International Journal of Cancer最新文献

Hodgkin lymphoma (HL) is associated with Epstein-Barr virus (EBV) infection in a subset of cases. We previously showed that the incidence of HL in Taiwan increased ~2.5-fold between 2001 and 2020, particularly among young women with the nodular sclerosis (NS) subtype. In this nationwide multicenter study, we evaluated EBV status in HL to determine its impact on clinicopathologic features and survival outcomes. We found that the proportion of EBV-associated HL in Taiwan declined over the past two decades, from 39% to 27%. EBV-positive frequency exhibited a bimodal age distribution, peaking in children < 10 years (63%) and adults > 70 years (80%), with the lowest frequency in patients 20-29 years (11%). Compared with EBV-negative patients, EBV-positive patients were older (53.5 vs. 32.9 years; p < 0.001), predominantly male (73.1% vs. 48.7%; p < 0.001), more likely to have nodal disease (83.3% vs. 74.2%; p = 0.003) and mixed cellularity histology (37.1% vs. 11.4%; p < 0.001), and had inferior 10-year survival (56.3% vs. 85.7%; p < 0.001). Adverse prognostic factors in HL included older age (> 60 years), B symptoms, non-NS histology, EBV-positivity, advanced-stage disease (Stage III-IV), and a high International Prognostic Score (IPS, 4-7). On multivariate analysis, older age and a high IPS retained prognostic significance. Large registry datasets from Taiwan and the US further demonstrated that survival outcomes have improved over the past two decades. Female patients and those with the NS and nodular lymphocyte-predominant subtypes had significantly better survival. These findings provide insight into the biological impact of EBV in HL and help inform strategies for disease prevention and management.

BRCAness, a phenotype associated with homologous recombination deficiency, has not been fully characterized in triple-negative breast cancer (TNBC) with residual disease after neoadjuvant chemotherapy (NAC), especially regarding prognosis and regimen-specific postoperative management. We analyzed 137 patients with TNBC who had residual invasive disease after NAC. BRCAness status was assessed in surgical specimens using multiplex ligation-dependent probe amplification (MLPA). Its associations with clinicopathological features and survival were evaluated according to NAC regimen, and prognostic models for disease-free survival (DFS) and overall survival (OS) were developed by combining BRCAness with clinicopathological variables. BRCAness was identified in 42.3% of tumors and was associated with high histological grade, high Ki-67, and perineural invasion. Patients with BRCAness-positive tumors had worse survival than those with BRCAness-negative tumors (5-year DFS, 50.0% vs. 68.2%, p = 0.020; 5-year OS, 58.6% vs. 78.1%, p = 0.014). This prognostic effect was evident in patients treated with anthracycline-based NAC, but not in those treated with platinum-based regimens. Models incorporating BRCAness showed good discrimination (DFS C-index, 0.70; 95% CI, 0.62-0.78; OS C-index, 0.75; 95% CI, 0.69-0.81). Among BRCAness-positive patients who had received anthracycline-based NAC, adjuvant chemotherapy was associated with better survival (5-year DFS, 55.6% vs. 27.3%, p = 0.035; 5-year OS, 66.7% vs. 36.4%, p = 0.023). BRCAness was associated with poorer outcome in residual TNBC after NAC and may help identify patients with different prognoses and postoperative treatment patterns.

Evaluation of arterial resection (AR) during pancreatoduodenectomy (PD) remains limited. This study compares PD with AR to PD with venous resection (VR) and no vascular resection (NVR). Patient demographics, outcomes, and changes over 5 years are evaluated. In this study, NSQIP data was analyzed comparing patients undergoing PD with AR to NVR and VR. Demographics and 30-day post-operative outcomes were compared, and multivariable modeling evaluated factors associated with serious complications and mortality. Propensity score matched (PSM) analysis compared AR to NVR, AR to VR, and VR to NVR. We evaluated 28,083 patients with 4.1% having AR and 10.9% having VR. After demographic adjustment, both AR (1.40; p < 0.001) and VR (OR 1.32; p < 0.001) were independently associated with serious complications and mortality (AR: OR 2.03; p = 0.002; VR: OR 1.43; p = 0.043). PSM supported increased serious complications (+4.9% VR, p < 0.001; +5.40% AR, p = 0.008) but not mortality (+0.4% VR, p = 0.323; +1.4% AR, p = 0.067) compared to NVR. AR did not increase the risk of complications or mortality compared to VR following PSM. Evaluating AR/VR from 2017 to 2021 shows consistent demographics but increasing neoadjuvant treatment (40.2%-48.9%; p < 0.001). Length of stay has decreased (12.3-9.6 days; p < 0.001), while serious complications (19.7%-22.1%) and mortality (1.7%-3.1%) remained similar. Results demonstrate that arterial (and venous) resection during PD is independently associated with 30-day serious complications compared to without vascular resection. However, absolute morbidity rates during vascular resection may be acceptable in selected patients and appear to be similar with arterial and venous resection. Future studies evaluating long-term outcomes are needed.

