Wiley最新文献

Current epidemiological thinking is that classic Hodgkin lymphoma (cHL) comprises multiple aetiologically distinct disease entities that may in part be defined by either histological subtype or the presence of Epstein-Barr virus (EBV) in the malignant cells, or by both. This study aimed to advance our understanding of epidemiological differences between cHL subtypes, in particular EBV-positive and EBV-negative cHL. We retrospectively collected and EBV-typed 1992 cHL primary tumour tissues from among all 2811 patients diagnosed with incident HL in Denmark in the period 1990 through 2010 'Hodgkin lymphoma in Denmark' [HOLYDAN] project. Based on characteristics of retrieved samples combined with additional information from national registers, we projected nationwide age-, sex-, histology- and EBV-specific cHL incidence rates. The analyses demonstrated age- and sex-dependent variation in histology- and EBV-tumour status-specific cHL incidence rates, details of which yielded new aetiological clues. cHL incidence increased markedly around the age of puberty, irrespective of histological subtype and EBV status. The incidence of all subtypes of cHL increased with age after age 50 years, with the exception of EBV-negative nodular sclerosis cHL in females, which therefore showed a single peak in incidence and was higher than in males among young adults. These results were obtained in a small homogeneous population and might, therefore, only apply to rich, industrialised, Western populations. Nevertheless, we propose that puberty creates an immunological host environment conducive to cHL development irrespective of EBV status and histology, and that age-related decline in immune function facilitates the development of both EBV-positive and EBV-negative cHL.

As a tumor suppressor gene, CCDC6 encodes a coiled-coil domain-containing protein that is ubiquitously expressed and involved in crucial cellular processes such as DNA damage response and apoptosis, although its precise mechanisms remain elusive. Initially identified as part of a fusion gene, CCDC6 can form fusion genes with a variety of proto-oncogenes, including both kinase- and non-kinase-coding genes, thereby facilitating oncogenesis. Alterations in CCDC6 expression across various cancers underscore its intricate role and potential influence on the efficacy of anticancer therapies. Recent findings have demonstrated that CCDC6 can undergo liquid-liquid phase separation (LLPS) and facilitate the LLPS of its associated fusion proteins, providing new perspectives on its functional characterization and potential therapeutic implications in related diseases. We present a comprehensive overview of CCDC6, encompassing its protein characteristics and physiological and genomic aspects. Furthermore, we explored the association between CCDC6 alterations and carcinogenesis, as well as their implications for therapeutic interventions. The objective of this review is to furnish the medicinal community with current information and valuable insights pertaining to diseases associated with CCDC6.

Chemotherapy is an essential component of cancer treatment, as outlined in the National Comprehensive Cancer Network (NCCN) guidelines for Sub-Saharan Africa (SSA). Lack of access to treatment is a key driver of impaired survival rates. This study assessed patient-perceived barriers to chemotherapy in SSA according to the five dimensions of access to care: availability, accessibility, accommodation, affordability, and acceptability. Telephone interviews were conducted with 553 randomly selected cancer patients (or caretakers), registered between 2018 and 2019 in 11 urban population-based cancer registries across nine countries in SSA. Malignancy types included breast, cervical, prostate, and colorectal cancer; non-Hodgkin lymphoma; and Kaposi sarcoma. Patients rated barriers using a 3-point Likert scale. Barriers to chemotherapy and their associations with patient characteristics were analysed using multivariate ordinal regression analysis. Major barriers included accessibility (cost of transport), affordability (cost of treatment, being absent from home), and acceptability (lack of knowledge/awareness and fear of treatment). Results varied between countries: affordability was especially severe in the Republic of Congo, while in Gabon, fear of treatment prevailed. Knowledge and awareness were particularly concerning in Ethiopia and Zimbabwe. A combined educational level and self-reported wealth variable, and national human development index (HDI) were consistently associated with reported barriers. Overall, 58.6% of participants received chemotherapy, while 13.2% were recommended chemotherapy but did not receive it. A higher HDI correlated with an increased probability of receiving treatment. A complex set of barriers influenced patients' non-receipt of treatment. Regionally adapted strategies, including psychosocial support, financial assistance for vulnerable groups, and education, are essential to improve treatment uptake in SSA.

