Importance:Lung cancer (LC) remains the leading cause of cancer-related mortality worldwide, with tobacco smoking being the primary risk factor. However, the long-term LC risk among individuals with negative low-dose computed tomography (LDCT) findings and the role of tobacco smoking in risk stratification remain poorly understood, limiting evidence-based guidance for subsequent screening intervals. Objective:To evaluate the association of tobacco smoking with long-term LC risk after a negative baseline LDCT finding and to inform optimized screening strategies. Design, Setting, and Participants:This population-based, prospective cohort study was conducted under the Cancer Screening Program in Urban China. Individuals aged 40 to 74 years with negative baseline LDCT findings (October 1, 2013, to December 31, 2021) were included, with follow-up until December 2023. All participants were monitored for LC incidence. Exposures:Self-reported smoking status, pack-years, and time since quitting. Main Outcomes and Measures:The primary outcome was LC incidence, analyzed using Kaplan-Meier methods and multivariable Cox proportional hazards regression models. The association between smoking exposure and LC risk was assessed, with time-stratified analyses and dose-response associations. Results:Among 30 565 participants (14 761 never smokers and 15 804 smokers; mean [SD] age, 57.1 [7.7] years; 15 693 [51.3%] female), 76 LC cases occurred during 139 011.51 person-years (crude incidence rate, 54.67 of 100 000 person-years). Smokers had higher LC risk than never smokers (adjusted hazard ratio [AHR], 2.73; 95% CI, 1.49-5.01), driven by those with a smoking history of 20 pack-years or more (eg, ≥30 pack-years: AHR, 3.22; 95% CI, 1.85-5.58). There was no elevated risk at 2 years (AHR, 2.07; 95% CI, 0.91-4.69), but risk was significantly increased at 3 years (AHR, 2.54; 95% CI, 1.19-5.41) and onward. A nonlinear dose-response association was found between pack-years and LC risk, with risk surpassing clinically relevant thresholds at approximately 20 pack-years (eg, 20 to <30 pack-years: AHR, 2.48; 95% CI, 1.14-5.40). Females exhibited higher susceptibility than males at comparable exposure (≥30 pack-years: AHR, 5.78 [95% CI,1.87-17.83] for females vs 1.36 [95% CI, 0.18-10.39] for males). Significant risk was seen in those aged 50 to 54 years (≥30 pack-years) and 55 to 74 years (≥20 pack-years). Short-term cessation (<15 years) was not significantly associated with reduced LC risk. Conclusions and Relevance:In this cohort study, smokers with negative baseline LDCT findings exhibited a substantially elevated long-term LC risk, which became significant only after 2 years after screening. These findings suggest support for extending the initial screening interval and implementing personalized long-term monitoring based on smoking history.

Chronic alcohol consumption is an established risk factor for esophageal squamous cell carcinoma (ESCC). Elucidating the underlying mechanisms linking metabolic stress to esophageal carcinogenesis could help identify prevention and treatment strategies. Through a transancestry meta-analysis encompassing more than 200,000 individuals from East Asia, we identified a germline variant (rs1051921 C>T) at the MLXIPL locus [encoding carbohydrate-responsive element-binding protein (ChREBP)] that markedly elevated ESCC risk among alcohol drinkers. Functionally, the risk allele facilitated N6-methyladenosine (m6A) modification of ChREBP transcripts, enhancing their stability through recognition by the m6A reader YTHDF1. Alcohol further potentiated this regulatory axis by promoting ACSS2-mediated conversion of acetate into acetyl-CoA and increasing H3K27ac enrichment at the promoters of key m6A regulators. Increased ChREBP expression activated the transcription factor ATF3, which triggered endoplasmic reticulum stress and epithelial-mesenchymal transition, thereby conferring anoikis resistance. In parallel, ATF3 promoted an immunosuppressive tumor microenvironment through the upregulation of PD-L1 and VEGFA, leading to the exclusion of CD8+ T cells and the expansion of granulocytic myeloid-derived suppressor cells. In vivo intervention via ATF3 knockdown, anti-PD-L1 treatment, or pharmacologic perturbation of ChREBP-related metabolism with metformin or an ACSS2 inhibitor significantly suppressed ESCC progression and restored intratumoral CD8+ T-cell infiltration. These findings establish ChREBP as an alcohol-sensitive metabolic-epitranscriptomic switch that integrates genetic susceptibility with immune evasion to drive esophageal carcinogenesis. SIGNIFICANCE:Alcohol-responsive m6A-ChREBP signaling links genetic susceptibility to metabolic stress and immune evasion in esophageal cancer, revealing actionable targets for risk stratification, prevention, and immunometabolic intervention in high-risk drinkers.

