Int. J. Cancer [JOURNAL]
Sun
200 papers
A Serum lncRNA Signature Determines Oncogenic YAP Activity in Cancer Patients.
Rose F, El-Ekiaby N, Wehling L … +22 more , Weiler SME, Schmitt J, Tóth M, Pedrini F, Damle-Vartak A, Sticht C, Pellegrino R, Fawzy IO, Hamad MHM, Negm M, Omar D, Soliman HE, Esmat G, Longerich T, Illig T, Köhler BC, Saborowski A, Bantel H, Vogel A, Schirmacher P, Abdelaziz AI, Breuhahn K
Int J Cancer · 2026 Jun · PMID 42338005 · Publisher ↗
Biomarkers are typically identified by comparing human samples such as tissues and serum. However, reliable markers for transcriptionally active oncogenes remain elusive due to tumor heterogeneity and confounding signals...
Biomarkers are typically identified by comparing human samples such as tissues and serum. However, reliable markers for transcriptionally active oncogenes remain elusive due to tumor heterogeneity and confounding signals from non-tumorous cells. We hypothesize that in vitro screening is sufficient to identify a long non-coding RNA (lncRNA) signature that is a specific marker for oncogenic transcriptional regulators. Exemplified for the Hippo pathway effectors, we integrated experimental NGS and cancer patient expression data with bioinformatics approaches to identify a yes-associated protein (YAP)-specific lncRNA signature in hepatocellular carcinoma (HCC) cells. The lncRNAs in this signature include CYTOR, MIR4435-2HG, SNHG1, and SNHG17, which partly promote HCC cell proliferation and control the sensitivity to YAP/TEA domain transcription factor (TEAD)-targeted inhibition. In HCC tissues, the lncRNA signature is associated with increased nuclear enrichment of YAP, the expression of YAP target genes, and poor clinical outcomes in patients. This association was also confirmed in cells and tissues of other malignancies, including lung adenocarcinoma (LUAD). Notably, the lncRNA signature is detectable in the serum of HCC patients and predicts YAP activation in tumor tissues. In summary, the Hippo pathway-associated lncRNA signature provides a readout for oncogenic YAP activity across cancers, suggesting its potential as a pan-cancer biomarker. Our results highlight oncogene-specific lncRNA signatures as valuable tools for diagnostics, therapy selection, and treatment monitoring.
Immune Markers and Risk of Pancreatic Cancer in the European EPIC Cohort.
Katzke VA, Chen Y, Dutta S … +26 more , Canzian F, Andersen JLM, Rostgaard-Hansen AL, Bouteille L, Rebours V, Truong T, Schulze MB, Bendinelli B, Pala V, Simeon V, Tumino R, Sacerdote C, Vermeulen R, Kolijn PM, Elias SG, Crous-Bou M, Sánchez MJ, Jimenez-Zabala A, Huerta JM, Guevara M, Wareham N, Breeur M, Johansson M, Yarmolinsky J, Campa D, Kaaks R
Int J Cancer · 2026 Jun · PMID 42334072 · Publisher ↗
The immune system is a major driver in pancreatic cancer development. Several prospective cohort studies have found associations for single immune system-derived proteins such as IL6 or CRP, but results are inconclusive,...
The immune system is a major driver in pancreatic cancer development. Several prospective cohort studies have found associations for single immune system-derived proteins such as IL6 or CRP, but results are inconclusive, and Omics-based research is scarce. Hence, we aimed to investigate associations of a comprehensive protein panel with the risk of pancreatic cancer. Within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, 92 immune proteins were measured in baseline blood samples of 406 incident pancreatic cancer cases and 406 sex- and age-matched controls, using the Olink Immuno-Oncology panel. Multivariable adjusted conditional logistic regression was used to estimate odds ratios (OR, 95% CI) for protein levels in association with pancreatic cancer risk. Eight biomarkers were associated with pancreatic cancer risk (MMP12, LAMP3, CD28, IL-6, IL-12, FASLG, PD-L2, and PDCD1) but only MMP12 was significantly associated after multivariable adjustments for confounders and the seven proteins, with OR = 1.56 (95% CI: 1.20-2.03) for a doubling in protein concentration. After correction for multiple testing, none of the proteins were associated with risk. Restricting analyses to cases diagnosed within the first 4 years and 4-8 years after recruitment resulted in OR of 1.89 (95% CI: 1.28-2.80) and 1.37 (95% CI: 1.01-1.86) for MMP12, respectively. Higher levels of MMP12 were associated with pancreatic cancer risk specifically in those diagnosed shortly after recruitment, while other immune-related factors were not associated with risk. Further cohort studies are needed to confirm our initial findings.
Cascade Testing Barriers: How to Overcome?
Lim T, Caeser R, Ngeow J
Int J Cancer · 2026 Jun · PMID 42334069 · Publisher ↗
Hereditary cancer syndromes account for 5%-10% of all cancers. Identifying pathogenic variants in a proband guides clinical management and enables targeted testing of at-risk relatives through cascade testing. By clarify...
