years or HPV test within 5 years. Univariate analysis with chi-square and multivariable logistic regression are reported., Results: 5,001 BCS and 3,014 CCS-eligible survivors were identified. In the BCS group, recipients of treatment summaries and follow-up instructions were significantly more adherent with BCS (84.1% vs. 77.4%; 83.4% vs. 74%, respectively, p < 0.001). In the CCS group, recipients of follow-up instructions were significantly more adherent with CCS (78.1% vs. 67.7%, p < 0.001). In both groups, there was no significant difference in BCS or CCS based on type of physician providing care (p = 0.087). On multivariate analysis, receipt of follow-up instructions was the only factor significantly associated with BCS (OR:2.81; 95%CI:1.76-4.49) and CCS (OR:3.14; 95%CI:1.88-5.23)., Conclusions: Follow-up instructions, as part of survivorship care plans, have the strongest association with BCS and CCS among female cancer survivors. Additional research should focus on improving the distribution of survivorship care plans, particularly follow-up instructions, as a method to increase BCS and CCS among cancer survivors., Competing Interests: Declarations Ethics approval This is an observational study with publicly available de-identified individual data and did not require approval from the Rutgers University Institutional Board Review. Competing interests The authors declare no competing interests. Disclaimers This research was presented as a poster at the 2023 ASCO Annual Meeting, held in Chicago, IL, June 2 to 6, 2023, and published as an abstract from the meeting., (© 2024. The Author(s).)

The specificity and sensitivity of a simple non-invasive multi-cancer screening method in detecting breast, lung, prostate, and colorectal cancer in breath samples were evaluated in a double-blind study. Breath samples of 1386 participants (59.7% males, median age 56.0 years) who underwent screening for cancer using gold-standard screening methods, or a biopsy for a suspected malignancy were collected. The samples were analyzed using a bio-hybrid platform comprising trained detection canines and artificial intelligence tools. According to cancer screening/biopsy results, 1048 (75.6%) were negative for cancer and 338 (24.4%) were positive. Among the 338 positive samples, 261 (77.2%) were positive for one of the four cancer types that the bio-hybrid platform was trained to detect, with an overall sensitivity and specificity of 93.9% (95% confidence interval [CI] 90.3-96.2%) and 94.3% (95% CI 92.7%-95.5%), respectively. The sensitivity of each cancer type was similar; breast: 95.0% (95% CI 87.8-98.0%), lung: 95.0% (95% CI 87.8-98.0%), colorectal: 90.0% (95% CI 74.4-96.5%), prostate: 93.0% (95% CI 84.6-97.0%). The sensitivity of 14 other malignant tumors that the bio-hybrid platform was not trained to detect, but identified, was 81.8% (95% CI 71.8%-88.8%). Early cancer (0-2) detection sensitivity was 94.8% (95% CI 91.0%-97.1%). This bio-hybrid multi-cancer screening platform demonstrated high sensitivity and specificity and enables early-stage cancer detection., Competing Interests: Declarations Competing interests Milana Avdalimov and Assaf Rabinowicz are SpotitEarly Ltd. employees. Sharon Furman-Assaf and Ronit Shmuel received funding from SpotitEarly Ltd. All other authors have no competing interests to declare., (© 2024. The Author(s).)

Whole-body MRI (WBMRI) is an integral part of screening infants, children, and adolescents for presymptomatic neoplasms in certain cancer predisposition syndromes, which include Li-Fraumeni and constitutional mismatch repair deficiency syndromes, among others. The list of syndromes in which WBMRI adds value, as part of a comprehensive surveillance protocol, continues to evolve in response to new evidence, growing experience, and more widespread adoption. In July 2023, the AACR reconvened an international, multidisciplinary panel to revise and update recommendations stemming from the 2016 AACR Special Workshop on Childhood Cancer Predisposition. That initial meeting resulted in a series of publications in Clinical Cancer Research in 2017, including "Pediatric Cancer Predisposition Imaging: Focus on Whole-Body MRI." This 2024 review of WBMRI in cancer predisposition syndrome updates the 2017 WBMRI publication, the revised recommendations derived from the 2023 AACR Childhood Cancer Predisposition Workshop based on available data, societal guidelines, and expert opinion. Different aspects of acquiring and interpreting WBMRI, including diagnostic accuracy, are discussed. The application of WBMRI in resource-poor environments, as well as integration of whole-body imaging techniques with emerging technologies, such as cell-free DNA ("liquid biopsies") and artificial intelligence/machine learning, is also considered., (©2024 American Association for Cancer Research.)

Genomic instability disorders are characterized by DNA or chromosomal instability, resulting in various clinical manifestations, including developmental anomalies, immunodeficiency, and increased risk of developing cancers beginning in childhood. Many of these genomic instability disorders also present with exquisite sensitivity to anticancer treatments such as ionizing radiation and chemotherapy, which may further increase the risk of second cancers. In July 2023, the American Association for Cancer Research held the second Childhood Cancer Predisposition Workshop, where multidisciplinary international experts discussed, reviewed, and updated recommendations for children with cancer predisposition syndromes. This article discusses childhood cancer risks and surveillance recommendations for the group of genomic instability disorders with predominantly recessive inheritance, including the DNA repair disorders ataxia telangiectasia, Nijmegen breakage syndrome, Fanconi anemia, xeroderma pigmentosum, Bloom syndrome, and Rothmund-Thomson syndrome, as well as the telomere biology disorders and mosaic variegated aneuploidy. Recognition of children with genomic instability disorders is important in order to make the proper diagnosis, enable genetic counseling, and inform cancer screening, cancer risk reduction, and choice of anticancer therapy., (©2024 American Association for Cancer Research.)

Objective Esophageal cancer is a gastrointestinal cancer with a poor prognosis. However, it is curable and can be treated endoscopically if it is detected at an early stage. The objective of this study was to identify the factors that contribute to early detection. Methods From April 2011 to December 2019, we retrospectively investigated consecutive patients diagnosed with esophageal squamous cell carcinoma (ESCC) through upper gastrointestinal endoscopy at two hospitals of Kawasaki Medical University based on medical records. The factors contributing to the early detection of ESCC were investigated by comparing patients with ESCC with those undergoing health checkups in whom no organic lesions were found in the upper gastrointestinal tract on endoscopy (controls). Patients Factors contributing to early detection were examined in 402 ESCC cases and 391 sex- and age-matched controls, and early and advanced cancers were compared along with the risk factors for ESCC. Results A multivariate analysis showed that alcohol consumption and smoking, concomitant cancer of other organs, and a low body mass index (BMI) were factors associated with ESCC (odds ratio [OR], 4.65; 95% confidence interval [CI], 2.880-7.520, OR, 3.63; 95% CI, 2.380-5.540, OR, 2.09; 95% CI, 1.330-3.270, OR, 6.38; 95% CI, 3.780-10.800), whereas dyslipidemia was significantly less common in patients with ESCC (OR, 0.545; 95% CI, 0.348-0.853). Comparing early and advanced cancers, a history of endoscopic screening was the only factor involved in early detection (OR, 7.93; 95% CI, 4.480-14.000). Conclusion The factors associated with ESCC include alcohol consumption, smoking, concomitant cancer of other organs, and a low BMI. Endoscopy in subjects with these factors may therefore be recommended for the early detection of ESCC.