Cardiovascular-kidney-metabolic (CKM) syndrome has been proposed, yet its utility for cancer risk stratification and behavior modification remains unclear. The study included 227,330 cancer-free participants from UK Biobank. CKM stages were defined using the American Heart Association (AHA) criteria, and lifestyle factors included smoking, alcohol consumption, physical activity, and diet. The hazard ratios (HRs) and lifetime risks of cancer were estimated using the Cox model and Fine and Gray's model, respectively. During a median follow-up of 11.46-13.65 years, 24,916 cancer cases and 7791 deaths were identified. Risks of cancer incidence and mortality increased progressively with advancing CKM stages (P trend < 0.001), with HRs (95% CIs) of 1.23 (1.15-1.30), and 1.58 (1.41-1.78) for stage 4. Compared with participants with unfavorable lifestyle, those with favorable lifestyle were associated with decreased risks across stages 0-4, with risk reductions of 14%-24% for cancer incidence, and 22%-40% for cancer mortality. Joint analyses showed that the increased cancer risks associated with CKM stages were eliminated or attenuated by adopting favorable lifestyle, particularly in stages 1-2. Participants in stage 4/unfavorable lifestyle had the highest risks of cancer incidence and mortality, with HRs (95% CI) of 1.54 (1.39-1.70) and 2.43 (1.97-2.99), and cumulative risks by age 80 of 34.77% and 11.65%, respectively. Furthermore, CKM stage 4/unfavorable lifestyle was associated with higher incidence of breast, colorectal, lung, kidney, pancreas, bladder, head and neck, esophagus, and liver cancers. These findings support the potential utility of CKM stages for cancer risk stratification and highlight the importance of lifestyle intervention.

Deciphering the composition of the tumor microenvironment (TME) is critical for understanding tumorigenesis and to design immunotherapies. In the present study, we mapped genetic effects on cell-type proportions using single-cell and bulk RNA sequencing data, identifying 3,494 immunity quantitative trait loci (immunQTLs) across 23 cancer types from The Cancer Genome Atlas. Functional annotation revealed regulatory potential and we further assigned 1,668 genes that regulate TME composition. We constructed a combined immunQTL map by integrating data from European and Chinese colorectal cancer (CRC) samples. A polygenic risk score that incorporates these immunQTLs and hits on a genome-wide association study outperformed in CRC risk stratification within 447,495 multiethnic individuals. Using large-scale population cohorts, we identified that the immunQTL rs1360948 is associated with CRC risk and prognosis. Mechanistically, the rs1360948-G-allele increases CCL2 expression, recruiting regulatory T cells that can exert immunosuppressive effects on CRC progression. Blocking the CCL2-CCR2 axis enhanced anti-programmed cell death protein 1 ligand therapy. Finally, we have established a database (CancerlmmunityQTL2) to serve the research community and advance our understanding of immunogenomic interactions in cancer pathogenesis.