Hereditary cancer syndromes account for 5%-10% of all cancers. Identifying pathogenic variants in a proband guides clinical management and enables targeted testing of at-risk relatives through cascade testing. By clarifying carrier status, relatives can adopt early surveillance and undergo risk-reducing interventions, while noncarriers are reassured. Despite clear clinical benefits and cost-effectiveness, cascade uptake remains low worldwide, averaging only ~15%-30%. This review examines facilitators and barriers to cascade testing, and outlines strategies to strengthen uptake. Barriers that exist across three interrelated levels are as follows: Individual, provider and health system. At the individual level, psychosocial concerns such as stigma, discrimination and fear of causing distress to family may limit disclosure. Limited health literacy, misconceptions and cultural norms may further reduce uptake, particularly among underserved groups. Overcoming these challenges requires culturally sensitive, patient-friendly communication to empower families to make informed choices. At the provider level, ethical dilemmas around confidentiality, confidence gaps among non-genetics professionals and shortage of genetic counsellors constrain service delivery. Embedding genetic counsellors in the wider healthcare setting, upskilling non-genetics professionals and normalising conversations about cascade testing can mitigate these barriers. At the health system level, prohibitive costs, fragmented referral pathways and administrative inefficiencies impede access, while legal gaps around genetic discrimination discourage uptake. Sustainable financing models, streamlined care pathways, legislation and international collaborations are needed to support equitable implementation of cascade testing. Cascade testing remains a powerful means for cancer prevention. Addressing individual, professional, and structural barriers through context-specific, multi-level solutions is key to realising its potential and advancing precision medicine globally.
Incidence Trends of Early-Onset Colorectal Cancer in Germany: A Registry-Based Study From 2003 to 2023.
Voigtländer S, Kajüter H, Wellmann I … +5 more , Szentkirályi A, Holleczek B, Arndt V, Müller-Nordhorn J, ALSTER Working Group
Int J Cancer · 2026 Jun · PMID 42333995 · Publisher ↗
Motivated by studies on early-onset colorectal cancer (EO CRC, below 50 years) from the United States (US) and elsewhere, this study aimed to provide national incidence trends of EO CRC for Germany. We retrieved colorect...
Motivated by studies on early-onset colorectal cancer (EO CRC, below 50 years) from the United States (US) and elsewhere, this study aimed to provide national incidence trends of EO CRC for Germany. We retrieved colorectal cancer cases (ICD-10 codes C18-C20) using pooled data from German cancer registries with high-quality data. Appendix (C18.1) was excluded from the main analyses and investigated separately. We calculated age-standardised incidence rates (ASR) by calendar year, age group, sex, tumour site, histological subtype, tumour size, grading and estimated corresponding average annual percent changes (AAPC). For comparison, US cancer registry data was drawn from the Surveillance, Epidemiology, and End Results programs 21 population-based registries (SEER 21). From 2003 to 2023, ASRs of EO CRC (C18-C20 excluding C18.1) increased for men (AAPC: 0.8%) and women (AAPC: 0.9%) in Germany. By 10-year age groups, the increase was limited to men and women aged 20-29 years (AAPC males: 3.3%; AAPC females: 3.9%) and 30-39 years (AAPC males: 2.2%; AAPC females: 2.0%). For appendix cancer (C18.1), ASRs were rising for all age groups below 50 years of age. Increases for both colorectal cancer (excluding the appendix) and appendix cancer tended to be higher for cancers with good prognosis (neuroendocrine neoplasms, small size, low grading). In contrast to the US, Germany had a substantially lower EO CRC incidence in 2003 that increased at a slower pace. It is important to monitor future EO CRC incidence trends. The causes of the observed trends remain unclear.
5-Aminolevulinic Acid Photodynamic Therapy for Non-Lesional Persistent High-Risk HPV Infection: A Comparative Cohort Study With Interferon.
He R, Guo W, Hu Y … +4 more , Wu A, Gu L, Hong Z, Qiu L
Int J Cancer · 2026 Jun · PMID 42332975 · Publisher ↗
Persistent high-risk human papillomavirus (HR-HPV) infection drives cervical carcinogenesis, yet effective treatments for patients without histologically confirmed cervical lesions are lacking. Although five-aminolevulin...
Persistent high-risk human papillomavirus (HR-HPV) infection drives cervical carcinogenesis, yet effective treatments for patients without histologically confirmed cervical lesions are lacking. Although five-aminolevulinic acid photodynamic therapy (ALA-PDT) effectively treats cervical lesions and associated HR-HPV, its efficacy for clearing HR-HPV in non-lesional patients is unclear. We aim to compare the efficacy of ALA-PDT versus interferon (IFN) in treating persistent HR-HPV infection in patients without cervical lesions. This real-world cohort study included 157 patients receiving three sessions of ALA-PDT and 114 patients receiving 3 courses total of IFN therapy. The primary outcome was HR-HPV complete clearance at 6- and 12-month post-treatment. At 6 months, complete clearance rates were 56.9% (82/144) in the PDT group versus 15.3% (13/85) in the IFN group (p < 0.001). At 12 months, rates were 67.0% (59/88) versus 28.3% (26/92) (p < 0.001). Generalized estimating equations (GEE) analysis confirmed PDT was significantly superior to IFN in reducing persistent infection risk (adjusted odds ratio [aOR] = 0.114, 95% CI: 0.054-0.242, p < 0.001). Longer infection duration (≥ 24 vs. 6-23 months) (aOR = 2.334, 95% CI: 1.352-4.030, p = 0.002) and increasing age (per year) (aOR = 1.025, 95% CI: 1.003-1.048, p = 0.027) were independently associated with higher persistence risk. Adverse events (mild pain and vaginal discharge) occurred in 5.1% of patients. ALA-PDT demonstrates superior and sustained efficacy over IFN for clearing persistent HR-HPV infection in patients without cervical lesions. Older age and longer infection duration are significant risk factors for treatment failure.