This study examined the associations of diabetes status, duration, and age at onset with lung cancer risk in the China Kadoorie Biobank. We prospectively assessed the association between diabetes status and lung cancer risk in 510,148 cancer-free participants, with analyses of duration and age at onset among 29,962 participants with diabetes at baseline. Multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression models, and effect modification was assessed across stratified subgroups using likelihood ratio tests. During a median 9.17-year follow-up, 5007 lung cancer cases occurred. Compared with participants without diabetes, those with diabetes had a higher lung cancer risk (HR = 1.15, 95% CI: 1.01-1.32). Diabetic patients with onset <40 years showed a 2.81-fold higher lung cancer risk (95% CI: 1.31-6.02) compared to ≥60-year onset groups. Longer duration (≥15 vs. <1 year) was associated with increased risk (HR = 2.06, 95% CI: 1.33-3.19). The association with diabetes status was stronger among individuals with below-median physical activity, while the association with diabetes duration was more pronounced in overweight participants. Overall, these findings indicate that diabetes, especially with earlier onset and longer duration, significantly increases lung cancer risk, highlighting the need for screening and targeted management in high-risk populations.

Persistent infection with human papillomavirus (HPV) is associated with an increased risk of head and neck cancers (HNC), particularly oropharyngeal cancer. This longitudinal cohort study investigated the prevalence and dynamics of oral HPV infection among healthy adults in South India. A total of 5325 participants were enrolled, and demographic, behavioral, and oral gargle samples were collected. HPV deoxyribonucleic acid (DNA) was detected using nested PCR (PGMY/GP) and genotyped by Sanger sequencing. HPV16 messenger ribonucleic acid (mRNA) expression was analyzed by reverse transcriptase polymerase chain reaction (RT-PCR) and validated using droplet digital polymerase chain reaction (ddPCR). Logistic regression analyses were performed to estimate odds ratios. At baseline, 5011 samples were analyzed; 274 (5.5%) were HPV-positive and 4737 were negative. Among 3792 initially HPV-negative participants followed up, 126 (3.3%) acquired new infections (median 8 months; range, 6-15 months). Of 274 baseline HPV-positive individuals, 241 were followed up: 24 (10%) showed persistence, while 217 (90%) cleared infection after a median of 9 months (range, 6-20 months). Sanger sequencing of 471 samples from prevalent and incident infections yielded 290 (61.6%) high-quality sequences; 284 (98%) were HPV16, with isolated detections of HPV18, HPV66, HPV70, and HPV89. Ten novel variants were identified-nine HPV16 and one HPV89-while remaining sequences aligned with established Indian cervical HPV lineages. None of the 176 HPV16 DNA-positive samples analyzed expressed mRNA by RT-PCR, confirmed in 136 samples using ddPCR. Oral HPV infection among healthy individuals in India appears predominantly transient. Long-term monitoring may elucidate the oncogenic potential of oral HPV in this population.

The objective of this systematic review was to identify the evidence of testicular cancer risk for people with intersex conditions. This assessment is hoped to help refine risk stratification tools for assessing gonadal malignancy risk and guide the development of more robust evidence-based management strategies. The literature was searched in Ovid MEDLINE, Embase, and Cumulative Index of Nursing and Allied Health using a search string developed by a multidisciplinary team. The protocol was registered at Prospective Register of Systematic Reviews as CRD42021231313. A total of 3608 articles were found. After selection, 301 publications were included (1215 individuals). The results identified significant evidence that pre-pubertal gonadectomy may be linked to lower rates of malignant gonadal changes for patients with partial gonadal dysgenesis, Turner's syndrome with Y-chromosome material, complete androgen insensitivity, partial androgen insensitivity, and patients with ovotestis/es. The evidence was not significant for patients with complete gonadal dysgenesis, Klinefelter syndrome, nor WT1-related syndromes. Specific cancer outcomes were unable to be assessed due to small sample sizes and thus it is unknown if clinically significant cancer outcomes are meaningfully altered by pre-pubertal gonadectomy. Importantly, the quality of data on the topic of gonadal malignancy in intersex patients with testicular tissue was determined to be poor overall. The quality was relatively more robust regarding the conditions of Complete Androgen Insensitivity, Klinefelter syndrome, and patients with ovotestis/es. More high-quality research is needed to draw specific conclusions on the risks and benefits of performing pre-pubertal gonadectomy for intersex patients. When counseling these patients, clinicians should be transparent regarding the paucity of data supporting pre-pubertal gonadectomy.