ABSTRACT Pancreatic cancer is one of the most lethal malignancies. Genome‐wide association studies (GWAS) identify multiple susceptibility loci, but most map to noncoding regions, leaving variant‐to‐gene links unresolved. In this study, a genome‐wide regulatory map is constructed using expression quantitative trait loci (eQTL) analysis of 482 pancreatic tissues, and integrated with a GWAS meta‐analysis to prioritize causal variants. A total of 82 significant variants and 15 target genes for pancreatic cancer risk are identified, with enrichment in cancer‐related pathways. The variant rs11102484 is validated in an independent cohort of 569 cases and 2691 controls. The combined analysis of 5699 cases and 8467 controls confirms that the G allele of rs11102484 significantly reduces pancreatic cancer risk (odds ratio = 0.85, 95% confidence interval = 0.80–0.90, P = 4.83 × 10−8). Functional assays demonstrate that the G allele impairs ZNF263 binding at rs11102484, thereby weakening a long‐range silencer‐promoter interaction and increasing ST7L expression. Elevated ST7L dampens AKT/β‐catenin signaling and suppresses pancreatic cancer cell proliferation, consistent with the protective association. Overall, this study implicates functional genes in pancreatic cancer risk and characterizes a regulatory variant that modulates ST7L expression, advancing the interpretation of GWAS findings and understanding of pancreatic cancer biology.

Tailored cervical cancer screening strategies are essential, particularly in resource-limited settings. This study aimed to assess the genotype-specific impact of high-risk human papillomavirus (HR-HPV) infections on cervical cytological progression over a 3-year interval among Chinese women, thereby providing evidence for more precise and individualized screening approaches. A multicenter cohort was established in 2017 across three Chinese provinces. Participants underwent baseline HPV genotyping and cytological examination, with genotyping for five high-risk types (HPV16, 18, 33, 52, and 58), and follow-up evaluations conducted from 2018 to 2020. Cytological progression was defined as a transition from normal cytology (negative for intraepithelial lesion or malignancy, NILM) at baseline to low-grade squamous intraepithelial lesion (LSIL) or worse at the final follow-up. A total of 7240 women were included to evaluate the cytological progression. The overall progression rate was 0.7%, with a notably higher rate among HR-HPV-positive women (2.1%) compared to HR-HPV-negative women (0.5%). Specifically, HPV16, HPV52, and HPV58 were significantly associated with an increased risk of progression, with adjusted odds ratios (aORs) of 6.26 (95% CI: 2.62-14.95), 6.68 (95% CI: 3.30-13.53), and 4.24 (95% CI: 1.51-11.94), respectively. Moreover, women with persistent infections with HPV16, HPV52, and HPV58 had approximately 8-fold, 6-fold, and 5-fold higher risks of progression, respectively, compared with women without infections. Stratified management based on high-risk genotypes-particularly HPV16, HPV52, and HPV58-may help prioritize colposcopy and more intensive follow-up for women at elevated risk, which could contribute to cervical cancer prevention efforts. Trial Registration: Chinese Clinical Trial Registry Center of the World Health Organization International Clinical Trials Registry Platform number: ChiCRT2200055287.

Vulvar and vaginal cancers significantly impact women’s health and quality of life. This study analyzes the prevalence of human papillomavirus (HPV), clinicopathological characteristics, treatment patterns, and survival outcomes, to understand their relationships and better guide prevention and therapy for Chinese patients with vulvar or vaginal cancer. We conducted a retrospective, multicenter study across nine tertiary hospitals located in seven regions of China, including patients diagnosed and treated between 2017 and 2021. Data were collected from medical records and standardized questionnaires, with routine clinical follow-up. Continuous variables were analyzed using the Wilcoxon rank-sum test, while categorical variables were compared using the chi-square test or Fisher’s exact test, as appropriate. Survival outcomes, including overall survival and disease-free survival, were evaluated using the Kaplan-Meier method and multivariable cox proportional hazards regression. A total of 218 patients (131 vulvar, 87 vaginal) were analyzed. HPV infection was significantly higher in vaginal than vulvar cancer (76.1

