Oesophageal squamous cell carcinoma (OSCC) accounts for more than 85% of the global burden of oesophageal cancer, resulting in 500 000 deaths annually. In the UK, over two-thirds of OSCC cases are diagnosed at an advanced stage, with a 5-year overall survival of less than 20%. Breath-based triage tests are feasible, acceptable and show proof of concept for earlier cancer detection.

The Volatile Organic Compounds as Breath Biomarkers in Squamous Oesophageal Neoplasms (ViSON) study is a multicentre case-control study powered to estimate breath test performance with 90% sensitivity and 80% specificity. A total of 518 participants (259 with OSCC and 259 non-cancer controls) will be recruited via a network of participating National Health Service trusts. Participants will provide exhaled breath samples, which will be stored on Thermal Desorption tubes and transported to the central laboratory for processing and analysis using gas chromatography-mass spectrometry. A clinical prediction model will be developed using logistic regression with cross-validation and bootstrap methods to mitigate overfitting. Model performance will be evaluated using discrimination, calibration and accuracy. Decision curve analysis will assess clinical utility.

The ViSON study received ethical approval from the London - Riverside Research Ethics Committee (23/PR/1300) from the Health Research Authority (HRA) and the Health and Care Research Wales (HCRW) to conduct study procedures in England and Wales. A Scotland-wide review was approved on 24 January 2024. The results of the study will be presented at national and international conferences, and a lay summary will be developed with the patient and public involvement representatives and shared using the online website, social media accounts and charity newsletters.

NCT06169163.

To evaluate engagement and weight loss with a 12-month total diet replacement (TDR) programme in women with increased risk of breast and endometrial cancer, living with obesity.

Prospective cohort study.

Secondary care.

47 premenopausal women living with obesity.

12-month programme including a 12-week TDR phase with biopsies of the breast and endometrium, before and after, followed by 4 weeks of diet reintroduction and a weight maintenance/continued weight loss phase (weeks 17-52).

This paper reports retention and adherence to the programme, weight loss, changes in mental well-being, quality of life (QoL), weight loss self-efficacy, physical activity and fidelity of delivery of the programme.

37 women (79%) completed the whole programme. Completers and those who withdrew, respectively, had a mean (SD) age of 41.4 years (5.7) vs 38.1 (5.8) and baseline body mass index of 36.2 (4.9) kg/m² vs 40.0 (7.9) kg/m² and 76% vs 90% had children 18 or younger living at home. Median (IQR) weight was reduced at all time points; -10.8 kg (-13.8, -7.2) at 3 months, -11.5 kg (-15, -7.6) at 6 months, -11.0 kg (-16.4, -7.8) at 9 months and -8.4 kg (-13.9, -3.7) at 12 months. Across the 12-month programme, the median (IQR) contacts with the study dietitians per participant was 28 (25, 33) and median contact hours were 7.6 (6.6, 10.6). 68% received psychological support. QOL improved; OWL-QOL (Obesity and Weight Loss)-17 (-24.8, -7.8) and EQ5D 1 (0, 2), with reductions in binge eating scores -4 (-6.5, -0.8) but no changes in mental health or physical activity scales.

TDR could be a weight loss programme for women at increased risk of breast and endometrial cancers related to obesity. Future controlled trials with extended follow-up are required before recommending routine implementation of TDR in high-risk clinics.

ISRCTN15358157.

Focus groups involving US women aged 40-49 were conducted to identify women's attitudes towards the 2024 United States Preventive Services Task Force (USPSTF) mammography guideline, particularly the change in emphasis away from informed choice. Focus groups explored what information women feel they need to receive about screening benefits and harms prior to getting a mammogram.

Seven focus groups of 4-6 women were conducted 3-4 months following the USPSTF guideline announcement.

Participants were recruited from two healthcare systems in the USA and participated in focus groups via Zoom.

Women aged 40-49 with no history of breast cancer. Purposive sampling stratified by race, education and screening preferences.

Participants had previously received a Decision Aid as part of a parent study informing them of the pre-2024 USPSTF guideline and mammography mortality benefit, false positives and overdiagnosis.

Rapid qualitative analysis focused on summarising groups' answers to questions posed to the focus groups.

Groups were generally positive towards lowering the screening age to 40 but felt that screening frequency should be tailored to personal cancer risk. They strongly emphasised the importance of being informed about both the benefits and harms of mammography, despite the reduced emphasis on informed choice, and stressed a desire for transparency and autonomy.

US women were positive about the recommendation to screen at age 40 but wanted screening frequency to be tailored to their cancer risk. They valued being fully informed of both screening benefits and harms and expected that all women should be fully informed.

NCT05838417.

This study aimed to explore the developmental experiences and nursing needs of female patients diagnosed with Peutz-Jeghers syndrome (PJS) during childhood, thereby providing references for developing targeted nursing interventions.