The German ONKOPEDIA Guideline for Myelofibrosis in 2025-Recommendations of an MPN Expert Panel of the German Society for Hematology and Oncology (DGHO).
Griesshammer M, Al-Ali HK, Baerlocher GM … +6 more , Döhner K, Koschmieder S, Kröger N, Petrides PE, Wolf D, Heidel FH
Int J Cancer · 2026 Jun · PMID 42324205 · Publisher ↗
The recently published ONKOPEDIA guideline on myelofibrosis, issued under the auspices of the German Society of Hematology and Oncology (DGHO), provides an updated, evidence-based framework for the diagnosis and manageme...
The recently published ONKOPEDIA guideline on myelofibrosis, issued under the auspices of the German Society of Hematology and Oncology (DGHO), provides an updated, evidence-based framework for the diagnosis and management of this rare, chronic myeloproliferative neoplasm. Developed by a panel of experts (including Germany, Austria and Switzerland) nominated by the DGHO, the guideline reflects a structured and consensus-oriented process in which internationally recognized specialists in hematology critically reviewed the available evidence, revised the written draft, and engaged in multiple rounds of discussion to ensure consistency, clinical relevance, and scientific rigor. This update builds upon the foundation of the previously available ONKOPEDIA guideline (accessible at www.onkopedia.com), but extends and refines the recommendations in light of several important recent developments.
Primary Myelofibrosis (PMF)-The German ONKOPEDIA Guideline 2025.
Griesshammer M, Al-Ali HK, Baerlocher GM … +6 more , Döhner K, Koschmieder S, Kröger N, Petrides PE, Wolf D, Heidel FH
Int J Cancer · 2026 Jun · PMID 42324204 · Publisher ↗
Myelofibrosis (MF) is a rare, clonal disorder of pluripotent hematopoietic stem and progenitor cells. It is characterized by abnormal proliferation of hematopoiesis, associated with pathologically increased fibrosis in t...
Myelofibrosis (MF) is a rare, clonal disorder of pluripotent hematopoietic stem and progenitor cells. It is characterized by abnormal proliferation of hematopoiesis, associated with pathologically increased fibrosis in the bone marrow, which is primarily caused by activation of the JAK2 signaling pathway. Myelofibrosis (MF) may occur de novo as primary myelofibrosis (PMF), or secondarily as a consequence of polycythemia vera (PV) or essential thrombocythemia (ET), termed post-PV-MF and post-ET-MF, respectively. The latter two are collectively referred to as secondary myelofibrosis. The most recent updates of the diagnostic criteria by the WHO and ICC were published in 2022. These revisions defined prefibrotic primary myelofibrosis (pre-PMF) as a distinct subentity alongside "classic" overtly fibrotic PMF and secondary myelofibrosis. A hallmark of pre-PMF is an initial isolated thrombocytosis, whereas in overt MF, anemia is frequently present already at diagnosis. Splenomegaly is also more commonly detected at diagnosis in overt fibrotic MF than in pre-PMF. The prognosis of MF is determined by patient age, the presence of constitutional symptoms, as well as hematologic and genetic parameters. Increasingly, cytogenetic and molecular genetic markers play a decisive role. The most common causes of death in MF include transformation to acute myeloid leukemia, infections, and cardiovascular complications. The only potentially curative treatment is allogeneic stem cell transplantation (alloSCT), which is generally indicated in transplant-eligible patients with unfavorable prognosis, that is, those classified as high- or very-high risk according to the MIPSS70+ v2.0. For symptomatic treatment of MF, a variety of therapeutic options are available. In recent years, oral therapy with the JAK1/2 inhibitor ruxolitinib has become the standard of care. Since 2021, the JAK2/FLT3 inhibitor fedratinib has also been approved in the EU (note: in Switzerland, fedratinib will no longer be available as of February 28, 2025, as Swissmedic did not extend its time-limited approval). Since 2024, the JAK1/2 and ACVR1/ALK2 inhibitor momelotinib has been approved for MF treatment in the EU (irrespective of risk category) and in Switzerland (restricted to intermediate- or high-risk disease) for patients with moderate or severe anemia and/or after prior treatment with ruxolitinib. Compared to the other two JAK inhibitors, momelotinib is particularly effective in patients with clinically symptomatic moderate to severe anemia. Results from studies investigating additional JAK inhibitors, combination therapies, and novel agents have also demonstrated significant efficacy and point toward future therapeutic developments, although these approaches are not yet available for routine clinical practice.
Survival Following Neoplastic Disease in Individuals With Neurofibromatosis 1-A National Danish Population-Based Cohort Study.
Doherty MA, Grell K, Hove H … +10 more , Handrup MM, Østergaard JR, Krøyer A, Nielsen TT, Hjalgrim H, Mulvihill JJ, Wohlfahrt J, Hasle H, Ejerskov C, Kenborg L
Int J Cancer · 2026 Jun · PMID 42322221 · Publisher ↗
Population-based evidence on cancer survival in individuals with neurofibromatosis 1 (NF1) remains limited. We compared survival following a first neoplasm in individuals with NF1 to that of the general Danish population...