BACKGROUND:Sleep health is multidimensional, yet existing research has largely examined isolated sleep characteristics, specific population groups, or only one direction of the sleep-depressive symptom relationship. As a result, the bidirectional associations between multidimensional sleep patterns and depressive symptoms remain insufficiently understood. METHODS:The study recruited 75,445 adults between July 2021 and December 2024 through the smart health management digital platform for primary cancer prevention (SmartHMDP-PCP) with 34,344 participants completed the follow-up survey. Sleep was assessed across eight dimensions-sleep midpoint, duration, pre-sleep activities, insomnia, sleep problems, daytime symptoms, medication use, and subjective quality-to construct a composite sleep score (healthy vs. unhealthy). Depressive symptoms were measured using the Self-Rating Depression Scale. Multivariate logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS:Healthy sleep was associated with reduced odds of incident depressive symptoms (OR, 95%CI: 0.62, 0.58-0.67) and increased likelihood of symptom remission (1.55, 1.41-1.69). Maintaining healthy sleep conferred the strongest protection against incident depressive symptoms (0.38, 0.35-0.42) and the greatest likelihood of remission (2.72, 2.42-3.06). In bidirectional analyses, absence of baseline depressive symptoms (0.60, 0.56-0.66), particularly when sustained over time (0.41, 0.37-0.46), was also negatively associated with subsequent deteriorations in sleep patterns, with effect sizes numerically comparable to those observed in the reverse direction. CONCLUSIONS:Multidimensional sleep and depressive symptoms exhibit bidirectional associations of numerically similar magnitude. These findings underscore the importance of integrating sleep health promotion into mental health strategies and highlight the need for interventional and long-term longitudinal research to clarify causal pathways.

e16104 Background: Esophageal cancer is a prevalent malignant tumor of the digestive system, with its development closely related to metabolic reprogramming. Emerging evidence implicates dysregulated cholesterol biosynthesis in ESCC pathogenesis, yet the specific role of geranylgeranyl pyrophosphate (GGPP), a critical intermediate metabolite, remains poorly defined. This study investigates how GGPP drives ESCC progression through protein prenylation-dependent mitochondrial reprogramming and evaluates the therapeutic potential of targeting GGPP synthesis using zoledronic acid (ZA), a clinically approved bisphosphonate for osteoporosis. Methods: The oncogenic role of GGPP was systematically investigated through genetic manipulation of GGPS1 (the rate-limiting enzyme for GGPP synthesis) and pharmacological inhibition with ZA. Transcriptomic profiling and immunohistochemistry were performed on ESCC patient tissues. Functional assays including CCK-8, colony formation, nude mouse xenograft models and seahorse metabolic analysis assessed the impact of GGPP depletion on cell proliferation and mitochondrial oxidative phosphorylation (OXPHOS). GGPP rescue experiments validated metabolite-specific effects. Candidate prenylated proteins were identified through LC-MS and validated by Western blotting. The therapeutic efficacy of ZA was assessed in xenograft-bearing nude mice via tail vein injection, with tumor growth monitored by caliper measurements and endpoint analyses including tumor weight and immunohistochemistry. Results: Transcriptomic analysis revealed significant upregulation of cholesterol biosynthesis genes in ESCC tissues, with GGPS1 expression positively correlating with disease progression. GGPS1 knockdown markedly suppressed ESCC cell proliferation and tumor growth in xenograft models, accompanied by reduced Ki67 expression. Mechanistically, GGPP depletion disrupted protein prenylation, leading to impaired mitochondrial OXPHOS and fatty acid oxidation. Exogenous GGPP supplementation fully rescued the proliferative defects caused by GGPS1 knockdown, confirming GGPP as the critical effector metabolite. Importantly, pharmacological inhibition of GGPP synthesis with ZA significantly inhibited tumor growth in xenograft models, with no apparent toxicity. Conclusions: This study identifies GGPP as a pivotal oncometabolite driving ESCC progression through prenylation-dependent maintenance of mitochondrial OXPHOS. Targeting the GGPP synthesis pathway represents a promising therapeutic strategy for ESCC. The demonstrated preclinical efficacy of zoledronic acid provides strong rationale for clinical repurposing of this FDA-approved drug in ESCC patients, offering a readily translatable therapeutic approach for this aggressive malignancy.