Using purposive sampling, face-to-face semistructured interviews were conducted with female patients diagnosed with PJS in childhood. Data were gathered and examined using directed content analysis based on phenomenological research principles.

The study was conducted in Shanghai, China.

In total, 35 female patients diagnosed with PJS in childhood were interviewed.

Three themes and nine subthemes emerged: microsystem (self-perception and social barriers, challenges related to marriage and childbearing, physiological and psychological distress and treatment adherence pressure), mesosystem (inadequate family communication and support, as well as social isolation) and macrosystem (uneven distribution of medical resources, weak social support networks, as well as inadequate policy and insurance coverage).

Female patients with childhood-onset PJS face diverse and complex challenges within their social environments. Healthcare professionals should recognise the physical and psychological impacts of the illness, provide appropriate interventions to address patients' needs and help maintain ecosystem stability.

Infectious agents are an important preventable cause of cancer globally. To inform prevention efforts, we provide a comprehensive picture of cancer burden attributable to infections, including newly established, carcinogenic infectious agents and latest global cancer incidence estimates.

In this worldwide incidence analysis, we used data from the Global Cancer Observatory's Cancer Today (GLOBOCAN) database of cancer incidence in 2024 to estimate population-attributable fractions (PAFs), absolute numbers, and age-standardised incidence rates (ASIRs) of new cancer cases attributable to 12 infectious agents classified as Group 1 carcinogens by the IARC Monographs Programme: Helicobacter pylori, human papillomavirus (HPV), hepatitis B (HBV) and hepatitis C viruses (HCV), Epstein-Barr virus (EBV), Kaposi's sarcoma-associated herpesvirus, Schistosoma haematobium, human T-cell lymphotropic virus, Opisthorchis viverrini, Clonorchis sinensis, Merkel cell polyomavirus, and HIV. Estimates stratified by sex, country, and age group were aggregated by UN geographical subregion and World Bank income group.

An estimated 2·3 million new cancer cases were attributable to infections globally in 2024, which is equivalent to 12% of all cancer cases. The largest number of cases was attributable to H pylori (n=760 000, PAF 4%), followed by HPV (n=750 000, 4%), HBV (n=360 000, 2%), EBV (n=260 000, 1%), and HCV (n=160 000, <1%). The largest burden of infection-attributable cancer was in eastern Asia, with 990 000 cases (42% of the global total, ASIR 31·9 per 100 000 cases). ASIRs were also higher than the global average (22·7) in sub-Saharan Africa (28·5), central and eastern Europe (24·3), and southeastern Asia (23·1). Focused analysis of EBV-attributable cancers revealed regional variation in the distribution of cancer types.

Our findings highlight the importance of infection control to achieve cancer prevention. Scientifically proven, but often underused, approaches include HPV and HBV vaccination; testing and treatment of HIV, H pylori, HBV, and HCV; safe injection practices; access to condoms and pre-exposure prophylaxis to prevent HIV transmission; and screening of precancerous lesions for HPV-driven cervical and anal cancer. Our findings also inform the investment cases for research and development for new prevention tools, most notably for EBV.

None.

Head and neck cancer (HNC) outcomes may vary with facility specialization. Japan operates a nationwide board certification system that accredits training facilities based on case volume, multidisciplinary capacity, and specialist staffing. We examined whether treatment at certified facilities is associated with survival and assessed geographic variation in access to such facilities.

In this nationwide retrospective cohort study using the hospital-based cancer registry, we included 75,196 patients with primary invasive HNC diagnosed between 2012 and 2015 who received first-course treatment at board-certified (n = 48,674; 119 facilities) or non-certified (n = 26,522; 386 facilities) facilities. The primary outcome was 5-year overall survival, analysed using multilevel survival models with facility-level random effects adjusted for age and sex, stratified by stage (I-II vs III-IV) and subsite.

Board-certified facilities treated a higher proportion of patients with stage III-IV disease (55.2% vs 45.1%). For stage I-II disease, the 5-year survival was similar (76.7% vs 75.3%; adjusted hazard ratio [aHR], 0.99; 95% CI, 0.93-1.04). For stage III-IV disease, survival was higher at certified facilities (50.7% vs 44.9%; aHR, 0.86; 95% CI, 0.82-0.90). Stage-dependent associations were broadly consistent across subsites. The proportion of residents treated at certified facilities ranged from 9.7% to 91.9% across prefectures.

Treatment at board-certified facilities was associated with better survival for advanced but not early-stage HNC, suggesting specialization matters most for complex multimodality care. Substantial geographic variation in access represents a target for policy efforts aligning quality with equity.