To evaluate different Lynch syndrome (LS) screening approaches and establish an efficient and sensitive strategy are critical for clinical practice. In total, 583 patients with colorectal carcinoma (CRC) at Fudan University Shanghai Cancer Center were enrolled. Patient samples were examined by immunohistochemistry (IHC) and next-generation sequencing (NGS), and MLH1 promoter hypermethylation (MPH) was detected in MLH1-deficient cases. Germline genetic testing was performed in cases with deleterious variants and large genomic rearrangements (LGRs) of tumor MMR genes were detected in cases with dMMR or MSI-H cases with no MMR germline variants. Our results showed that triage with IHC and followed by BRAF/MLH1 methylation testing (Strategy 1) identified 93.3% (70/75) of LS cases. IHC followed by germline NGS (Strategy 2) or direct tumor NGS (Strategy 3) both identified 98.7% (74/75) of LS cases. The proportion of LGRs in LS cases was 16.0% (12/75), while 84.0% (63/75) showed SNV/Indel. The average cost per patient was ¥6010.81, ¥6058.48, and ¥8029.98 for Strategy 1, Strategy 2 and Strategy 3, respectively. The average time spent on different strategies was 4.74 days (Strategy 1), 4.89 days (Strategy 2), and 14.50 days (Strategy 3) per patient, respectively. LS and Lynch-like syndrome (LLS) were associated with an earlier onset age than MPH. In conclusion, we compared different workflows for LS screening and IHC plus germline NGS is recommended for LS screening when taking sensitivity, time, and cost into account. Moreover, multiplex ligation-dependent probe amplification made up for the shortcoming of NGS and should be incorporated into routine screening., (© 2024 The Author(s). International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Introduction: Early detection of colorectal cancer (CRC) and clinically relevant (advanced) adenomas leads to a significant reduction of CRC-related mortality and morbidity. However, the faecal immunochemical test (FIT) suffers from a high number of false-positive results and is insensitive to detecting advanced adenomas, resulting in false-negative results for these premalignant lesions. Therefore, more accurate, non-invasive screening tools are needed for the detection and prognostication of colorectal neoplasia. Previous research on volatile organic compounds (VOCs) analysis in breath and faeces has shown to be promising potential biomarkers for this purpose. Several VOC-sampling methods, including breath sampling, have improved significantly over the recent years resulting in an increased reliability of measurements. Therefore, we aim to identify relevant VOC profiles in exhaled breath and faeces for the diagnosis of colorectal neoplasia while taking into account relevant confounding factors. Follow-up data will be used to identify relevant VOC profiles in exhaled breath and faeces for the prognostication of colorectal neoplasia. Finally, a biobank will be set up for future research questions on this topic., Methods and Analysis: Subjects with positive FIT within the Dutch national CRC cancer screening programme are included. Subjects are asked to fill in questionnaires and exhaled breath, faeces and blood are sampled prior to colonoscopy. All subjects are asked to fill in follow-up questionnaires at years 1 and 5 of the study. In case of surveillance colonoscopies, subjects are asked to provide exhaled breath, faeces and blood prior to the colonoscopy again. Breath sampling is performed using the ReCIVA breath sampler. VOCs in breath and faeces are analysed using gas-chromatography-mass spectrometry (GC-MS). Raw GC-MS data is preprocessed and analysed using machine learning techniques., Ethics and Dissemination: The study is approved by the medical ethics committee at the Maastricht University Medical Center (NL74844.068.20) in November 2021 and started inclusion in January 2022., Competing Interests: Competing interests: Part of the work of DJ, outside the submitted work, has been financed by public private partnership grants of the Dutch Top Knowledge Institute (TKI) Agri&Food and Health Holland, by the Carbokinetics program as part of the NWO-CCC Partnership Program, by Organic A2B/Mothersfinest BV, and by EU/FP7 SysmedIBD/305563, BIOM/305479, Character/305676 and H2020 DisCOvERIE/848228. AS is assistant professor at Maastricht University and is an advisor at Owlstone Medical (Cambridge, UK), a breath-based medical company aiming for the non-invasive detection of diseases. ZM reports grants from MLDS, Niels Stensen Fellowship, ZonMw and Galapagos and has served as a speaker for Galapagos and as an advisor for Johnson & Johnson and Pfizer. ES, AM, FJvS, RvV and HRC declare no conflicts of interests., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Participant management in a lung cancer screening (LCS) depends on the assigned Lung Imaging Reporting and Data System (Lung-RADS) category, which is based on reliable detection and measurement of pulmonary nodules. The aim of this study was to compare the agreement of two AI-based software tools for detection, quantification and categorization of pulmonary nodules in an LCS program in Northern Germany (HANSE-trial). 946 low-dose baseline CT-examinations were analyzed by two AI software tools regarding lung nodule detection, quantification and categorization and compared to the final radiologist read. The relationship between detected nodule volumes by both software tools was assessed by Pearson correlation (r) and tested for significance using Wilcoxon signed-rank test. The consistency of Lung-RADS classifications between Software tool 1 (S1, Aview v2.5, Coreline Soft, Seoul, Korea) and Software tool 2 (S2, Prototype ''ChestCTExplore'', software version ToDo, Siemens Healthineers, Forchheim, Germany) was evaluated by Cohen's kappa (κ) and percentual agreement (PA).The derived volumes of true positive nodules were strongly correlated (r > 0.95), the volume derived by S2 was significantly higher than by S1 (P < 0.0001, mean difference: 6mm 3 ). Moderate PA (62%) between S1 and S2 was found in the assignment of Lung-RADS classification (κ = 0.45). The PA of Lung-RADS classification to final read was 75% and 55% for S1 and S2, but the incorporation of S1 into the initial nodule detection and segmentation must be considered here. Significant nodule volume differences between AI software tools lead to different Lung-RADS scores in 38% of cases, which may result in altered participant management. Therefore, high performance and agreement of accredited AI software tools are necessary for a future national LCS program., Competing Interests: Declarations Competing interests This work was supported by Siemens Healthcare GmbH. Jonathan Sperl is an employee of Siemens Healthcare GmbH, Erlangen, Germany. For the remaining authors none were declared., (© 2024. The Author(s).)

The sensitivity of currently available screening tools for urothelial carcinoma (UC) remains unsatisfactory particularly at early stages. Hence, we aimed to establish a novel blood-based screening tool for urothelial carcinoma. We measured serum d-amino acid levels in 108 and 192 patients with and without UC individuals in the derivation cohort, and 15 and 25 patients with and without UC in the validation cohort. Serum d-asparagine levels were significantly higher in patients with UC than in those without UC (p < 0.0001). We developed a novel screening equation for the diagnosis of urothelial carcinoma using d-asparagine in serum and estimated the glomerular filtration rate (eGFR). Serum d-asparagine levels adjusted for eGFR exhibited high performance in the diagnosis of UC (AUC-ROC, 0.869; sensitivity, 80.6 %; specificity, 82.7 %), even in early-stage UC (AUC-ROC: 0.859, sensitivity: 83.3 %, specificity: 82.3 %), which were previously misdiagnosed via urinary occult blood or urine cytology. This established strategy combined with urinary occult blood, improves diagnostic ability (sensitivity: 93.7 %, specificity: 70.1 %)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Atypical squamous cells of undetermined significance (ASC-US) often present diagnostic challenges with cytology-based results, leading to potential underdiagnosis or overdiagnosis. An effective triage method is essential for managing these cases to reduce unnecessary referrals and treatment., Methods: A total of 322 women diagnosed with ASC-US were tested for HPV-DNA and the PAX1 and JAM3 methylation (PAX1 m /JAM3 m ) test in the study., Results: Methylation levels of PAX1 and JAM3 were significantly elevated in cervical lesions classified as CIN2 or more severe lesions (CIN2+). The methylation assay demonstrated a sensitivity of 83.8% and a specificity of 95.8%, outperforming HPV-DNA testing in differentiating high-grade cervical lesions among women with ASC-US. Moreover, PAX1 m /JAM3 m testing significantly reduced the colposcopy referral rate for further diagnostic procedures in high-risk HPV-positive women by 79.5%., Conclusions: PAX1 m /JAM3 m testing shows promise as a reliable supplemental method to HPV-DNA testing for the triage of women with cytologic ASC-US. In addition, the molecular triage based on the CISCER assay or single PAX1 or JAM3 methylation, had better effects in the women with non-HPV16/18 group. This approach could potentially minimize overtreatment and unnecessary referrals in clinical practice, enhancing patient management and resource utilization., Competing Interests: Declarations Ethical approval The name of the Approval Committee or the Internal Review Board (IRB). This research has been approved by the Ethics Committee of Zhejiang Provincial People’s Hospital. Human Ethics and Consent to participate declarations All participants have provided written informed consents according to the Declaration of Helsinki, and which have been approved by the Ethics Committee of Zhejiang Provincial People’s Hospital (No.2021SJ020). Consent for publication Not applicable. Clinical trial number Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

The absolute number of annual cases of gastric cancer in Europe is rising. The Council of the European Union has recommended implementation of gastric cancer screening for countries or regions with a high gastric cancer incidence and death rates. However, as of 2024 no organised gastric cancer screening programme has been launched in Europe.There are several ways to decrease gastric cancer burden, but the screen and treat strategy for Helicobacter pylori (H. pylori ) seems to be the most appropriate for Europe. It has to be noted that increased use of antibiotics would be associated with this strategy.Only organised population-based cancer screening is recommended in the European Union, therefore gastric cancer screening also is expected to fulfil the criteria of an organised screening programme. In this respect, several aspects of screening organisation need to be considered before full implementation of gastric cancer prevention in Europe; the age range of the target group, test types, H. pylori eradication regimens and surveillance strategies are among them. Currently, ongoing projects (GISTAR, EUROHELICAN, TOGAS and EUCanScreen) are expected to provide the missing evidence. Feedback from the decision-makers and the potential target groups, including vulnerable populations, will be important to planning the programme.This paper provides an overview of the recent decisions of the European authorities, the progress towards gastric cancer implementation in Europe and expected challenges. Finally, a potential algorithm for gastric cancer screening in Europe is proposed., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Hepatocellular carcinoma (HCC) is plagued by failures across the cancer care continuum, leading to frequent late-stage diagnoses and high mortality. We evaluated the effectiveness of mailed outreach invitations plus patient navigation to promote HCC screening process completion in patients with cirrhosis., Methods: Between April 2018 and September 2021, we conducted a multicentre pragmatic randomised clinical trial comparing mailed outreach plus patient navigation for HCC screening (n=1436) versus usual care with visit-based screening (n=1436) among patients with cirrhosis at three US health systems. Our primary outcome was screening process completion over a 36-month period, and our secondary outcome was the proportion of time covered (PTC) by screening. All patients were included in intention-to-screen analyses., Results: All 2872 participants (median age 61.3 years; 32.3% women) were included in intention-to-screen analyses. Screening process completion was observed in 6.6% (95% CI: 5.3% to 7.9%) of patients randomised to outreach and 3.3% (95% CI: 2.4% to 4.3%) of those randomised to usual care (OR 2.05, 95% CI: 1.44 to 2.92). The intervention increased HCC screening process completion across most subgroups including age, sex, race and ethnicity, Child-Turcotte-Pugh class and health system. PTC was also significantly higher in the outreach arm than usual care (mean 37.5% vs 28.2%; RR 1.33, 95% CI: 1.31 to 1.35). Despite screening underuse, most HCC in both arms were detected at an early stage., Conclusion: Mailed outreach plus navigation significantly increased HCC screening process completion versus usual care in patients with cirrhosis, with a consistent effect across most examined subgroups. However, screening completion remained suboptimal in both arms, underscoring a need for more intensive interventions., Trial Registration Number: NCT02582918., Competing Interests: Competing interests: AGS has served as a consultant or on advisory boards for Bayer, FujiFilm Medical Sciences, Exact Sciences, Universal Dx, Glycotest, Roche, Freenome, DELFI, GRAIL, Genentech, AstraZeneca, Eisai, Exelixis, Merck, Boston Scientific, Sirtex and HistoSonics. CM has served as a consultant for Freenome. None of the other authors have any relevant conflicts of interest to disclose., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Contrast-enhanced mammography (CEM) and magnetic resonance imaging (MRI) have shown similar diagnostic performance in detection of breast cancer. Limited CEM data are available for high-risk breast cancer screening. The purpose of the study was to prospectively investigate the efficacy of supplemental screening CEM in elevated risk patients., Materials and Methods: A prospective, single-institution, institutional review board-approved observational study was conducted in asymptomatic elevated risk women age 35 years or older who had a negative conventional two-dimensional digital breast tomosynthesis screening mammography (MG) and no additional supplemental screening within the prior 12 months., Results: Four hundred sixty women were enrolled from February 2019 to April 2021. The median age was 56.8 (range, 35.0-79.2) years; 408 of 460 (88.7%) were mammographically dense. Biopsy revealed benign changes in 22 women (22/37, 59%), high-risk lesions in four women (4/37, 11%), and breast cancer in 11 women (11/37, 30%). Fourteen cancers (10 invasive, tumor size range 4-15 mm, median 9 mm) were diagnosed in 11 women. The overall supplemental cancer detection rate was 23.9 per 1,000 patients, 95% CI (12.0 to 42.4). All cancers were grade 1 or 2, ER+ ERBB2-, and node negative. CEM imaging screening offered high specificity (0.875 [95% CI, 0.844 to 0.906]), high NPV (0.998 [95% CI, 0.993 to 1.000), moderate PPV1 (0.164 [95% CI, 0.076 to 0.253), moderate PPV3 (0.275 [95% CI, 0.137 to 0.413]), and high sensitivity (0.917 [95% CI, 0.760 to 1.000]). At least 1 year of imaging follow-up was available on all patients, and one interval cancer was detected on breast MRI 4 months after negative screening CEM., Conclusion: A pilot trial demonstrates a supplemental cancer detection rate of 23.9 per 1,000 in women at an elevated risk for breast cancer. Larger, multi-institutional, multiyear CEM trials in patients at elevated risk are needed for validation.