Circulating tumor cells (CTCs) serve as critical biomarkers for diagnosis, treatment monitoring, and prognosis evaluation of lung cancer. However, their trace abundance in blood makes the development of integrated technologies for CTCs isolation, enrichment, and detection with both high specificity and sensitivity a key bottleneck for clinical translation. This study proposed a novel cascade cell-assisted enhanced fluorescence strategy that integrates dual-targeting recognition, cell-mediated cascade assembly, and enzymatic amplification. This dual-targeting strategy achieves efficient capture and enrichment of human non-small cell lung cancer cell line A549 cells through EpCAM antibodies, and uses dual-aptamer probe-mediated EGFR recognition to further improve detection specificity. Subsequently, cascade assembly of acute lymphoblastic leukemia CCRF-CEM cells around target cells combined with enzyme-catalyzed signal amplification constructed a highly sensitive fluorescence-based detection system, with a linear range of 10-104 cells/mL, a limit of detection (LOD) as low as 10 cells/mL, and recovery rates of 94.25%-105.41%. Importantly, clinical validation using whole blood samples from lung adenocarcinoma patients (n = 30) and healthy donors (n = 23) showed significant differentiation (P < 0.05, AUC of 0.728), underscoring its diagnostic potential. Moreover, its modular expandability allows extension to other tumor CTCs detection by replacing target recognition units.

To evaluate the risk of cervical intraepithelial neoplasia, grade 2 or worse (≥ CIN2) in women with normal cervical cytology using extended high-risk human papillomavirus (HR-HPV) genotyping. This study is a population-based, nationwide, multi-center prospective cohort study. A subset of 6853 women with normal cytology and HPV testing results using an extended genotyping assay were included in the analysis. The odds ratio (OR) and adjusted OR (aOR) was calculated using univariate analyses and multivariate logistic regression, with HPV negative and other 9 HR-HPV-positive genotypes (HPV 31, 35, 39, 45, 51, 56, 59, 66, and 68) as reference, respectively. The 3-year cumulative absolute risk was calculated. Over the study period, 87 ≥ CIN 2 cases were identified. Most ≥ CIN 2 cases were positive for HPV 16 (50.6%) or HPV 33/52/58 (46.0%) at baseline. Compared to other 9 h-HPV, HPV 16 (aOR = 20.5, 95% CI: 8.5-49.5), HPV18 (aOR = 10.1, 95% CI: 3.2-31.8), and HPV 33/52/58 (aOR = 4.8, 95% CI: 2.0-11.8) were significantly associated with higher risk of ≥ CIN 2. HPV 16 and 33 had the highest cumulative absolute risk of ≥ CIN2 (25.9% and 22.2%), followed by HPV 18 (15.4%), HPV 58 (11.3%), and HPV 52 (8.1%). Other 9 h-HPV had a lower risk of ≥ CIN 2 (4.7%). Extended HPV genotyping beyond HPV 16/18 (e.g., HPV 33, 52, and 58) might be effective for risk stratification in women with normal cervical cytology. The management of HPV-positive women based on refined genotype-based risk estimations may be a promising strategy for cervical cancer screening. The study was registered at the Chinese Clinical Trial Registry Center of the World Health Organization International Clinical Trials Registry Platform (Registration number ChiCRT2200055287).

To evaluate the clinical performance of Hybribio's 14-type HPV real-time PCR with 16/18 genotyping (HBRT-H14) and its risk stratification utility among women with normal cytology (NILM). From 2017 to 2020, a multicenter cohort enrolled 8,401 women aged 30-64 years with NILM cytology. Baseline HPV testing used HBRT-H14. Women positive for HPV 16/18 were referred for colposcopy; follow-up was annual for 3 years or until the detection of cervical intraepithelial neoplasia grade 2 or worse (CIN2+). Analyses included 6,679 women who completed follow-up. Overall HPV positivity was 11.4%, including 2.3% HPV 16/18. Over 3 years, sensitivity and specificity of HPV positivity for CIN2+ were 92.3% (95% confidence interval [CI]: 84.2-96.4) and 89.6% (88.8-90.3). For HPV 16/18 positivity, sensitivity and specificity were 41.0% (30.8-52.1) and 98.2% (97.8-98.5). Three-year cumulative CIN2+ risk was 20.9% (15.2-28.1) for HPV 16/18-positive women, 6.6% (4.9-8.9) for other types, and 0.1% (0.04-0.2) for HPV-negative women. HBRT-H14 shows strong clinical performance for detecting CIN2+, and HPV 16/18 genotyping provides effective risk stratification among women with NILM cytology. Findings support integration of HBRT-H14 into HPV-based screening pathways with HPV 16/18 genotyping and cytology triage of other types.IMPORTANCEThis multicenter prospective study evaluated the Hybribio 14 high-risk HPV real-time PCR assay (HBRT-H14) in 8,401 women with normal (NILM) cytology under guideline-based follow-up. The assay showed high clinical sensitivity and a very low risk among HPV-negative women, and HPV 16/18 genotyping provided clear risk stratification. These findings deliver large-scale, practice-oriented evidence supporting integration of HBRT-H14 into HPV-based screening pathways that use HPV 16/18 genotyping with cytology triage of other types.