Population-based evidence on cancer survival in individuals with neurofibromatosis 1 (NF1) remains limited. We compared survival following a first neoplasm in individuals with NF1 to that of the general Danish population and stratified on age, sex, and potential survival-related factors, including cancer stage and comorbidity. Using the Danish Cancer Registry, we identified 428 individuals with NF1 and 392,885 without NF1, all diagnosed with a first neoplasm (1977-2022). We estimated survival using Kaplan-Meier methods, assessed neoplastic and nonneoplastic mortality, and evaluated prior inpatient disease burden in adults (aged 20-69 years) based on hospital diagnoses 10 years to 6 months before neoplasm diagnosis. Among children (aged 1-19 years), NF1 was overall associated with better 5-year survival (NF1: 87.3% [81.1%-93.5%], non-NF1: 78.7% [77.9%-79.6%]), due to better survival following central nervous system (CNS) neoplasms. In adults, 5-year survival was lower in NF1 compared to the general population (57.0% [51.3%-62.6%] vs. 69.2% [69.0%-69.3%]). NF1 adults more often presented with stage IV breast (17.2% vs. 6.3%) and gastrointestinal cancers (52.5% vs. 37.7%). Among adults with no prior inpatient diagnoses, 5-year survival was poorer in NF1 (60.1% [51.3%-68.9%] vs. 72.1% [71.9%-72.3%]). Five-year neoplastic mortality was higher in NF1 adults (39.4% [33.8%-45.0%] vs. 27.7% [27.6%-27.9%]). In conclusion, individuals with NF1, particularly adults, have poorer cancer survival than the general population. Differences in cancer type and stage at diagnosis contribute but do not fully explain the excess mortality, indicating that factors beyond general health status may play a role.
Longitudinal Associations Between Inflammation and Multi-Dimensional Fatigue up to 2 Years After Colorectal Cancer Diagnosis.
Bruijnzeels AEC, Mols F, Van Deun K … +1 more , Schoormans D
Int J Cancer · 2026 Jun · PMID 42322026 · Publisher ↗
Cancer-related fatigue (CRF) is a prevalent symptom among colorectal cancer (CRC) survivors. While inflammation is a proposed underlying mechanism, longitudinal evidence including pre-treatment assessments remains scarce...
Cancer-related fatigue (CRF) is a prevalent symptom among colorectal cancer (CRC) survivors. While inflammation is a proposed underlying mechanism, longitudinal evidence including pre-treatment assessments remains scarce. Within the population-based PROCORE study, newly diagnosed CRC patients provided blood samples and completed questionnaires at diagnosis (n = 411; 60.6% male; age = 67.0 years), 12- (n = 304), and 24-month follow-up (n = 252). Eleven inflammatory biomarkers (CRP, IFN-γ, IL-1α, IL-1β, IL-6, IL-8, IL-10, IL-17A, IL-22, sTNFRI, and sTNFRII) were assayed; CRF was measured with the Multidimensional Fatigue Inventory. Hybrid linear mixed models disentangled between- and within-subject associations, controlling for sociodemographic (e.g., age), clinical (e.g., cancer treatment), and lifestyle covariates (e.g., BMI), sleep quality, and pain. A normative age- and sex matched sample (n = 204; 52.5% male; age = 64.3 years) was included for comparison. Soluble TNF receptors (sTNFRI/II) were most robustly and positively associated with nearly all fatigue dimensions. CRP was positively associated with mental and physical fatigue; IL-8 positively associated with multiple domains including reduced motivation; and IFN-γ positively associated with general fatigue and reduced activity. Lower IL-1α was associated with more mental fatigue. Between-subject effects mirrored overall results; within-subject effects were more selective. Associations were most consistently observed for mental fatigue. In controls, less associations were significant; CRP was the most robust marker and positively associated with general fatigue, reduced activity, and reduced motivation. CRC survivors exhibited a broader, mostly TNF-α driven inflammatory signature of fatigue than controls. Findings highlight inflammation as a potential target underlying CRF, informing survivorship care strategies.
Can the Parallel or Tandem Combination of Questionnaire-Based Risk Assessment and Fecal Immunochemical Test Improve the Efficiency of Colorectal Cancer Screening?
Liu R, Ji J, Wei X … +3 more , Zheng C, Zhang N, Sun Q
Int J Cancer · 2026 Jun · PMID 42322011 · Publisher ↗
Colorectal cancer (CRC) screening reduces disease burden, but the comparative performance of various screening strategies remains unclear. We evaluated the performance of four screening strategies based on questionnaire-...