The incidence of Early-Onset Colorectal Cancer (EOCRC) is increasing. However, the prognosis of EOCRC compared to Late-Onset Colorectal Cancer (LOCRC), and the ideal age for initial colorectal cancer (CRC) screening are not clear. In this study, we identified the pathological differences between the groups and determined the optimal screening age for CRC patients. We included 10,172 patients diagnosed with CRC from January 2011 to December 2021 in this study. Survival differences were compared by plotting Kaplan-Meier survival curves and conducting landmark analysis. Additionally, the diagnostic age of CRC patients was analyzed using age cumulative curves. Compared to LOCRC patients, EOCRC patients had a higher proportion of deficient mismatch repair (dMMR) and more advanced TNM staging (P < 0.05). The five-year survival of EOCRC patients was significantly better than that of LOCRC patients (P < 0.05). Laparoscopic surgery improved the long-term survival of EOCRC patients. Proficient mismatch repair (pMMR) favored the long-term survival of EOCRC patients. The survival rate of EOCRC patients at TNM stages I and II was higher than that of LOCRC patients at the same stages (P < 0.05). The age cumulative curve showed a substantial increase in the number of CRC patients at 40 years. The long-term prognosis of EOCRC patients is better than that of LOCRC patients, especially among those with pMMR, stages I-II, and who undergo laparoscopic surgery. For people with a high risk of cancer, such as a family history of cancer and poor lifestyle habits, the starting age for CRC screening should be 40 years., (© 2024. The Author(s).)

Objective: Gastric cancer ranks as one of the top five deadliest cancers worldwide and is often diagnosed at late stages. Analysis of saliva may provide a non-invasive approach for detection of malignancies in organs associated with the oral cavity. This research aims to analyze salivary microRNA expression together with clinical and demographic features with the aim of diagnosing gastric cancer., Materials: The study included 19 patients with early-stage gastric cancer and 19 healthy controls. Saliva samples were collected and processed for RNA isolation. Salivary expression of miR-223-3p and miR-21-5p were measured using quantitative reverse-transcription polymerase chain reaction (RT-qPCR). Receiver operating characteristic (ROC) curves were generated to evaluate the accuracy of diagnostic models. Machine learning algorithms, multiple logistic regression, and principal component analysis (PCA) were used to assess the predictive power of miRNAs in conjunction with clinical-demographic features., Results: Significant upregulation of miR-223-3p and downregulation of miR-21-5p in saliva were observed in patients with gastric cancer. The area under ROC curve (AUC) values for salivary miR-21-5p, salivary miR-223-3p, and their multiple logistic regression were determined to be 0.723, 0.791, and 0.850, respectively. The AUC for multiple logistic regression model was 0.919. The PCA model led to the highest diagnostic odds ratio (DOR) of 134.33 (sensitivity = 0.785, specificity = 1.00, AUC = 903). Application of machine learning methods, and in particular a random forest algorithm, showed high accuracy in diagnosing patients with gastric cancer (sensitivity = 1.00, specificity = 0.857, AUC = 0.93)., Conclusion: The application of validated salivary diagnostics in clinical practice could help facilitate earlier diagnosis of gastric cancer and improve medical outcome. Expression of miR-21 and miR-223-3p in saliva together with clinical and demographic features, appears promising in screening for GC., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Accessible mammography datasets and innovative machine learning techniques are at the forefront of computer-aided breast cancer diagnosis. However, the opacity surrounding private datasets and the unclear methodology behind the selection of subset images from publicly available databases for model training and testing, coupled with the arbitrary incompleteness or inaccessibility of code, markedly intensifies the obstacles in replicating and validating the model's efficacy. These challenges, in turn, erect barriers for subsequent researchers striving to learn and advance this field. To address these limitations, we provide a pilot codebase covering the entire process from image preprocessing to model development and evaluation pipeline, utilizing the publicly available Curated Breast Imaging Subset of Digital Database for Screening Mammography (CBIS-DDSM) mass subset, including both full images and regions of interests (ROIs). We have identified that increasing the input size could improve the detection accuracy of malignant cases within each set of models. Collectively, our efforts hold promise in accelerating global software development for breast cancer diagnosis by leveraging our codebase and structure, while also integrating other advancements in the field., (© 2024. The Author(s).)

We aimed to evaluate the diagnostic value of TruScreen, a real-time diagnostic technology, for cervical lesions in patients with different transformation zone (TZ) types. A total of 1908 women aged 34.0 ± 7.3 years who have received cytology, human papillomavirus (HPV) testing, TruScreen, and colposcopy were recruited. The clinical performances of these tests were evaluated for their detection of high-grade squamous intraepithelial lesion (HSIL), adenocarcinoma in situ (AIS), or more severe lesions in patients with different TZ types. For the detection of HSIL, AIS, or more severe lesions, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of TruScreen were 65.08%, 64.76%,11.55%, and 96.33%, respectively, which were similar to cytology (all P values > 0.05). For the detection of HSIL + in patients with type 3 TZ, the sensitivity, specificity, PPV, and NPV of TruScreen were 72.29%, 67.59%, 13.86%, and 97.13%, respectively, which were significantly higher than the sensitivity (51.16%, P = 0.029), specificity (59.59%, P = 0.001), PPV (7.94%, P = 0.016), and NPV (94.71%, P = 0.049) in type 1 and type 2 TZs. TruScreen has detection accuracy comparable to cytology and performs even better in patients with type 3 TZ., (© 2024. The Author(s).)

Background: The World Health Organization has set ambitious goals to eliminate cervical cancer, necessitating evidence on increasing coverage and access to screening and treatment in high-burden areas. We implemented a pilot program to assess the feasibility of obtaining self-collected specimens for high-risk human papillomavirus (hr-HPV) testing in Nzulezo stilt village, a hard-to-reach community in Ghana, and inviting only hr-HPV-positive women to a central location for colposcopy and possible treatment. Subsequently, this study aimed to investigate the prevalence of hr-HPV infection and cervical lesions among the women and to explore factors potentially associated with hr-HPV infection among them., Methods: This pilot community-based cross-sectional study utilized data from screening sessions held from 2 to 20 November 2021 with specimens collected by participants using Evalyn brushes. HPV DNA testing was performed using the Sansure MA-6000 platform, while visual inspection utilized the Enhanced Visual Assessment (EVA) mobile colposcope. Univariate and multivariable nominal logistic regression was employed to explore factors associated with hr-HPV positivity., Results: Among 100 women screened (mean age, 43.6 ± 14.5 years), the overall hr-HPV prevalence rate was 39.0% (95% CI, 29.4-49.3). The prevalence rates of hr-HPV genotypes were stratified as follows: HPV16-8.0% (95% CI, 3.5-15.2), HPV18-5.0% (95% CI, 1.6-11.2), and other genotype(s) - 31.0% (95% CI, 22.1-41.0). Single-genotype infections with HPV16 and HPV18 were found in 4.0% (95% CI, 1.1-9.9) and 3.0% (95% CI, 0.6-8.5) of women, respectively. Mixed infections were observed in 1.0% (95% CI, 0.0-5.4) for HPV16 + 18, 3.0% (95% CI, 0.6-8.5) for HPV16 + other type(s), and 1.0% (95% CI, 0.0-5.4) for HPV18 + other type(s). The prevalence of cervical lesions among hr-HPV-positive women screened via colposcopy was 11.4% (95% CI, 3.2-26.7). In the multivariable model, reliance on other sources for medical bill payment was associated with hr-HPV infection (aOR, 0.20; 95% CI, 0.04-0.93), whereas age was not (aOR, 1.02; 95% CI, 0.99-1.05)., Conclusions: A high hr-HPV infection prevalence was recorded among the women. Utilizing technologies such as self-sampling, HPV DNA testing, and mobile colposcopy enables screening and treatment in remote and hard-to-reach communities where access to cervical cancer screening and treatment would otherwise be limited. Further research is warranted to assess the value and scalability of this approach in similar remote areas and its potential implementation in future programs., (© 2024. The Author(s).)