Background:Cervical cancer poses a substantial global health burden, particularly in China where it contributes substantially to incidence and mortality. Conventional HR-HPV screening tests primarily target HPV16/18, limiting efficacy in regions dominated by other oncogenic genotypes and underscoring the need for extended genotyping to refine risk-stratified approaches. Methods:This prospective cohort in Henan Province, China (2017-2020), enrolled 3,299 women aged 21-64 for baseline HR-HPV testing using an extended genotyping assay detecting 14 types and identifying HPV16/18/33/52/58. HR-HPV-positives were followed annually, negatives at year 3. Three-year cumulative CIN2+/CIN3+ risks, sensitivity, specificity, PPV, and NPV were computed independent of cytology. Results:Baseline HR-HPV positivity was 18.3%. Over 3 years, 98 CIN2+ and 60 CIN3+ cases were detected. Absolute CIN2+ risks was highest for HPV16 (32.8%), comparable for HPV18/33/58 (25-28%), with relative risks exceeding 96-fold compared to HR-HPV-negatives. Extended genotyping for HPV16/18/33/52/58 improved CIN2+/CIN3+ sensitivity to 55.1% and 60.0%, respectively (vs. 51.0% and 53.3% for HPV16/18), while maintaining specificities >93%. Conclusions:In Chinese women, non-16/18 high-risk genotypes exhibit risks comparable to HPV16/18, emphasizing the value of extended genotyping in enhancing risk-based screening sensitivity and efficiency in high-burden contexts.

Background:Early screening and detection is essential to reduce morbidity and mortality in esophageal cancer (EC), particularly for individuals at high risk. To reduce the burden and high costs of whole-population screening, we developed a risk score model for individualized risk assessment of esophageal squamous cell carcinoma (ESCC) incidence. Methods:The study was conducted using the Linxian Nutrition Intervention Trial cohort. Cox regression and the points system method were used to build a score-based model for ESCC risk prediction. The receiver operating characteristic (ROC) curve and calibration curve were used to examine the distinction and calibration of the models. Results:A total of 29,408 participants were included in final analysis. During the 10-year follow-up period, 1386 ESCC new cases were identified. Cox regression showed that increasing age, smoking, family history of esophageal cancer, dysphagia, fresh vegetable consumption (≤ 1 time/day), low body mass index (BMI < 18.5kg/m2), not drinking tap water (versus untreated natural water), and tooth loss were independent risk factors of ESCC incidence. The risk score based on 8 risk factors ranged from 0 to 59 points. Compared to subjects with a risk score < 20 points, the ESCC incidence risk increased by 201% for 20 to 39 points and 615% for score of over 39 points. The area under the curve (AUC) value of the risk score estimating ESCC incidence within 3 years was 0.70 (95% CI: 0.67-0.72). Conclusions:Our model effectively stratified the risk of ESCC, demonstrating a potential application in high-risk population identification and ESCC prevention.