Follicular helper T (T_FH) cells play a crucial role in adaptive humoral immunity. They provide help to B cells in the germinal centers (GCs), driving the affinity maturation of antigen-specific antibodies and class switch recombination. T_FH cells possess profound heterogeneity in spatial distribution (e.g., GC-T_FH, follicular mantle-T_FH, circulating T_FH, peripheral T_FH) and phenotypic characteristics (e.g., T_FH1, T_FH2, T_FH17), which enable T_FH cells to respond to diverse immune challenges. This review summarizes the recent progress, including our data, on the T_FH regulatory network driven by B-cell lymphoma 6 (Bcl-6) and cellular musculoaponeurotic fibrosarcoma oncogene homolog (c-Maf), and the contradictory roles exhibited by different T_FH subsets under disparate pathological conditions such as viral infections, autoimmune diseases, and cancer. Integrating multiple T_FH subsets into a systematic framework can provide a new perspective for understanding humoral immune regulation and developing new targeted therapies.

Myeloproliferative neoplasms (MPNs) are clonal hematologic malignancies characterized by the overproduction of mature myeloid lineage cells. Although JAK2 inhibitors, such as ruxolitinib, can alleviate constitutional symptoms, they typically fail to eradicate malignant clones or reverse bone marrow fibrosis. Moreover, treatment failure and drug intolerance often limit their long-term use. Recent studies have identified PIM1 kinase as an important mediator of MPN pathogenesis. PIM1 expression is upregulated in MPN hematopoietic progenitors, which may contribute to aberrant proliferation and disease progression by regulating key downstream effectors, including mTORC1, BAD, MYC, HIF-1α, and TGF-β. Notably, PIM1 contributes to JAK2 inhibitor-persistent cell growth, and its inhibition restores ruxolitinib sensitivity in JAK2 mutant cells. Preclinical studies using genetic ablation and pharmacological inhibition of PIM1 have shown significant attenuation of the myelofibrosis phenotype in mouse models, providing a strong rationale for targeting this kinase. PIM kinase inhibitors are currently being evaluated in clinical trials for patients with myelofibrosis. This review summarizes the current understanding of PIM1 biology in the context of MPNs, details the molecular mechanisms underlying its pathogenic contributions, and evaluates the translational potential of PIM1-targeted therapies for MPNs.

Clonal monocytosis of undetermined significance (CMUS) and clonal cytopenia with monocytosis of undetermined significance (CCMUS) are recently defined precursor states, with unclear progression rates to myeloid neoplasms (MN), including chronic myelomonocytic leukemia (CMML). We evaluated a cohort of 958 patients with sustained monocytosis ( ≥ 0.5 ×10⁹/L, ≥10%) and stringently excluded MN. Among 958 patients, 74 met criteria for CMUS (n = 10) and CCMUS (n = 64), respectively. These patients were compared with a cohort with oligo monocytic-CMML (OM-CMML; n = 47). CMUS patients were younger (median age: 63 years), whereas CCMUS demonstrated lower BM blast %, in comparison to OM-CMML (median blast %: 1 vs. 2). OM-CMML was enriched for TET2 (60% vs. 32%, p = 0.012), ASXL1 (40% vs. 9%, p < 0.001), and SRSF2 (45% vs. 8%, p < 0.001) mutations, while CMUS/CCMUS had higher rates of DNMT3A (36% vs. 9%, p < 0.001) and PPM1D (12% vs. 0, p = 0.029) mutations. Mutation burden and VAF for most mutations (except SRSF2) were significantly higher in OM-CMML. DNMT3A mutations in CMUS/CCMUS often involved the methyltransferase (MT) domain, and MT domain mutations and co-mutations were associated with progression of CCMUS to CMML. With a median follow-up of 31 months, there were no progression events in CMUS patients, while 13% of CCMUS patients progressed to MN, mainly CMML (7/8). Median OS was inferior in OM-CMML (71 months) compared to CMUS/CCMUS (not reached), p < 0.001. Our findings demonstrate that CMUS and CCMUS represent biologically distinct clonal states with variable progression risk and highlight the importance of integrating morphologic and genomic data to refine classification.

Melanoma inhibitor of apoptosis protein (ML-IAP) is an IAP family member involved in tumour cell survival and a potential target in ML-IAP-expressing leukaemia. Here, 59 319 tetrapeptides were screened against ML-IAP by molecular docking, and four top-ranked peptides were selected. Microscale thermophoresis confirmed binding of peptides 1-4 to ML-IAP, with peptide-1 showing the lowest K_d value and a lower K_d value than the Smac peptide. Structure-activity relationship (SAR) analysis indicated that peptide-1 had more favourable ML-IAP recognition features. A molecular dynamics simulation, molecular mechanics/Poisson-Boltzmann surface area (MM/PBSA) calculations and free-energy landscape analysis supported the relative conformational stability of the ML-IAP-peptide-1 complex. MTT assays showed that peptide-1 inhibited MOLT-4, MOLM-13, and MV-4-11 cell proliferation, with limited inhibitory activity against HS-27A cells. ML-IAP knockdown reduced peptide-1 activity, while peptide-1 increased the cleaved/total caspase-3 ratio and altered Bax and Bcl-2 mRNA expression. These results suggest that peptide-1 may represent an ML-IAP-targeting peptide with antiproliferative activity in leukaemia cells.