Endometrial cancer (EC) rates are continuing to rise and it remains the most common gynecologic cancer in the US. Existing diagnostic methods are invasive and can cause pain and anxiety. Hence, there is a need for less invasive diagnostics for early EC detection. The study objective was to evaluate the utility of growth factors collected through minimally invasive cervicovaginal lavage (CVL) sampling as diagnostic and prognostic biomarkers for EC. CVL samples from 192 individuals undergoing hysterectomy for benign or malignant conditions were collected and used to quantify the concentrations of 19 growth and angiogenic factors using multiplex immunoassays. Patients were categorized based on disease groups: benign conditions (n = 108), endometrial hyperplasia (n = 18), and EC (n = 66). EC group was stratified into grade 1/2 endometrial endometrioid cancer (n = 53) and other EC subtypes (n = 13). Statistical associations were assessed using receiver operating characteristics, Spearman correlations and hierarchical clustering. Growth and angiogenic factors: angiopoietin-2, endoglin, fibroblast activation protein (FAP), melanoma inhibitory activity, and vascular endothelial growth factor-A (VEGF-A) were significantly (p < 0.0001) elevated in EC patients. A multivariate model combining 11 proteins with patient age and body mass index exhibited excellent discriminatory potential (area under curve = 0.918) for EC, with a specificity of 90.7% and a sensitivity of 87.8%. Moreover, angiopoietin-2, FAP and VEGF-A significantly (p < 0.05-0.001) associated with tumor grade, size, myometrial invasion, and mismatch repair status. Our results highlight the innovative use of growth and angiogenic factors collected through CVL sampling for the detecting endometrial cancer, showcasing not only their diagnostic potential but also their prognostic value., (© 2024. The Author(s).)

Introduction: Identifying cancer earlier can help save lives. An increasingly popular approach to diagnosing cancer earlier is in the development of risk prediction models to be applied to the electronic healthcare record of patients. Development of these models requires systematic and thorough identification of the risk factors that might increase an individual's propensity to develop the disease. This protocol sets out the methods for an umbrella review to identify risk factors that might be included in these models. The example used is pancreatic cancer, a disease with a high percentage of late-stage diagnoses and consequent high mortality., Methods and Analysis: Relevant systematic reviews will be identified through searching of MEDLINE and EMBASE via Ovid and the Science Citation Index Expanded of the Web of Science Core Collection. Screening will be performed by two independent reviewers using Covidence software and the results reported as a Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagram. Data from eligible studies will be extracted independently by two reviewers and each systematic review will be graded using defined credibility assessment criteria and the ROBIS (Risk of Bias in Systematic Reviews) tool. Results will be presented in detail for each paper. Summary results for each risk factor will be discussed in the narrative and summarised using a table, graphical summary and an infographic., Ethics and Dissemination: Ethical approval is not required for this review. Results of the review will be disseminated by publication in a peer-reviewed journal and presented at conferences., Prospero Registration Number: CRD42024526338., Competing Interests: Competing interests: FMW is a member of the BMJ Open Editorial Board., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background: The purpose of the Accelerating Colorectal Cancer Screening and Follow-up through Implementation Science (ACCSIS) Program, a Cancer Moonshot℠ Initiative, is to support research to build the evidence base on multilevel interventions that increase rates of colorectal cancer screening, follow-up, and referral to care to address disparities in colorectal cancer screening. The National Cancer Institute funded eight Research Projects to implement multilevel interventions to improve colorectal cancer screening among communities who traditionally have been medically underserved. To analyze the impact of ACCSIS across Research Projects, the consortium developed a set of common data elements. The purpose of this paper is to describe the process of developing the common data elements to facilitate analysis of ACCSIS data as well as support and inform implementation science research studies., Methods: The ACCSIS Data, Design, and Analysis Work Group was tasked with designing common data elements through a review of existing data collection instruments, examination of data elements proposed by the ACCSIS Research Projects, and deliberations on the data required to compare across the Research Projects. ACCSIS Consortium members drafted, revised, and finalized a common data elements document consisting of variables to collect and surveys to administer to evaluate ACCSIS implementation activities and outcomes in a standardized manner across the Research Projects., Results: The ACCSIS Consortium decided to collect the following categories of common data elements: characteristics across multiple levels of the multicomponent interventions, implementation climate, and determinants; interventions and strategies; implementation outcome constructs and definitions; colorectal cancer screening episodes (screening, diagnostic testing follow-up, cancer detection, and cancer treatment); and cost measures. To assess implementation climate, the consortium prioritized constructs from five domains of the Consolidated Framework for Implementation Research., Conclusions: The ACCSIS common data elements offer a set of harmonization data for future implementation efforts. The consortium is conducting a systematic assessment using both quantitative and qualitative approaches to assess data quality and approaches to improve and sustain data collection. Lessons learned from these ongoing activities will offer additional insights to tailor the ACCSIS common data elements and support efforts to increase colorectal cancer screening for populations experiencing disparities., (© 2024. The Author(s).)

The Prostate Specific Antigen (PSA) blood test is still the only screening tool for prostate cancer. It is recommended between the ages of 50 and 69 as part of a shared decision making process between a patient and his or her doctor using a decision aid, as the test carries a significant risk of overdiagnosis. If a patient wishes to be screened, either because he is at higher risk, or because he places greater importance on a modest reduction in cancer-related mortality, the frequency of screening depends on his age, family history, and whether he is part of a high-risk group. The use of multiparametric MRI after a positive PSA result can reduce the number of biopsies and, consequently, the risk of overdiagnosis., Competing Interests: Marie-Anne Durand a développé l’outil d’aide à la décision pour la décision médicale partagée « Option Grid »”, qui est sous licence auprès de la compagnie EBSCO Health. Elle est consultante pour EBSCO Health et reçoit des redevances. Les autres auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Early detection and treatment of skin cancer are important for patient recovery and survival. Dermoscopy images can help clinicians for timely identification of cancer, but manual diagnosis is time-consuming, costly, and prone to human error. To conduct this, an innovative deep learning-based approach has been proposed for automatic melanoma detection. The proposed method involves preprocessing dermoscopy images to remove artifacts, enhance contrast, and cancel noise, followed by feeding them into an optimized Convolutional Neural Network (CNN). The CNN is trained using an innovative metaheuristic called the Improved Chameleon Swarm Algorithm (CSA) to optimize its performance. The approach has been validated using the SIIM-ISIC Melanoma dataset and the results have been confirmed through rigorous evaluation metrics. Simulation results demonstrate the efficacy of the proposed method in accurately diagnosing melanoma from dermoscopy images by highlighting its potential as a valuable tool for clinicians in early cancer detection., (© 2024. The Author(s).)

Objective: To evaluate the cost-effectiveness of risk-stratified hepatocellular carcinoma (HCC) screening in diabetic patients with metabolic dysfunction-associated steatotic liver disease (MASLD)., Design: A state-transition model from a healthcare payer perspective on a lifetime horizon., Setting: Japan., Population: A hypothetical cohort of 50-year-old diabetic patients with MASLD risk-stratified according to degree of obesity and progression to cirrhosis. Metabolic dysfunction-associated steatotic liver (MASL), metabolic dysfunction-associated steatohepatitis (MASH) and MASH cirrhosis are progressive manifestations of this specific type of liver disease., Intervention: Abdominal ultrasound (US), US with alpha-fetoprotein (AFP), US with AFP and lectin-reactive alpha-fetoprotein (AFP-L3), CT, extracellular contrast-media-enhanced MRI (ECCM-MRI), gadoxetic acid-enhanced MRI (EOB-MRI) and no screening., Main Outcome Measure: Costs, quality-adjusted life-years (QALYs), incremental cost-effectiveness ratios (ICERs), early-stage HCC cases, advanced-stage HCC cases and HCC-related deaths., Results: EOB-MRI is the most cost-effective screening method for non-obese diabetic patients with MASH cirrhosis and for obese diabetic patients with MASH and MASH cirrhosis. Cost-effectiveness was sensitive to HCC incidence in non-obese diabetic patients with MASH cirrhosis and obese diabetic patients with MASH, and the adherence rate of HCC screening in obese diabetic patients with MASH. When the semiannual HCC incidence was between 0.008 and 0.0138 in non-obese diabetic patients with MASH cirrhosis, US with AFP was more cost-effective than EOB-MRI. Cost-effectiveness acceptability curves showed that EOB-MRI was 50.7%, 96.0% and 99.9% cost-effective in obese diabetic patients with MASH and non-obese diabetic patients with MASH cirrhosis, and obese diabetic patients with MASH cirrhosis at a willingness-to-pay level of $50 000 per QALY gained. Compared with no screening in 100 000 non-obese diabetic patients with MASH cirrhosis and obese diabetic patients with MASH cirrhosis, EOB-MRI reduced total costs by US$69 million and by US$142 million, increased lifetime effectiveness by 12 546 QALYs and by 15 815 QALYs, detected 17 873 and 21 014 early-stage HCC cases, and averted 2068 and 2471 HCC-related deaths, respectively., Conclusions: Of all HCC screening methods for diabetic patients with MASH cirrhosis, EOB-MRI yields the greatest cost-saving with the highest QALYs, detects the greatest number of early-stage HCC cases and averts the greatest number of advanced-stage HCC cases and HCC-related deaths. The findings provide important insights for the precise implementation of risk-stratified HCC surveillance to reduce morbidity and mortality and improve the quality of life in diabetic patients with MASLD., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Cervical cancer is the 2nd most common female cancer among Sri Lankan females and is almost associated with sexually transmitted cervicovaginal human papillomavirus (HPV) infection. The study objectives were to determine the prevalence of vaginal and cervical HPV infection among 35year old ever-married women and assess the validity of primary healthcare provider-collected vaginal HPV/DNA specimens as a cervical cancer screening tool to improve the coverage of the programme., Method: A descriptive cross-sectional study was carried out from the 1st of September 2018 to the 31st of January 2019. Ever-married women 35 years of age in Kalutara district were the study population. Two women from each Public Health Midwife area (n = 413) were selected randomly from the relevant area eligible families register/s. HPV/DNA cervical specimen and vaginal specimen collection (n = 621) were carried out. Specimens were screened by the Cobas 4800 HPV/DNA automated Polymerase Chain Reaction (PCR) machine. Participants' profiles were recorded by the research assistants using an interviewer-administered questionnaire., Results: The overall prevalence of vaginal and cervical HPV infection was 7.08% (95% CI; 5.2-9.4%) and 6.12% (95% CI; 4.26-8.3%) respectively. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), diagnostic accuracy, and the kappa coefficient of the vaginal HPV/DNA screening method vs. cervical HPV/DNA screening method were 100%, 98.9%, 86.4%, 100%, 99% and 0.92 respectively., Conclusions: Vaginal HPV/DNA specimen screening method can be used as a cervical cancer screening tool due to its high validity. Pilots of the feasibility should be set up before the regional or national rollout of vaginal sampling strategies., (© 2024. The Author(s).)