Colorectal cancer (CRC) screening reduces disease burden, but the comparative performance of various screening strategies remains unclear. We evaluated the performance of four screening strategies based on questionnaire-based risk assessment (QRA) and fecal immunochemical test (FIT), followed by colonoscopy. In this population-based study, 14,327 residents aged 40-74 years from 13 regions in Shandong Province, China, were invited to undergo QRA, FIT, and colonoscopy between January 2024 and December 2025. Based on test results, we constructed four strategies: QRA-only, FIT-only, parallel (QRA or FIT positive), and tandem (QRA and FIT positive) combinations. The detection rate of CRC and advanced adenoma (AA), number needed to scope (NNS), and cost per case detected were compared. In total, 4982, 1806, 5970, and 764 individuals were identified as high-risk for each strategy. The tandem strategy detected 33 CRCs (4.32%) and 199 AAs (26.03%), compared with 35 (0.71%) and 553 (11.22%) in the QRA-only strategy, 68 (3.77%) and 340 (18.86%) in the FIT-only strategy, and 70 (1.17%) and 694 (11.62%) in the parallel strategy. Across subgroups defined by older age, male, and early-stage disease, the tandem strategy consistently yielded higher detection rates. The NNS to detect one CRC was 141, 27, 86, and 24, and the corresponding costs per CRC detected were $9874.31, $2097.88, $7084.68, and $1700.71 for each strategy. The tandem strategy combining QRA and FIT demonstrated superior performance in CRC screening. In resource-constrained settings, tandem strategies that jointly integrate risk assessment and FIT may improve the allocation and utilization of screening resources.
Lynch Syndrome and Ethnicity: Disparities in Prevalence, Affected Genes, Cancer Spectrum and Screening.
Ealiwa N, Shtaya AA, Alamour W … +5 more , Cohen DL, Alamour O, Abu-Tailakh M, Khader M, Abu-Freha N
Int J Cancer · 2026 Jun · PMID 42318823 · Publisher ↗
Lynch Syndrome (LS) patients have a significantly increased risk for colorectal cancer (CRC), as well as extracolonic malignancies. This review aims to summarize published data on the prevalence of LS, affected genes, th...
Lynch Syndrome (LS) patients have a significantly increased risk for colorectal cancer (CRC), as well as extracolonic malignancies. This review aims to summarize published data on the prevalence of LS, affected genes, the cancer spectrum, and universal screening across different populations. We conducted a narrative review of English-language studies published in scientific databases addressing these key aspects of LS. The reported prevalence of LS among unselected CRC patients ranges from 0.7% to 4%, with a higher rate observed in selected high-risk patients. The overall prevalence of LS was reported to be 2.2% in a large meta-analysis. Among patients with endometrial cancer, the prevalence has been reported to reach 5.9% in Canadian patients. Notably, the prevalences of LS in both CRC and endometrial cancer show large variations across different geographic regions and ethnic groups. In most populations, the genes most frequently affected are path_MLH1 and path_MSH2. However, in certain regions, path_PMS2 mutations appear to be more common. This pattern has been observed in small cohorts from Arab countries, as well as in isolated studies from the United Kingdom and the United States. In addition, the cumulative cancer risk for CRC, endometrial, ovarian, and urothelial cancers varies widely in different populations. Studies involving unselected patients are more commonly conducted in European countries and the United States (US). In contrast, studies from other regions primarily included selected high-risk patients. In conclusion, the geographic and ethnic variations underscore the need for population-specific data and tailored screening strategies, with individualized genetic analysis and surveillance protocols.
Resource-Adapted Triage Strategies for Women Testing HPV Positive With Self-Collected Vaginal Samples in Cameroon.
Murtas M, Vassilakos P, Wisniak A … +9 more , Hu K, Arbyn M, Tankeu Happi GW, Abatsong E, Nsangou FMN, Tille JC, Saiji E, Kenfack B, Petignat P
Int J Cancer · 2026 Jun · PMID 42312659 · Publisher ↗
The World Health Organization (WHO) recommends HPV-DNA testing as the primary screening method for cervical cancer in low- and middle-income countries (LMICs), yet guidance on how to triage HPV-positive women remains lim...
The World Health Organization (WHO) recommends HPV-DNA testing as the primary screening method for cervical cancer in low- and middle-income countries (LMICs), yet guidance on how to triage HPV-positive women remains limited. The 2021 WHO guidelines for LMICs do not incorporate extended HPV genotyping, despite its potential to improve risk stratification and support scalable management strategies. This study evaluated screening strategies based on locally available resources for management of HPV-positive women. We retrospectively analyzed data from the 3T study (Test, Triage, and Treat), conducted between 2018 and 2022, which included HPV self-sampling and VIA triage among women aged 30-49 years. For all HPV-positive participants, HPV testing (stratified into five genotype-based risk groups), cytology, VIA, cervical-biopsy, and endocervical-brush histopathology were available. Thirty-five screening and triage strategies integrating HPV extended genotyping alone or in combination with VIA or cytology were assessed using CIN3+ risk as a guiding principle. Among 868 HPV-positive women, 9% had CIN3+ lesions. HPV types 31/33/35/52/58 were most prevalent, whereas HPV16 and HPV18/45 carried the highest CIN3+ risks. Strategies combining extended genotyping with cytology demonstrated the best balance of sensitivity and specificity. In settings without access to cytology or VIA, direct treatment of the eight highest-risk HPV types, 16/18/45/31/33/35/52/58, showed the best balance between sensitivity and specificity. When cytology or VIA was available, immediate treatment for HPV16 and reflex triage, cytology (treating ≥ ASCUS lesions), or VIA for HPV18/45/31/33/35/52/58 showed the best trade-off. The proposed screening strategies enable risk-adapted triage and guide management decisions based on available resources.
Limb Compression Therapy and Chemotherapy-Induced Peripheral Neuropathy in Women With Gynecologic Cancers: A Prospective Self-Controlled Study(NEURO-GLOVE Trial).