Abstract The metabolic impact of cigarette smoke on tumor microenvironment remodeling remains poorly defined. Here, we identify a missense variant in ACER1 that confers elevated risk of esophageal squamous cell carcinoma (ESCC) specifically among smokers, based on a gene-smoking interaction analysis involving 10,716 cases and 12,637 controls. Functional assays demonstrate that the risk allele synergizes with nicotine and benzo[a]pyrene to enhance sphingosine-1-phosphate (S1P) biosynthesis and secretion in ESCC epithelial cells. Integrated single-cell RNA sequencing, spatial proteomics, and multiplex immunofluorescence analyses across multi-stage ESCC samples reveal that this ACER1-driven sphingolipid reprogramming promotes the activation of myofibroblastic cancer-associated fibroblasts (myCAFs). Mechanistically, epithelial-secreted S1P engages the S1PR3-ERK-AKT signaling cascade in fibroblasts, promoting a pro-tumorigenic stromal state. Pharmacological inhibition of S1PR3 markedly suppresses ESCC growth in vivo. These findings uncover a critical gene-environment interaction driving pro-tumorigenic microenvironmental remodeling in esophageal tumorigenesis and highlight a metabolic vulnerability for early detection and therapeutic intervention. Citation Format: Xinying Yue, Jialing Ma, Zifei Yang, Yutong Wu, Qianqian Su, Lina Song, Miaoxin Pan, Dongxu Li, Qingyi Liu, Shasha Liu, Yueping Li, Shaokai Zhang, Siyuan Wang, Li Zhang, Ni Zhang, Wei Ping, Catherine C. Wong, Dongxin Lin, Chen Wu, Jiang Chang. Cigarette smoke-induced sphingosine-1-phosphate drives cancer-associated fibroblasts activation and esophageal cancer carcinogenesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 2274.

Background:The application performance of the Breast Imaging-Reporting and Data System (BI-RADS) in primary healthcare settings remains uncertain. The normativity of BI-RADS classification and the efficacy of breast cancer detection guided by BI-RADS classification were evaluated here. Methods:All data used in the current study were derived from a breast cancer screening cohort baseline database, which consists of 8,996 women aged 35-64 years from Central China. Participants aged 35-44 underwent automated breast ultrasound (ABUS) and handheld ultrasound (HHUS), while those aged 45-64 were screened with ABUS, HHUS, and mammography (MG). All imaging diagnoses were made by radiologists according to the BI-RADS 5th edition classification system published by the ACR in 2013. The distribution of malignant imaging findings and inter-modality agreement on BI-RADS classifications were assessed. Based on pathological results, the area under the receiver operating characteristic (ROC) curve (AUC) was used to assess the performance of breast cancer screening according to BI-RADS-guided referrals. Results:Of individuals found with irregular morphology, 44%, 45.7% and 77.4% were classified as BI-RADS category 4 or higher for HHUS, ABUS and MG, respectively; For those with indistinct margins, the proportion was 81%, 77.5% and 40.8%, correspondingly; For grouped calcifications, they were 100% for HHUS and 85.7% for MG; Meanwhile, 72.7% and 88.9% not parallel (taller than wide) masses were categorized as BI-RADS category 4 for HHUS and ABUS. The concordance of BI-RADS classification was as high as 98.2% between HHUS and ABUS (Kappa = 0.726), whereas it was about 96% between ultrasound and MG (Kappa ranged from 0.21 to 0.25). The BI-RADS guided screening performance for breast cancer showed AUC values of 0.9935 for ABUS, 0.9529 for HHUS, 0.8983 for MG. If the BI-RADS diagnosis of MG was considered in ultrasound-negative women, only the HHUS's performance was boosted, achieving an AUC of 0.9920. Conclusions:Radiologists at primary hospitals can effectively apply BI-RADS based on the malignant features they found. BI-RADS can provide a reliable framework for guiding breast cancer screening in primary healthcare settings.