Background: This study investigated clinicopathological factors associated with the visibility of early gastric cancer and the efficacy of linked color imaging., Methods: Patients with early gastric cancer who underwent endoscopic treatment between April 2021 and July 2022 were enrolled. All cases underwent white light imaging and linked color imaging. Three experts evaluated lesion visibility using a visual analog scale. A mean score ≥3 on white light imaging was defined as "good visibility", and <3 as "poor visibility". We extracted patient information and endoscopic and pathological data for the lesion and background mucosa, analyzed factors associated with the visibility of early gastric cancer, and compared visibility between white light imaging and linked color imaging., Results: Ninety-seven lesions were analyzed, with good visibility in 49 and poor visibility in 48. Multivariate analysis revealed small lesion size (odds ratio 1.89) and presence of endoscopic intestinal metaplasia (odds ratio 0.49) as significantly associated with the poor visibility of early gastric cancer. Mean visibility score was significantly higher for linked color imaging (P<0.001). Mean score for linked color imaging was significantly higher in the poor visibility group (P<0.001), but not significantly different in the good visibility group (P = 0.292). Mean score was significantly higher with linked color imaging in cases with endoscopic intestinal metaplasia (P = 0.0496) and lesions <20 mm in diameter (<10 mm, P = 0.002; 10-20 mm, P = 0.004)., Conclusions: Lesion size and endoscopic intestinal metaplasia are associated with the visibility of early gastric cancer in white light imaging. Linked color imaging improves visibility of gastric cancer with these factors., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Fukuda et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: Our objective was to compare the efficacy of digital breast tomosynthesis (DBT) and digital mammography (DM) in breast cancer screening and their impact on long-term overall survival (OS)., Methods: The study involved 48 549 consecutive mammography examinations between 2011 and 2015 at a medical center in Taiwan, identifying 545 women who were screened and diagnosed with breast cancer. Digital mammography and DBT examinations were alternated on different days. Patients were categorized based on mammographic modality, breast density, and American Joint Committee on Cancer (AJCC) stage. To determine the long-term outcome until August 2021, survival rates were analyzed using the Kaplan-Meier (K-M) survival analysis., Results: The mean age at breast cancer diagnosis was 53.2 years. Digital breast tomosynthesis examinations were significantly associated with early breast cancer (AJCC stage 0 to 2) (P = .022). The 5- and 9-year OS rates for all patients were 96.8% and 93.0%, respectively. The 5- and 9-year OS was significantly greater in the DBT group (98.4% and 96.8%) compared with the DM group (95.0% and 90.4%) (P = .030 for all). The K-M survival analysis demonstrated a significantly higher OS in the DBT group than the DM group (P = .037). Furthermore, DBT significantly improved OS in a cohort of women with stage II and III cancer (P = .032) and heterogeneously dense breasts (P = .045)., Conclusion: Screening with DBT is associated with early breast cancer diagnosis and higher survival rates compared with DM., (© Society of Breast Imaging 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

In evidence-based medicine frameworks, the highest level of evidence is derived from quantitative synthesis of double-masked, high-quality, randomly assigned controlled trials. Meta-analyses of randomly assigned controlled trials have demonstrated that screening mammography reduces breast cancer deaths. In the United States, every major guideline-producing organization has recommended screening mammography in average-risk women; however, there are controversies about age and frequency. Carefully controlled observational research studies and statistical modeling studies can address evidence gaps and inform evidence-based, contemporary screening practices. As breast imaging radiologists develop and evaluate existing and new screening tests and technologies, they will need to understand the key methodological considerations and scientific criteria used by policy makers and health service researchers to support dissemination and implementation of evidence-based screening tests. The Wilson and Jungner principles and the U.S. Preventive Services Task Force general analytic framework provide structured evaluations of the effectiveness of screening tests. Key considerations in both frameworks include public health significance, natural history of disease, cost-effectiveness, and characteristics of screening tests and treatments. Rigorous evaluation of screening tests using analytic frameworks can maximize the benefits of screening tests while reducing potential harms. The purpose of this article is to review key methodological considerations and analytic frameworks used to evaluate screening studies and develop evidence-based recommendations., (© Society of Breast Imaging 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Breast cancer remains a major public health concern, and early detection is crucial for improving survival rates. Metabolomics offers the potential to develop non-invasive screening and diagnostic tools based on metabolic biomarkers. However, the inherent complexity of metabolomic datasets and the high dimensionality of biomarkers complicates the identification of diagnostically relevant features, with multiple studies demonstrating limited consensus on the specific metabolites involved. Unlike previous studies that rely on singular feature selection techniques such as Partial Least Square (PLS) or LASSO regression, this research combines supervised and unsupervised machine learning methods with random sampling strategies, offering a more robust and interpretable approach to feature selection. This study aimed to identify a parsimonious and robust set of biomarkers for breast cancer diagnosis using metabolomics data. Plasma samples from 185 breast cancer patients and 53 controls (from the Cooperative Human Tissue Network, USA) were analyzed. This study also overcomes the common issue of dataset imbalance by using propensity score matching (PSM), which ensures reliable comparisons between cancer and control groups. We employed Univariate Naïve Bayes, L2-regularized Support Vector Classifier (SVC), Principal Component Analysis (PCA), and feature engineering techniques to refine and select the most informative features. Our best-performing feature set comprised 11 biomarkers, including 9 metabolites (SM(OH) C22:2, SM C18:0, C0, C3OH, C14:2OH, C16:2OH, LysoPC a C18:1, PC aa C36:0 and Asparagine), a metabolite ratio (Kynurenine-to-Tryptophan), and 1 demographic variable (Age), achieving an area under the ROC curve (AUC) of 98%. These results demonstrate the potential for a robust, cost-effective, and non-invasive breast cancer screening and diagnostic tool, offering significant clinical value for early detection and personalized patient management.

Background: Primary screening for high-risk human papillomavirus (hrHPV) with cytological triage for women with non-16/18 hrHPV-positive status has become popular in China. However, cytology relies on the subjective judgment of pathologists, leading to inconsistent clinical performance., Methods: A total of 657 hrHPV-positive women aged 25-64 years were enrolled in this cross-sectional study. All participants underwent colposcopic biopsy after cytology triage, with cytology residual specimens undergoing DNA methylation testing. CIN2+ and CIN3+ sensitivity and specificity were compared between the different triage strategies (n=487): PAX1 methylation (PAX1 m ) , Glycophorin C methylation (GYPC m ), cytology, and combinations between them or with HPV16/18., Results: The area under the receiver operating characteristic curves (AUCs) for PAX1 m and GYPC m in detecting CIN2 or worse (CIN2+) were 0.867 (95% confidence interval [CI]: 0.796-0.937) and 0.873 (95% CI: 0.808-0.938), respectively. The sensitivities of PAX1 m and GYPC m were consistent with those of cytology for both CIN2+ and CIN3+ detection. The relative specificities of PAX1 m and GYPC m for CIN2+ detection compared to cytology were 2.83 (95% CI: 2.33-2.45) and 3.09 (95% CI: 2.40-3.98), respectively. The relative specificities of combining HPV 16/18 with PAX1 m and GYPC m for CIN2+ detection compared to cytology were 3.38 (95% CI: 2.96-3.86) and 3.67 (95% CI: 3.15-4.27), respectively. Compared to low levels of DNA methylation, high levels of PAX1 m and GYPC m resulted in odd ratios (ORs) of 57.66 (95% CI: 13.57-409.12, p < 0.001) and 23.87 (95% CI: 6.49-115.42, p < 0.001) for CIN3+, adjusted for HPV 16/18 and cytology results., Conclusions: PAX1 m and GYPC m demonstrated superior ability to identify cervical precancerous lesions and cervical cancer, with AUC values exceeding 0.85. For detecting CIN2+/CIN3+ in women with hrHPV-positive status, DNA methylation (combined with HPV 16/18) showed higher specificity than cytology (combined with HPV 16/18) and is a potential molecular biomarker for detecting cervical (pre)cancer., (© 2024. The Author(s).)