Conditional survival provides insights into the evolution of prognosis over time and reveals changing associations of prognostic factors during disease progression. Data on the temporal evolution of prognostic factors in glioblastoma remain scarce. We analyzed 315 patients with IDH-wildtype glioblastoma from a prospectively collected registry (01/2008-06/2017). Our primary outcome was 12-month conditional survival (CS), defined as the probability of surviving the next 12 months given survival for "s" months. This analysis was conducted at five landmarks (s = 0, 6, 12, 18, 24) for baseline prognostic factors, including tumor volume compartments. 12-month conditional survival estimates at s = 0, 6, 12, 18, and 24 months from diagnosis were 0.51 (95% CI 0.45-0.56), 0.46 (95% CI 0.39-0.52), 0.41 (95% CI 0.33-0.49), 0.43 (95% CI 0.33-0.52), and 0.56 (95% CI 0.42-0.67), respectively. At diagnosis (s = 0), 12-month survival estimates varied significantly with age >60 at diagnosis, preoperative tumor rim volume >20 cm³, absence of O⁶-methylguanine-DNA methyltransferase (MGMT) promoter methylation, postoperative KPS ≥70, residual postoperative tumor >1 cm³, or biopsy only. Residual tumor volume mainly influences survival in the initial months following surgery, while MGMT promoter methylation and age remain significant predictors beyond this period. These findings may refine stratification strategies in recurrent glioblastoma trials.

As cervical cancer screening shifts from cytology to HPV testing, clarifying the type- and age-specific natural history of HR-HPV is crucial, especially in regions with bimodal prevalence patterns where longitudinal data remain limited. We analyzed baseline HR-HPV-positive participants from the control arm of a bivalent HPV-16/18 vaccine trial in China, with follow-up over 5.5 years. Cox regression and competing risk models were applied to evaluate the progression, clearance, and persistence of these HR-HPV infections. Among 534 HR-HPV-positive women at baseline, 98 CIN2+ lesions were identified (52 at baseline, 46 during follow-up). HPV-16 and HPV-31 exhibited the highest immediate CIN2+ risk (21.1%), followed by HPV-33 (17.1%) and HPV-58 (12.7%). When stratified by baseline cytology, the LSIL+ group showed the highest immediate risk of CIN2+ (29.5% among the HR-HPV-positive participants), followed by the ASC-US (10.5%). In the longitudinal analysis, competing risk models revealed significant type-specific differences in progression (Gray's test P = 0.0158) and clearance (Gray's test P <0.0001). HPV-16, -31, -18, and -58 showed relatively high progression (27.1%, 19.2%, 16.1%, and 11.2%) and low clearance (72.9%, 69.2%, 83.9%, and 88.8%). CIN2+ risk was strongly genotype-dependent; beyond HPV-16/18, types -31, -33, and -58 also warrant particular attention in screening and clinical management. Additionally, although a slightly higher CIN2+ progression risk was observed in younger women compared to older women, the difference was not statistically significant (Gray's test P = 0.4389), indicating the need for confirmation in larger studies. These findings enhance the understanding of the natural history of type-specific HR-HPV and age-specific progression in initially screen-positive populations.

Self-sampling for human papillomavirus (HPV) is an established strategy to increase participation in cervical screening. We previously reported a randomized trial targeting women who had not attended screening after >10 invitations, where sending of self-sampling kits resulted in a 19% attendance and a positive predictive value (PPV) for high grade lesions (HSIL+) of 40%, despite no triaging after the HPV test. Because of the striking results, the intervention was extended to all women resident in Stockholm County, Sweden, in the years 2019/20, who had not attended screening >10 years (N = 42,409). Participation was 35.6% and 11.6% of the participating women were HPV-positive. Among these, there were 43 cases of invasive cervical cancer and 319 cases of high-grade lesions. The PPV was particularly high for HPV16/18 positive women (12% for invasive cancer and 59% for HSIL). In summary, participation with HPV self-sampling among long-term non-attenders in the real-life program was considerably higher than in the research setting and the high yield of HSIL+ implied high effectiveness.