Başkurt K, Uyar GC, Yeşilbaş E … +9 more , Altunç FZ, Çevik DE, Melek İM, Eren Y, Öksüzoğlu ÖBÇ, Yücel KB, Di Meglio A, Ray-Coquard I, Sütcüoğlu O
Int J Cancer · 2026 Jun · PMID 42311202 · Publisher ↗
Chemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting toxicity of taxane-based chemotherapy with limited preventive options. We evaluated whether dual-site mechanical compression during paclitaxel infusion...
Chemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting toxicity of taxane-based chemotherapy with limited preventive options. We evaluated whether dual-site mechanical compression during paclitaxel infusion reduces CIPN in women with gynecologic cancers. In this prospective, intraindividual, self-controlled study, patients receiving carboplatin-paclitaxel underwent compression of the nondominant hand (two surgical gloves) and ipsilateral lower limb (Class II stocking), while contralateral limbs served as controls. CIPN was assessed using CTCAE v5.0 and EORTC QLQ-CIPN20 at baseline, Cycle 3, end of treatment (EOT), and 3- and 6-month follow-up. Among 76 patients (median age, 61 years), moderate-to-severe CIPN was observed less frequently in compression limbs than in control limbs at Cycle 3 (35.5% vs. 53.9%; p = 0.001), EOT (59.2% vs. 69.7%; p = 0.021), 3 months (28.9% vs. 52.6%; p = 0.015), and 6 months (20.3% vs. 33.8%; p = 0.002). Repeated-measures analyzes showed significant time-by-limb interactions for sensory (p = 0.003), lower-extremity sensory (p = 0.018), and motor domains (p = 0.041). Sensory CIPN20 scores were lower in compression limbs in the upper extremities from EOT onward (7.5 vs. 10.2; p < 0.001) and in the lower extremities at 3-month (8.7 vs. 10.7; p < 0.001) and 6-month follow-up (7.0 vs. 10.0; p < 0.001). EORTC QLQ-CIPN20 sensory scores identified grade ≥ 2 neuropathy with AUC values > 0.92 at all time points. Dual-site mechanical compression was associated with reduced incidence and persistence of CIPN. As a low-cost and scalable intervention, this strategy may improve treatment tolerability and survivorship outcomes. Trial Registration: ClinicalTrials.gov identifier: NCT07105553.
Clinical Implementation and Oncological Relevance of Molecular Profiling in Brain Metastases Patients-A Multicenter Retrospective Cohort Study.
Nikolaeva M, Bellomo J, Gönel M … +23 more , Stumpo V, Staartjes VE, Vasella F, Akeret K, Sagerer A, Zeitlberger AM, Wasilewski D, Krämer C, König S, Onken J, Juratli T, Köpp A, Reimann R, Czabanka M, Vajkoczy P, Eyüpoglu IY, Bozinov O, Weller M, Le Rhun E, Regli L, Serra C, Neidert MC, Voglis S
Int J Cancer · 2026 Jun · PMID 42311197 · Publisher ↗
Brain metastases (BM) require a multidisciplinary treatment approach combining surgery, radiotherapy, and systemic therapy. While current guidelines recommend the analysis of established cancer driver genes in BM tissue,...
Brain metastases (BM) require a multidisciplinary treatment approach combining surgery, radiotherapy, and systemic therapy. While current guidelines recommend the analysis of established cancer driver genes in BM tissue, little is known about its real-life implementation and relevance on oncological treatment strategies. This retrospective multicenter study includes patients with BM from melanoma, lung and breast cancer operated between 2010 and 2022. Clinical records were evaluated for BM molecular analyses of predefined cancer drivers and their discordance to extracranial tumor sites, that is, ALK, BRAF, EGFR, KRAS, NTRK for lung, HER2, estrogen/progesterone receptor, BRCA1/2 for breast cancer and BRAF, KIT, NRAS among others for melanoma. Adjustment of systemic therapies based on BM molecular profiles was analyzed. Among 1431 BMs screened for availability of molecular analysis, molecular profiling was performed at least partially in 723 BMs (51%). In cases with matched extracranial tumor samples (n = 276), discordant alterations were found in 18% of lung, 4.7% of melanoma and 45% of breast cancer BMs. Molecular BM analyses informed systemic therapy adjustments in 13%-27% of patients depending on the primary tumor. Overall survival was significantly better in patients who underwent BM profiling, especially when operated in recensst years (median 19.3 vs. 9.9 months; p < 0.0001) and in patients with breast cancer who had a change in systemic therapies upon BM profiling (p = 0.0085). In conclusion, molecular profiling of BM allows selecting available treatment options for a substantial subset of patients. This study underscores the need for more systematic molecular testing in BM patients to guide systemic treatment decisions.
Total Neoadjuvant Treatment for Esophageal Adenocarcinoma With Oligometastases: TNT-OES-1 Trial.
van der Zijden CJ, Huizer TJ, Eyck BM … +10 more , van der Gaast A, van Doorn L, Homs MYV, van Lanschot JJB, Nuyttens JJME, Oudijk L, Spaander MCW, Wijnhoven BPL, Mostert B, Lagarde SM
Int J Cancer · 2026 Jun · PMID 42311191 · Publisher ↗
Chemotherapy (FLOT) and chemoradiotherapy (CROSS) are both effective as neoadjuvant regimens for esophageal/junctional cancer. Total Neoadjuvant Therapy (TNT) aims to increase efficacy by combining chemotherapy with chem...