Background: Professional guidelines recommend HCC screening in at-risk patients using semi-annual ultrasound with or without alpha-fetoprotein (AFP); however, this strategy has limited effectiveness due to low adherence and sensitivity. Increasing data support the potential role of blood-based biomarker panels, which could improve both aspects. The biomarker panel GALAD, comprised of sex, age, and 3 blood biomarkers (AFP, AFP-L3, and des-carboxy prothrombin des-carboxy prothrombin), has shown high sensitivity and specificity in biomarker phase II (case-control) and phase III (retrospective cohort) validation studies. However, prospective validation in a large phase IV biomarker clinical utility trial is necessary before its adoption in practice., Methods: The National Liver Cancer Screening Trial is an adaptive pragmatic randomized phase IV trial, which began enrollment in January 2024, comparing ultrasound-based versus biomarker-based screening in 5500 patients with chronic hepatitis B infection or cirrhosis from any etiology. Eligible patients are randomly assigned in a 1:1 ratio to semi-annual screening with ultrasound ± alpha-fetoprotein (arm A) or semi-annual screening with GALAD (arm B). Randomization is stratified by enrollment site, liver disease severity (per Child-Pugh class), liver disease etiology (viral, nonviral, and noncirrhotic HBV), and sex. Patients are being recruited from 15 sites (a mix of tertiary care academic referral centers, safety-net health systems, and large community health systems) over a 3-year period, and the primary endpoint, reduction in late-stage HCC, will be assessed at the end of year 5.5., Discussion: The results of this trial will inform the best strategy for HCC screening and early-stage detection in patients with chronic liver diseases. If GALAD shows superiority, HCC screening would primarily shift from an ultrasound-based strategy to the adoption of the biomarker panel., Trial Registration: NCT06084234., Trial Status: The TRACER Study is actively enrolling., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Study of Liver Diseases.)

Background: Most women who are high-risk human papilloma virus (hrHPV) positive in a cervical cancer screening test will spontaneously heal from their infection. Visual inspection with acetic acid (VIA) is recommended by the World Health Organization as a triage test for cervical screening, however its accuracy as a triage test has been questioned. In this study, we aimed to examine the sensitivity and specificity of VIA with and without Lugol's iodine as a triage test to detect cervical intraepithelial neoplasia (CIN2+) among women who tested positive for hrHPV after self-sampling., Method: This two-armed randomized controlled trial (RCT) took place in Adama, Ethiopia. The women who tested positive for vaginal hrHPV (Anyplex ΙΙ, Seegene) after self-sampling were randomized to VIA with or without iodine and appointed to a midwife-led clinic. The result of the triage test was categorized as positive, negative, suspicion of cancer or inconclusive, and treated accordingly. Cervical biopsies were collected from women who were hrHPV positive to serve as a gold standard., Results: 22.4% (197/878) of women tested hrHPV positive. Sensitivity and specificity for VIA to detect CIN2+was 25.0% (95% CI 0.6 to 80.0) and 82.7% (95% CI 69.7 to 91.8), respectively. For VIA with iodine, the sensitivity was 50.0% (95% CI 0.7 to 93.2) and the specificity 86.3% (95% CI 71.4 to 93.0). The difference between the two methods was not statistically significant, p=0.5. The odds of detecting CIN2+ was 5.4 times higher if positive for VIA with iodine compared with a negative result. For VIA without iodine, the odds of detecting CIN2+ was 1.6 compared with a negative result. The odds of detecting CIN2+ was 6.4 times higher if the women were HIV positive than for those who were HIV negative., Conclusion: VIA with iodine improved detection of CIN2+ in women who were hrHPV DNA positive but was not significantly better than VIA alone., Trial Registration Number: NCT05125380., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2024. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.)

Objectives: As cervical cancer screening programs are implemented and expanded, an increasing number of women require loop electrosurgical excision procedure (LEEP) for treatment of pre-invasive cervical disease. Our objective was to describe the pathological results of LEEP specimens performed as part of the MULHER study and identify factors associated with positive LEEP margins., Methods: The MULHER study enrolled 9014 women who underwent HPV testing followed by visual assessment for treatment (VAT) using visual inspection with acetic acid (VIA) and thermal ablation for those with positive results. Participants with lesions ineligible for ablation underwent LEEP. Pathology reports were reviewed for specimen size/volume, number of fragments, pathological diagnosis and margin status. Multivariable regression analysis was performed to identify variables associated with positive LEEP margins., Results: 169 participants underwent LEEP. The median age was 38 years (range 30-49). 65.1% were women living with HIV. Pathological diagnosis was available for 154 patients and included cancer (n=6, 3.9%); cervical intraepithelial neoplasia (CIN) 2/3 (n=75, 48.7%); CIN 1 (n=67, 43.5%); and normal/benign findings (n=6,3.9%). 31.8% of LEEP specimens were removed in more than one fragment. The mean specimen volume was 2.9 cm 3 (range 0.2-15.0). LEEP margin status was available for 130 patients. Positive margins (ectocervical/endocervical only, or both) were noted in 76 (58.5%) patients and associated with HIV+status (p=0.0499) and a diagnosis of CIN 2 or worse (p=0.0197). There were no associations between margin status and age, number of fragments or specimen volume., Conclusion: Our results showed a high number of LEEP specimens with positive margins. Additional evaluation is needed to better understand the characteristics of precancerous cervical lesions in this high-risk population. As cervical cancer screening programs are scaled in Mozambique and other lower-resource countries, there is a need to train providers to perform high-quality LEEP and for accurate and timely pathological interpretation., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Currently, eight million people in the United States suffer from cancer and it is a major global health concern. Early detection and interventions are urgently needed for all cancers, including colorectal cancer. Colorectal cancer is the third most common type of cancer worldwide. Based on the diagnostic efforts to general awareness and lifestyle choices, it is understandable why colorectal cancer is so prevalent today. There is a notable lack of awareness concerning the impact of this cancer and its connection to lifestyle elements, as well as people sometimes mistaking symptoms for a different gastrointestinal condition. Artificial intelligence (AI) may assist in the early detection of all cancers, including colorectal cancer. The usage of AI has exponentially grown in healthcare through extensive research, and since clinical implementation, it has succeeded in improving patient lifestyles, modernizing diagnostic processes, and innovating current treatment strategies. Numerous challenges arise for patients with colorectal cancer and oncologists alike during treatment. For initial screening phases, conventional methods often result in misdiagnosis. Moreover, after detection, determining the course of which colorectal cancer can sometimes contribute to treatment delays. This article touches on recent advancements in AI and its clinical application while shedding light on why this disease is so common today., (©2024 American Association for Cancer Research.)

Bladder cancer (BCa) exhibits the escalating incidence and mortality due to the untimely and inaccurate early diagnosis. Urinary exosome metabolites, carrying critical tumor cell information and directly related to bladder, emerge as promising non-invasive diagnostic biomarkers of BCa. Herein, the magnetic 3D ordered macroporous zeolitic imidazolate framework-8 (magMZIF-8) is synthesized and used for efficient urinary exosome isolation. Notably, beyond retaining the single crystals and micropores of conventional ZIF-8, MZIF-8 is further enhanced with highly oriented and ordered macropores (150 nm) and the large specific surface area (973 m 2 ·g -1 ), which could enable the high purity and yield separation of exosomes via leveraging the combination of size exclusion, affinity, and electrostatic interactions between magMZIF-8 and the surfaces of exosome. Furthermore, the magnetic and hydrophilic properties of magMZIF-8 will further simplify the process and enhance the efficiency of separation. After conditional optimization, a 50 mL of urine is sufficient for exosome metabolomics analysis, and the time for isolating exosomes from 42 urine samples was 2 hours only. Incorporating machine learning algorithms with LC-MS/MS analysis of the metabolic patterns obtained from isolated exosomes, early-stage BCa patients were differentiated from healthy controls, with area under the curve (AUC) value of 0.844-0.9970 in the training set and 0.875-1.00 in the test set, signifying its potential as a reliable diagnostic tool. This study offers a promising approach for the non-invasive and efficient diagnosis of BCa on a large scale via exosome metabolomics., (© 2024. The Author(s).)