BACKGROUND:The survival rate of pancreatic cancer is low, and there is a lack of effective treatment. AIM:To explore the epidemiological characteristics of patients with pancreatic cancer in China and compare multiple chemotherapy regimens at different stages. METHODS:This was a retrospective study conducted from 2005 to 2014, involving six cancer hospitals and eight general hospitals across seven geographical regions of China (East, South, North, Central, Southwest, Northwest, and Northeast). Stratified sampling was used based on the population distribution of each region. Efficacy assessments were conducted by Cox proportional hazards regression models. When assessing the effectiveness of various chemotherapy regimens, traditional drugs such as gemcitabine used as monotherapy served as the reference. RESULTS:A total of 3256 patients were included. The median follow-up time was 407 days, and the median overall survival was 183 days. At diagnosis, 56% of patients were already in stage IV. Chemotherapy was administered to 39.73% of patients. In the adjuvant therapy phase, gemcitabine + fluorouracil was superior to gemcitabine monotherapy [hazard ratio (HR) = 0.35, 95% confidence interval (CI): 0.14-0.89]. In fluorouracil-based regimens, other combination regimens did not show effectiveness relative to monotherapy. For first-line treatment in patients with advanced disease, tegafur alone (HR = 0.20, 95%CI: 0.06-0.66), gemcitabine plus cisplatin (HR = 0.16, 95%CI: 0.04-0.70), and tegafur, gemcitabine plus platinum-based agents (HR = 0.32, 95%CI: 0.11-0.91) were associated with a lower risk of death compared to gemcitabine alone. In second-line treatment, there were no significant differences in efficacy among various drugs, but FOLFIRINOX (irinotecan + oxaliplatin + leucovorin + 5-fluorouracil) had an outstanding point estimate (HR = 0.10, 95%CI: 0.01-1.27). CONCLUSION:In China, pancreatic cancer is often diagnosed at advanced stages, emphasizing the need for early diagnosis and treatment. Combined therapies in adjuvant and first-line settings may reduce the risk of death compared with monotherapy, and FOLFIRINOX might offer more significant benefits in second-line treatment.

Cervical cancer remains a significant health burden, and effective screening is essential, yet the age-specific performance of HPV primary screening is rarely studied. This multicenter study evaluates age-specific performance of primary human papillomavirus (HPV) testing as cross-sectional and longitudinal screening for cervical cancer among 28,501 Chinese women. At baseline, HPV screening with cytology triage demonstrates higher sensitivity (96.9

Supplementary Methods, Tables and Figures

BACKGROUND:Lung cancer is the leading cause of cancer-related deaths worldwide, with non-smokers in China accounting for over 40% of cases. Despite the proven efficacy of low-dose computed tomography (LDCT) in early detection and reduction of lung cancer mortality, the current paradigm of lung cancer screening, heavily focused on smoking status and age, may inadequately address the unique risk factors associated with non-smokers, particularly those with a family history of the disease. This study evaluates the cost-effectiveness of LDCT screening for non-smokers with a first-degree relative (FDR) history of lung cancer, a group at particularly high-risk. METHODS:We developed a state-transition Markov model to evaluate the incremental cost-effectiveness ratios (ICERs) of 16 screening strategies for a hypothetical cohort of 100,000 non-smoking individuals aged 50 with a FDR history of lung cancer, considering various starting ages (50, 55, 60, 65 years) and intervals (one-off, annual, biennial, triennial). The willingness-to-pay (WTP) threshold was set at three times China's 2022 per-capita GDP. Sensitivity analyses, scenario analyses and subgroup analysis by sex, were conducted. RESULTS:Compared to no screening, all strategies except one-off screening at age 50, were cost-effective for both sexes. Biennial LDCT starting at age 55 was found to be most effective, with an ICER of CNY 68,932/QALY for males, and CNY 80,056/QALY for females. This cost-effectiveness probability for this strategy was approximately 90% for both sexes. Sensitivity analyses indicated that annual screening at age 55 was optimal without discounting. For males, biennial at age 60 was optimal if the FDR-related odds ratio for lung cancer incidence was below 1.492. Triennial screening at age 55 was optimal for females at full adherence. Ignoring disutility from false-positive results, annual at age 55 was optimal for both sexes. CONCLUSIONS:LDCT screening for non-smokers with a FDR history of lung cancer is cost-effective, especially biennial screening at 55. These findings support the development of more inclusive screening guidelines, which could enhance early detection and reduce mortality rates.