Type I to III cervical transformation zones (TZ-1 to TZ-3) may have various effects on cervical cancer screening and diagnostic outcomes. This study aims to evaluate the clinical utility of the cytological PAX1/JAM3 methylation (CISCER) assay in cervical cancer screening, especially in TZ-3 women. Between November 2020 and October 2022, 1782 women referred for colposcopy underwent liquid-based cytology (LBC), high-risk human papillomavirus (hrHPV) genotyping, and CISCER testing. After applying inclusion criteria, 1398 women were analyzed, including 1190 with documented TZ classification. Diagnostic performance for detecting cervical intraepithelial neoplasia grade 3 or worse (CIN3+) was compared across TZ subgroups. For CIN3+ detection, CISCER showed sensitivities of 67.4%, 72.0%, 48.3%, and 81.5% and specificities of 91.0%, 94.2%, 91.3%, and 89.8% in all women, TZ-1, TZ-2, and TZ-3, respectively. Compared with LBC ≥ ASC-US, hrHPV positivity, or HPV16/18 positivity, CISCER achieved the highest diagnostic accuracy, with AUC values of 0.792, 0.831, 0.698, and 0.856 across the respective groups. In both the overall cohort and TZ-3 subgroup, CISCER positivity was associated with the highest CIN3+ risk (34.6% and 31.4%) and required the fewest colposcopy referrals per CIN3+ detected (2.9 and 3.2). Combining hrHPV testing with CISCER further improved risk stratification. CISCER demonstrated superior diagnostic performance across TZ types, particularly in TZ-3, enabling improved CIN3+ risk discrimination while substantially reducing unnecessary colposcopy referrals compared with conventional cytology and HPV genotyping.

Globally, Japan has the largest proportion of individuals aged ≥ 85 years. However, epidemiological studies on cancer in this age group are limited. This study aimed to investigate cancer trends and characteristics among the oldest-old adults (aged ≥ 85 years) in Japan, using population-based national and prefectural cancer registry data on incidence, mortality, trends, stage, and treatment patterns, and compared them with those of young-old adults (aged 65-84 years). From 1995 to 2020, the number of cancer cases among the oldest-old increased more than four-fold, with a significant average annual percent change of +5.9% (confidence interval: 5.4-6.3), surpassing growth in both the overall and young-old populations, and accounting for 15.7% of all cases in 2020. The oldest-old showed higher proportions of skin and gallbladder/bile duct cancers, and rising proportions of breast and prostate cancers. The group was more likely to be diagnosed at unstaged or advanced stages of cancer. Aggressive treatment was less commonly administered to this group, even when the stage at diagnosis was similar to that in the younger-old patients. These findings highlight distinct epidemiological and clinical cancer trends in the oldest-old. Since cancer incidence among the oldest-old will likely continue to rise, targeted healthcare and policy interventions that consider the impact of this age group at both individual and societal levels are urgently needed. To address the needs of an aging population, reconsideration of prevention, detection, and management, including guidelines and specialist availability, is suggested. Moreover, Japan must consider further cancer research in this rapidly increasing population.

We conducted a controlled trial among 5626 early adolescent women vaccinated in 2007-2009 against human papillomavirus (HPV) types 16/18 to evaluate the impact of high-intensity versus low-intensity cervical screening, respectively at ages 22/25/28 and 28 years with squamous-cell intraepithelial lesions (SILs) as the end-point. Over the 16-year follow-up, most of the cytologically and/or histologically confirmed low-grade and high-grade SILs were associated with non-vaccine-targeted, medium oncogenicity HPV types 33/35/52/58 belonging to clade A9. The low-intensity cervical screening was non-inferior to the high-intensity screening in the identification of these lesions. Possibly, the transition from cervical infections with vaccine-covered HPV types to infections with non-vaccine-covered HPV types contributes to more manageable occurrence of the screen-detected cervical lesions. Reduction of cervical screening among vaccinated women to a minimum may be warranted to balance the harm-benefit ratio of screening.

Lynch syndrome, a prevalent hereditary cancer predisposition, is frequently caused by pathogenic variants in the MutL homolog 1 (MLH1) mismatch repair gene. However, a significant proportion of MLH1 missense variants remain classified as variants of uncertain significance (VUS), creating clinical ambiguity. Functional validation assays in vertebrate models are crucial to assess the pathogenicity of these VUS. We previously reported the rare MLH1 NM_000249.4:c.335A>G (p.His112Arg) variant in individuals with cancer histories within the Qatar Genome Program. To assess its functional impact, we established the MLH1 p.His112Arg variant in the human colorectal cancer cell line, COLO205, using CRISPR-Cas9 technology. Isogenic wild-type (WT) and variant-carrying cells were xenotransplanted into the zebrafish. Tumor growth was quantified via fluorescence microscopy at 24 and 72 h post-injection. Zebrafish xenografted with MLH1 p.His112Arg cells exhibited a significant increase in tumor area compared to WT. This accelerated growth was associated with a significant upregulation of the proliferation marker MKI67 in variant-carrying tumors, while cyclin D1 (CCND1) and proliferating cell nuclear antigen (PCNA) (key regulators of cell cycle progression and DNA replication, respectively) expression remained unchanged, despite a tendency for increased expression. Furthermore, our functional characterization of the MLH1 p.His112Arg variant in COLO205 cells showed an enhanced proliferation capacity compared to the WT cell line, as well as increased cell viability and decreased apoptotic susceptibility when subjected to methylation-induced DNA damage. The MLH1 p.His112Arg variant confers a tumor-promoting phenotype in an in vivo zebrafish model, providing functional evidence that supports its reclassification from VUS to likely pathogenic.