Chemotherapy (FLOT) and chemoradiotherapy (CROSS) are both effective as neoadjuvant regimens for esophageal/junctional cancer. Total Neoadjuvant Therapy (TNT) aims to increase efficacy by combining chemotherapy with chemoradiotherapy. This study aimed to evaluate the feasibility and safety of TNT FLOT-CROSS. Patients with histologically proven esophageal/junctional adenocarcinoma with oligometastases (maximum four lesions in maximum two organs) were included. Treatment consisted of four cycles of FLOT followed by response evaluation (CT-scan). Patients without disease progression proceeded to CROSS, followed by response evaluation (CT-scan, endoscopy with biopsies and endoscopic ultrasonography with fine-needle aspiration on indication). Primary endpoint was the safety and tolerability of TNT FLOT-CROSS. Secondary endpoints included progression-free survival (PFS), disease control rate (DCR), quality of life (QoL) using QLQ-C30 and QLQ-OG25, toxicity and the proportion of patients proceeding to local therapy. Twenty patients were included of whom 16 (80%) had a single metastatic lesion. Median follow-up was 47.9 months (95% CI 32.8-63.1). Fifteen patients (75%) completed TNT FLOT-CROSS. FLOT came with manageable, expected toxicity, and all patients without progression were able to start and complete CROSS. No grade 3-5 toxicities occurred during CROSS. After TNT FLOT-CROSS, two patients underwent surgery. The 1- and 2-year PFS were 40% and 13%, respectively. Three months after TNT FLOT-CROSS completion, DCR was 55%. Dysphagia scores significantly decreased over time, while fatigue significantly increased. Sequencing TNT FLOT-CROSS in patients with oligometastatic esophageal adenocarcinoma is feasible and comes with manageable toxicity and promising efficacy, with a 1-year progression free survival of 40%. Trial Registration: Dutch trial register, NL9269.
Availability of Stage Information From Cancer Registries Providing Data to the European Cancer Information System for Six Selected Cancers.
Bosetti C, Visser O, Van Eycken L … +8 more , Pettersson D, Bartnicka JJ, Dyba T, Randi G, Flego M, Carvalho RN, Bettio M, ECIS Working Group
Int J Cancer · 2026 Jun · PMID 42298920 · Publisher ↗
Cancer stage at diagnosis is crucial to guide clinical decision making and support cancer surveillance, enabling meaningful international comparisons of epidemiological cancer indicators and evaluation of cancer control...
Cancer stage at diagnosis is crucial to guide clinical decision making and support cancer surveillance, enabling meaningful international comparisons of epidemiological cancer indicators and evaluation of cancer control policies. The collection of stage information by population-based cancer registries (PBCRs) is therefore essential, yet a comprehensive overview of stage availability across European PBCRs has been lacking. We analyzed the availability and completeness of stage at diagnosis reported by PBCRs affiliated with the European Network of Cancer Registries (ENCR) in the 2022 European Cancer Information System (ECIS) data call. The assessment focused on six major cancers, that is, breast, cervix, colorectum, gastric, lung, and prostate. Between 1990 and 2022, 67 (78%) PBCRs from 18 countries-out of 86 registries submitting incidence data to ECIS by September 2025-provided information on stage. Sixty-five (97%) used the Tumor-Nodes-Metastasis (TNM) system, although four coded a substantial proportion of cases using other staging systems. Many countries showed improvements over time in reporting TNM stage. In the period 2017-2019, in most countries more than 80% of breast, cervical, colorectal, and lung cancer cases had TNM information, while gastric and prostate cancers exceeded 70%. Nevertheless, a few countries reported TNM stage for less than half of their cases. Overall, stage at diagnosis is available for a large proportion of cancer cases in Europe, demonstrating the commitment of PBCRs to high-quality data collection. However, important gaps persist in some countries. Continued cooperation between the ENCR and ECIS is needed to support harmonized stage reporting across European registries.
Pancreatic Cancer Early Detection Biomarkers for High-Risk Individuals: Insights From the PRECEDE Consortium.
Worthington C, Raitses-Gurevich M, Innamorati G … +15 more , Hart PA, Wilkie TM, Tau N, Brin D, Yablecovitch D, Laish I, Keith D, Giles K, Permuth JB, Simeone DM, Zogopoulos G, Brand RE, Graff JJ, Earl J, PRECEDE Consortium
Int J Cancer · 2026 Jun · PMID 42298760 · Publisher ↗
Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest cancers due to its asymptomatic progression, late-stage diagnosis, and treatment resistance. Efforts in early detection have centered on identifying im...
Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest cancers due to its asymptomatic progression, late-stage diagnosis, and treatment resistance. Efforts in early detection have centered on identifying imaging features and liquid biopsy biomarkers capable of detecting PDAC and its high-grade precursors before clinical symptoms arise in patients at elevated risk of PDAC development. Classical imaging-based surveillance strategies, aligned with current guidelines, form the foundation of screening high-risk individuals, while organ-specific fluid analyses-such as cyst fluid and pancreatic juice-offer promising complementary tools with enhanced specificity. Recent advances in radiomics, liquid biopsy, microbiome, and multi-omics profiling are expanding the frontier of early detection. Despite advances, significant challenges persist. Precursor lesions are difficult to non-invasively diagnose; are not radiologically or endosonographically visible, or cannot be definitively graded prior to resection. Though biomarkers show promise for early detection, they present unique challenges: early-stage neoplasias release low levels of many biomarkers and thresholds for these biomarkers that define malignant transformation-and thus guide surgical intervention-remain poorly established. Multi-institutional initiatives like the Pancreatic Cancer Early Detection consortium (PRECEDE) are critical to bridging discovery and clinical translation. Our international cohort study of high-risk individuals was designed to discover and validate diagnostic biomarkers according to the PROBE study design. Continued collaboration, technological integration, and patient-centered approaches are essential to transform early detection research into tangible survival benefits for those at risk of PDAC.
Systemic Lipid Peroxidation and Colorectal Cancer Risk: A Time-Varying Relationship.
Yang G, Milne GL, Nogueira MS … +6 more , Gao YT, Lan Q, Yi H, Shu XO, Zheng W, Chen Q
Int J Cancer · 2026 Jun · PMID 42298759 · Publisher ↗
Despite widespread interest, large randomized controlled trials have failed to demonstrate chemopreventive benefits of antioxidant supplementation, raising concerns about its efficacy and safety. Building on our prior ob...
Despite widespread interest, large randomized controlled trials have failed to demonstrate chemopreventive benefits of antioxidant supplementation, raising concerns about its efficacy and safety. Building on our prior observation of a time-dependent inverse association between systemic oxidative stress (OxS), assessed using nucleic acid oxidation biomarkers, and colorectal cancer (CRC) risk, we extended this investigation to systemic lipid peroxidation and evaluated whether a composite OxS index incorporating DNA, RNA, and lipid markers improves risk characterization. We conducted a nested case-control study within two Shanghai cohorts (1938 CRC cases) and replicated findings in a US cohort (285 cases). Systemic lipid peroxidation was assessed using urinary F-isoprostanes (F-IsoPs), quantified by UPLC-MS/MS. Conditional logistic regression estimated odds ratios (ORs) for CRC risk. Lower levels of 5-F-IsoP, a major F-IsoP isomer generated exclusively via free radical oxidation, were associated with increased CRC risk in both the primary and replication cohorts. Time-dependent associations were evaluated in the Shanghai cohorts. For CRC diagnosed within 5 years following enrollment, multivariable-adjusted ORs (95% CI) at the 10th and 90th percentiles of 5-F-IsoP levels, relative to the median, were 1.57 (1.26-1.96) and 0.61 (0.42-0.89), respectively, indicating a 2.2-fold difference in risk. The composite OxS index showed an even stronger association (3.9-fold difference). No significant associations were observed for diagnoses beyond 5 years. This study provides new evidence that systemic OxS is inversely and time-dependently associated with CRC risk during later stages of disease development, raising concerns that lowering systemic OxS via high-dose antioxidant supplementation potentially carry unintended risks for high-risk individuals.
TRIM24 in Human Cancers: A Dual-Function Oncoprotein, Regulatory Mechanisms, and Emerging Therapeutic Strategies.
Zeng W, Xu K, Wang Y … +7 more , Shou Y, Xiong H, Liang L, Xu H, Liu R, Zhang H, Lu Y
Int J Cancer · 2026 Jun · PMID 42290584 · Publisher ↗
The tripartite motif-containing protein 24 (TRIM24) functions as a pivotal epigenetic scaffold and E3 ubiquitin ligase, orchestrating tumorigenesis through context-dependent dual roles. While frequently amplified in canc...
The tripartite motif-containing protein 24 (TRIM24) functions as a pivotal epigenetic scaffold and E3 ubiquitin ligase, orchestrating tumorigenesis through context-dependent dual roles. While frequently amplified in cancers such as prostate and breast carcinoma-where it drives oncogenesis via Wnt/β-catenin and PI3K/AKT pathway activation-emerging evidence positions TRIM24 as a tumor suppressor in specific contexts, modulating retinoic acid signaling and macrophage polarization. This dichotomy is governed by intricate post-translational modifications (PTMs), including phosphorylation-dependent nucleocytoplasmic shuttling and SUMOylation, which dictate substrate specificity for targets ranging from p53 to VHL. Furthermore, TRIM24 operates within a complex non-coding RNA network (e.g., miRNA-511, lncRNA NCK1-AS1) that fine-tunes its oncogenic output. Clinically, aberrant TRIM24 expression correlates with poor prognosis and therapeutic resistance across multiple malignancies. Mechanistically, its unique PHD-Bromo dual-domain structure confers specific recognition of the noncanonical H3K4me0/H3K23ac histone signature, presenting a compelling therapeutic target. Current strategies, including PROTAC degraders and allosteric inhibitors targeting its bromodomain or downstream effectors (e.g., DNA-PKcs, AURKB), demonstrate significant preclinical efficacy. This review synthesizes the molecular circuitry of TRIM24, elucidates the determinants of its functional switch, and evaluates emerging precision medicine approaches to overcome resistance in TRIM24-addicted tumors.
Correction to "FHL Expression by Cancer-Associated Fibroblasts Promotes Metastasis and Angiogenesis in Lung Adenocarcinoma".
Int J Cancer · 2026 Jun · PMID 42290546 · Publisher ↗
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