Introduction: Microwave imaging presents several potential advantages including its non-ionising and harmless nature. This open, multicentric, interventional, prospective, non-randomised trial aims to validate MammoWave's artificial intelligence (AI)-based classification algorithm, leveraging microwave imaging, to achieve a sensitivity exceeding 75% and a specificity exceeding 90% in breast screening., Methods and Analysis: 10 000 volunteers undergoing regular mammographic breast cancer screening will be recruited across 9 European centres and invited to participate in the clinical study, involving MammoWave testing on both breasts. MammoWave results will be checked against the reference standard, to be intended as the output of conventional breast examination path (with histological confirmation of cancer cases) with 2 years follow-up. Anonymised clinical and MammoWave's results, including microwave images, associated features and a label provided by the AI-based classification algorithm, will be collected and stored in a dedicated electronic case report form. The prospective study will involve a comparative analysis between the output of the conventional breast examination path (control intervention) and the labels provided by MammoWave's AI system (experimental intervention). These labels will categorise breasts into two groups: breast With Suspicious Finding, indicating the presence of a suspicious lesion or No Suspicious Finding, indicating the absence of a lesion or the presence of a low-suspicion lesion. This trial aims to provide evidence regarding the novel MammoWave's AI system for detecting breast cancer in asymptomatic populations during screening., Ethics and Dissemination: This study was approved by the Research Ethics Committee of the Liguria Region (CET), Italy (CET-Liguria: 524/2023-DB id 13399), the Research Ethics Committee of Complejo Hospitalario de Toledo (CEIC), Spain (CEIC-1094), the National Ethics Committee for Clinical Research (CEIC), Portugal (CEIC-2311KC814), the Bioethical Committee of Pomeranian Medical University in Szczecin, Poland (KB-006/23/2024) and the Zurich Cantonal Ethics Commission, Switzerland (BASEC 2023-D0101). The findings of this study will be disseminated through academic and scientific conferences as well as peer-reviewed journals., Trial Registration Number: NCT06291896., Competing Interests: Competing interests: NG, GT, BK and Alessandra Bigotti are employed by UBT—Umbria Bioengineering Technologies Srl. NG and GT are shareholders of UBT—Umbria Bioengineering Technologies. UBT—Umbria Bioengineering Technologies Srl manufactured the microwave imaging device known as MammoWave. This does not alter our adherence to BMJ Open policies., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Prostate cancer is the most diagnosed noncutaneous malignancy and the second most common cause of cancer death among men in the United States. Risk factors include older age, family history of prostate cancer, and Black race. Screening via prostate-specific antigen testing may lead to a small reduction in prostate cancer-specific mortality, with no reduction in all-cause mortality, but it can cause significant harms related to false-positive test results, unnecessary biopsies, overdiagnosis, and overtreatment. Shared decision-making is strongly recommended by all national guidelines before initiating screening. Most guidelines recommend screening every 2 to 4 years in men 55 to 69 years of age at average risk. After a positive prostate-specific antigen test result (more than 4 ng/mL), the test should be repeated. If the prostate-specific antigen level is still elevated, next steps include multiparametric magnetic resonance imaging, assessment of urine or blood biomarkers, and referral to urology. Active surveillance is increasingly accepted as the preferred standard of care for patients with newly diagnosed low-risk prostate cancer, because it is associated with similar long-term survival and better quality of life than curative treatment. The primary intent of screening is to identify patients with clinically significant prostate cancer who may benefit from curative treatment while minimizing the detection of clinically insignificant cancer.

Background Deep learning (DL) algorithms have shown promising results in mammographic screening either compared to a single reader or, when deployed in conjunction with a human reader, compared with double reading. Purpose To externally validate the performance of three DL algorithms as mammographic screen readers in an independent UK data set. Materials and Methods Three commercial DL algorithms (DL-1, DL-2, and DL-3) were retrospectively investigated from January 2022 to June 2022 using consecutive full-field digital mammograms collected at two UK sites during 1 year (2017). Normal cases with 3-year follow-up and histopathologically proven cancer cases detected either at screening (that round or next) or within the 3-year interval were included. A preset specificity threshold equivalent to a single reader was applied. Performance was evaluated for stand-alone DL reading compared with single human reading, and for DL reading combined with human reading compared with double reading, using sensitivity and specificity as the primary metrics. P < .025 was considered to indicate statistical significance for noninferiority testing. Results A total of 26 722 cases (median patient age, 59.0 years [IQR, 54.0-63.0 years]) with mammograms acquired using machines from two vendors were included. Cases included 332 screen-detected, 174 interval, and 254 next-round cancers. Two of three stand-alone DL algorithms achieved noninferior sensitivity (DL-1: 64.8%, P < .001; DL-2: 56.7%, P = .03; DL-3: 58.9%, P < .001) compared with the single first reader (62.8%), and specificity was noninferior for DL-1 (92.8%; P < .001) and DL-2 (96.8%; P < .001) and superior for DL-3 (97.9%; P < .001) compared with the single first reader (96.5%). Combining the DL algorithms with human readers achieved noninferior sensitivity (67.0%, 65.6%, and 65.4% for DL-1, DL-2, and DL-3, respectively; P < .001 for all) compared with double reading (67.4%), and superior specificity (97.4%, 97.6%, and 97.6%; P < .001 for all) compared with double reading (97.1%). Conclusion Use of stand-alone DL algorithms in combination with a human reader could maintain screening accuracy while reducing workload. Published under a CC BY 4.0 license. Supplemental material is available for this article.

Background: Detection of cancer at the early stage currently offers the only viable strategy for reducing disease-related morbidity and mortality. Various approaches for multi-cancer early detection are being explored, which largely rely on capturing signals from circulating analytes shed by tumors into the blood. The fact that biomarker concentrations are limiting in the early stages of cancer, however, compromises the accuracy of these tests. We, therefore, adopted an alternate approach that involved interrogation of the serum metabolome with machine learning-based data analytics. Here, we monitored for modulations in metabolite patterns that correlated with the presence or absence of cancer. Results obtained confirmed the efficacy of this approach by demonstrating that it could detect a total of 15 cancers in women with an average accuracy of about 99%., Aims: To further increase the scope of our test, we conducted an investigator-initiated clinical trial involving a total of 6445 study participants, which included both cancer patients and non-cancer volunteers. Our goal here was to maximize the number of cancers that could be detected, while also covering cancers in both females and males., Methods and Results: Metabolites extracted from individual serum samples were profiled by ultra-performance liquid chromatography coupled to a high-resolution mass spectrometer using an untargeted protocol. After processing, the data were analyzed by our cancer detection machine-learning algorithm to differentiate cancer from non-cancer samples. Results revealed that our test platform could indeed detect a total of 30 cancers, covering both females and males, with an average accuracy of ~98%. Importantly, the high detection accuracy remained invariant across all four stages of the cancers., Conclusion: Thus, our approach of integrating untargeted metabolomics with machine learning-powered data analytics offers a powerful strategy for early-stage multi-cancer detection with high accuracy., Trial Registration: Registration No: CTRI/2023/03/050316., (© 2024 The Author(s). Cancer Reports published by Wiley Periodicals LLC.)

IFO'S communication campaign for the Italian Lung Screening Network (RISP) study, used multiple online and offline channels to engage not only smokers but a diverse audience. Out-reach activities and lifelong learning helped to promote healthy lifestyles, research findings and precision medicine. The campaign has increased the enrollment in the screening program, which in IFO, two years after 'start-up, is 3300. The pilot study targets smokers and former smokers aged 55 to 75, for prevention and early detection of lung cancer. Funded by the Ministry of Health, it involves 19 Italian centers to enroll 10,000 people. The ultimate goal is the inclusion of lung screening in the Essential Levels of Care (LEA) that is, the services that the National Health Service is required to provide to all citizens, free of charge. Subjects involved perform multilayer low-dose CT scan of the chest and blood sampling with liquid biopsy. The success of the campaign rewards the communication strategy, multidisciplinary collaboration, and activities always in synergy with the mission of the IFOs committed to: "spreading" clinical excellence; promoting citizen empowerment; considering correct information an institutional duty because it is part of treatment and prevention.

Objectives: With wide application of computed tomography (CT) in early lung cancer screening, solitary pulmonary nodules (SPNs) are frequently detected. Due to their high etiological diversity and potential for malignancy, rapid and accurate identification and malignant SPNs are crucial in the clinical management. In the present study, plasma exosomal microRNAs were identified and evaluated as sensitive and specific indicators for malignant SPNs., Materials and Methods: Exosomal miRNAs isolated from the plasmas of pathologically confirmed patients with SPN (four malignant and four benign, designated as the screening set) were subjected for high throughput sequencing and eight candidate miRNAs were selected. The pre-operation plasma levels of the candidate miRNAs in 77 patients with SPN (48 malignant and 29 benign, designated as the identification set) were detected by quantitative PCR, five miRNAs were identified as potential biomarkers for malignant SPNs, and the diagnostic values of the five miRNAs each alone or combined were then analyzed by AUROC analysis. The prediction values of the identified miRNAs were further evaluated in 95 patients with SPN (double blind, 74 malignant and 21 benign, designated as the validation set)., Results: High-throughput sequencing identified 45 miRNAs with statistical differences between benign and malignant SPNs. Among the eight candidate miRNAs in the identification set, miR-1-3p alone had the best diagnostic value, with the sensitivities and specificities of 89.6% and 100% for malignant SPNs. Unexpectedly, when miR-1-3p was combined with miR-99a-5p, both the sensitivity and specificity reached 100% for malignant SPNs. miR-1-3p+miR-125b-5p and miR-1-3p+miR-218-5p were also good indicators of malignant SPNs with sensitivities of 95.8% and 97.9%, specificities of 100% and 96.6%. Further analysis of these microRNA combinations in the validation set indicated that the PPV were 91.4%, 97.4%, and 93.5% and the NPV were 100%, 100%, and 88.9% for miR-1-3p+miR-99a-5p, miR-1-3p+miR-218-5p, and miR-1-3p+miR-125b-5p, with the sensitivities were 100%, 100%, and 97.3% and the specificities were 66.7%, 90.5%, and 76.2% for miR-1-3p+miR-99a-5p, miR-1-3p+miR-218-5p, and miR-1-3p+miR-125b-5p, respectively., Conclusions: Through high throughput sequencing, qPCR determination of plasma microRNAs and AUROC analysis, miR-1-3p combined with miR-99a-5p, miR-125b-5p, or miR-218-5p have been found to be sensitive and specific indicators of malignant SPNs in both the identification and validation sets. Our results indicate that the panels of plasma miRNAs can be used as diagnostic biomarkers for malignant SPNs., (© 2024 The Author(s). Clinical Respiratory Journal published by John Wiley & Sons Ltd.)

High-risk human papillomavirus (HR-HPV) testing, utilizing both DNA and RNA methods, offers enhanced sensitivity compared to cytology for detecting high-grade cervical intraepithelial neoplasia (CIN2+). Meanwhile, HR-HPV E6 and E7 mRNAs are more likely to differentiate the transient infection from the persistent than DNA. Aptima HPV can not only detect HPV mRNA but also HPV DNA though it is much more efficient at detecting HPV RNA than DNA. Currently, there are few studies on the distribution of HPV E6 and E7 mRNA and DNA in the same individual. It is interesting to compare the clinical performance of the Onclarity and Aptima HPV assays and to assess variations in viral load across different histological grades at both DNA and mRNA levels. The analysis included 1607 women (902 from a cervical cancer screening population and 705 inpatients and outpatients), with cervical cytological samples tested using the Aptima and Onclarity HPV assays. Both assays demonstrated high agreement for HPV types 18/45 and 16. Signal-to-cutoff (S/CO) values and Ct values for various HR-HPV types increased with histological severity from normal tissue to cancer. Notably, HPV18 Ct values exceeded those for HPV16 and 45 in women with ≥ CIN1 lesions but decreased sharply in cancer cases. Across the screening population, both assays showed similar sensitivity and predictive values for detecting CIN2+ lesions. The area under the curve (AUC) for CIN2+ and CIN3+ detection in the study population was robust (CIN2+: 0.880, 0.863; CIN3+: 0.881, 0.863). The DNA level for various HR-HPV types increased with histological severity from normal tissue to cancer, which might impact the performance of Aptima HPV assay. Both assays showed similar sensitivity and predictive values for detecting CIN2+ lesions., (© 2024 Wiley Periodicals LLC.)

Introduction: Individuals who develop new-onset diabetes have been identified as a high-risk cohort for pancreatic cancer (PC), exhibiting an incidence rate nearly 8 times higher than the general population. Hence, the targeted screening of this specific cohort presents a promising opportunity for early pancreatic cancer detection. We aimed to develop and validate a novel model capable of identifying high-risk individuals among those with new-onset diabetes., Methods: Employing the UK Biobank cohort, we focused on those developing new-onset diabetes during follow-up. Genetic and clinical characteristics available at registration were considered as candidate predictors. We conducted univariate regression analysis to identify potential indicators and used a 5-fold cross-validation method to select optimal predictors for model development. Five machine learning algorithms were used for model development., Results: Among 12,735 patients with new-onset diabetes, 100 (0.8%) were diagnosed with PC within 2 years. The final model (area under the curve, 0.897; 95% confidence interval, 0.865-0.929) included 5 clinical predictors and 24 single nucleotide polymorphisms. Two threshold cut-offs were established: 1.28% and 5.26%. The recommended 1.28% cut-off, based on model performance, reduces definitive testing to 13% of the total population while capturing 76% of PC cases. The high-risk threshold is 5.26%. Utilizing this threshold, only 2% of the population needs definitive testing, capturing nearly half of PC cases., Conclusions: We, for the first time, combined clinical and genetic data to develop and validate a model to determine the risk of pancreatic cancer in patients with new-onset diabetes using machine learning algorithms. By reducing the number of unnecessary tests while ensuring that a substantial proportion of high-risk patients are identified, this tool has the potential to improve patient outcomes and optimize healthcare sources., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Background Studies suggest that readers experience perceptual adaptation when interpreting batched screening mammograms, which may serve as a mechanism for improved performance. Purpose To analyze clinical digital breast tomosynthesis (DBT) screening data to evaluate changes in reader performance during sequential batch reading. Materials and Methods This observational retrospective study used data from the radiology information system collected for screening DBT examinations performed from January 2018 to December 2019. The reference standard was established based on pathology results, if applicable, or imaging findings at 1-year follow-up. Examinations were aggregated into batches, defined as a sequence of cases for a given reader with differences in interexamination time of 10 minutes or less. Mixed-effect models were used to evaluate performance and timing across batch positions. Statistical adjustments accounted for potential confounders, including patient characteristics (age, breast density), reading factors (day of week, time of day), and between-reader heterogeneity. Results The dataset included 121 652 examinations (median patient age, 61 years [IQR, 53-69 years]), including 1081 cancers interpreted by 15 radiologists. Unadjusted false-positive rates decreased from an averaged 15.5% at the first within-batch examination to 10.5% after three sequentially read examinations ( P < .001), without a significant change in sensitivity (82.6% vs 84.2%; P = .15). The interpretation time consistently decreased, achieving a substantial reduction in longer batches (average 2.8 to 2.2 minutes for noncancer examinations; P < .001). Adjustment for sampling bias and confounders (patient age, breast density, day of week, time of day; all P < .005) reduced the effect on false-positive rates (11.5% to 9.4% after three examinations; P < .001) and interpretation time (3.2 to 2.7 minutes for noncancer examinations; P < .001). Conclusion Radiologists showed improved recall rates and interpretation times without change in sensitivity over the course of batch reading of DBT screening examinations. © RSNA, 2024 See also the editorial by Iima and Satake in this issue.

One-dose prophylactic HPV vaccination of pre-adolescents may reduce cervical cancer deaths dramatically in lower-resource settings, but the benefits of achieving immediate high coverage among pre-adolescents would not be realized for 20 to 40 years. Prophylactic vaccine efficacy is reduced after sexual debut, and current therapeutic intervention candidates designed to treat existing HPV infections or precancerous lesions have yielded insufficient evidence to warrant widespread use. However, we are developing a feasible, scalable, high-quality cervical screening approach that could prevent hundreds of thousands of deaths, while we work to achieve high coverage of one-dose vaccination for adolescent cohorts. A time-limited "one screen" campaign approach for lower-resource settings could complement parallel efforts to achieve high coverage with one-dose vaccination. This screen-triage-treat strategy would target the highest risk groups of screening age (ie, 25 to 49 years) for once-in-a-lifetime HPV testing of self-collected samples using a low-cost accurate HPV test; subsequent triage relying on extended genotyping and a validated deep-learning algorithm for automated visual evaluation (AVE) would stratify management based on risk to provide treatment for those most likely to develop cancer without overburdening health care systems. Early efficacy of this approach has been demonstrated in 9 countries within the HPV-AVE (PAVE) Study Consortium. We estimate that the cost per death averted of a screen-triage-treat campaign is of similar magnitude to prophylactic vaccination. We do not envision perpetual investment in ubiquitous brick-and-mortar screening programs if "one dose, one screen" is implemented with high coverage and targets the highest-risk populations. In collaboration with in-country stakeholders, efforts to ensure acceptability, risk communication, and cost-effectiveness are underway., (Published by Oxford University Press 2024.)

Background Breast nonmass lesions (NMLs) are observed at screening and diagnostic US. However, knowledge is limited on imaging features of NMLs at screening US. Purpose To identify features of NMLs at screening US that are suspicious for malignancy based on mammographic findings. Materials and Methods This retrospective, multicenter study included asymptomatic women who underwent screening US between January 2012 and December 2019. Eligible women had NMLs at US, concurrent screening mammography, and record of a final diagnosis. Logistic regression analyses were used to identify factors associated with malignancy. The diagnostic performance of each sonographic feature according to mammographic findings was calculated. A reader study was performed to assess interreader agreement for sonographic features. Results Among 993 NMLs in 993 patients (mean age, 50 years ± 9 [SD]), 914 (92.0%) were benign and 79 (8.0%) were malignant. Mean size was larger for malignant NMLs than for benign NMLs (2.6 cm ± 1.1 vs 1.9 cm ± 0.8; P < .001). In multivariable analysis, associated calcifications (odds ratio [OR], 21.6 [95% CI: 8.0, 58.2]; P < .001), posterior shadowing (OR, 6.9 [95% CI: 2.6, 18.4]; P < .001), segmental distribution (OR, 6.2 [95% CI: 2.7, 14.4]; P < .001), mixed echogenicity (OR, 5.0 [95% CI: 1.8, 14.0]; P < .001), and size (OR, 1.5 [95% CI: 1.1, 2.1]; P = .01) at US were associated with malignancy. Associated calcifications, posterior shadowing, segmental distribution, and mixed echogenicity showed positive predictive values (PPVs) of 44%, 22%, 22.9%, and 16.6%, respectively. Having a negative mammogram was associated with a lower malignancy rate (2.8% vs 28.8%) and lower PPVs for sonographic features (0.7%-10.4% vs 24%-55%) than having a positive mammogram. Interreader agreement for sonographic features was good to excellent (Fleiss κ 95% CI lower bound range, 0.63-0.81). Conclusion Calcifications, posterior shadowing, segmental distribution, and mixed echogenicity associated with NMLs can be considered suspicious features for malignancy at screening US. As malignancy rates and PPVs differ according to mammographic abnormalities, combined assessment is mandatory. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Grimm in this issue.

Biomarkers are molecules such as proteins, genes, or other substances that may be tested to determine the stage of the tumor in a patient. The role of prostate cancer biomarkers is pivotal and the combination of prostate cancer immunotherapy with efficient biomarkers has emerged as a beneficial treatment strategy and its use has increased rapidly. The two primary objectives of this current prostate cancer early detection programs were recognizing non-symptomatic individuals with prostate cancer requiring prostatic core biopsy and identifying men with prostate cancer who might benefit from definitive medical treatment. The progress that has been made so far in the identification of the biomarkers that can be used for the classification, prediction and prognostication of prostate cancer, and as major targets for its clinical intervention has been well summarized in this review., Competing Interests: The authors have nothing to disclose., (© The Korean Urological Association.)