Infectious Agents and Cancer最新文献

Human Papillomavirus (HPV) is a non-enveloped virus with a circular double-stranded DNA genome. It is one of the most common sexually transmitted infections, with high-risk types such as HPV-16 and HPV-18 linked to anogenital and head and neck squamous cell carcinomas (HNSCC). HNSCC includes cancers of the oral cavity, pharynx, larynx, and related regions, caused by carcinogens or persistent viral infections. HPV-positive (HPV+) HNSCC cases are more prevalent in Western countries and exhibit better prognosis and treatment response compared to HPV-negative (HPV-) cases. These differences suggest distinct fundamental differences between each subtype. This study analyzed RNA-seq data from the PanCancer Atlas 2018 dataset to investigate molecular distinctions between HPV + and HPV- HNSCC. Using dimensionality reduction techniques such as Principal Component Analysis (PCA) and Uniform Manifold Approximation and Projection (UMAP), a clear clustering of HPV + cases was observed, suggesting a unique gene expression profile. HPV + tumors exhibited upregulation of genes involved in nucleic acid processing and downregulation of genes associated with apoptosis and epidermis development. These findings underscore the biological differences between HPV + and HPV- HNSCC, offering insights into HPV-driven oncogenesis. Understanding these distinctions may improve patient stratification and inform targeted therapeutic strategies for HNSCC.

Purpose: To explore the failure patterns, outcomes, and treatment response of differentiated non-keratinizing nasopharyngeal carcinoma (DNKC) and to further investigate the role of plasma Epstein-Barr virus (EBV)-DNA in follow-up monitoring, prognostic prediction, and assessment of treatment efficacy in DNKC.

Methods: We retrospectively collected data from patients diagnosed with DNKC from January 2015 to February 2022. The life-table method, Kaplan-Meier survival, and Cox proportional hazards analysis were used for statistical analyses.

Results: A total of 102 patients were included. Of the 77 patients with available EBV-DNA levels, 61 patients (79.2%) had EBV-DNA detectable before treatment. Twenty-seven patients (26.5%) experienced disease recurrence, and 88.9% (24/27) relapsed in the first three years. There were 20 patients who experienced disease recurrence and had pre-treatment EBV-DNA status records. At the time of disease progression, 4 patients initially had undetectable EBV-DNA remained undetectable. Among the 16 patients with initially detectable EBV-DNA, 15 (93.8%) had detectable EBV-DNA. Nodal stage and EBV-DNA levels before treatment were found to be independent prognostic factors for distant metastasis-free survival (DMFS) and disease-free survival (DFS). Those with residual EBV-DNA after induction chemotherapy had significantly inferior DMFS (P = 0.003), DFS (P = 0.006), and overall survival (OS) (P = 0.006) than those without residual EBV-DNA after IC. Those with residual EBV-DNA after radiotherapy had significantly inferior local recurrence-free survival (P = 0.003), DMFS (P < 0.001), DFS (P < 0.001), OS (P < 0.006) than those without residual EBV-DNA after radiotherapy.

Conclusion: Our study highlights the aggressive nature of DNKC, characterized by early recurrence. EBV-DNA levels may serve as a biomarker to monitor treatment response, prognostic prediction, and recurrence surveillance.

Background: Regulatory T cells (Tregs) play a significant role in immune evasion within the tumor microenvironment (TME). Nasopharyngeal carcinoma (NPC) is strongly associated with Epstein-Barr virus (EBV) infection. Previous studies have shown that EBV can suppress immune activity. The relationship between plasma EBV DNA levels and Treg infiltration in NPC remains to be elucidated. Some studies have shown that FOXP3, a Treg marker, is a favorable prognostic factor in NPC. However, relying solely on FOXP3 for Treg identification may be unreliable due to its expression in other cell types. Therefore, this study investigated the impact of tumor-infiltrating Tregs identified by CD4, CD25, and FOXP3 triple markers in NPC and the relationship between these Tregs and EBV infection.

Methods: In this study, 103 NPC patients were included. All tumor slides were stained using multi-immunofluorescence with CD4, CD25, and FOXP3. HALO software was used to analyze whole-slide images. The correlation between two factors was assessed using Spearman analysis. The prognostic value of factors was evaluated using Kaplan-Meier curves and Cox regression.

Results: A significant positive correlation was observed between Treg infiltration in tumor tissues and plasma EBV DNA levels (r = 0.3428, p = 0.02). Higher Treg infiltration was significantly associated with poorer progression-free survival (PFS) (p = 0.03) and was an independent risk factor for NPC progression (p = 0.045). CD25 expression was positively correlated with plasma EBV DNA levels (r = 0.3229, p = 0.03). Furthermore, increased Treg infiltration was negatively correlated with peripheral CD8⁺ T cells (r=-0.3556, p = 0.006). The proportion of peripheral CD8⁺ T cells in patients with advanced-stage NPC was significantly lower compared to those with early stage (p = 0.02).

Conclusion: This study identified tumor-infiltrating CD4⁺CD25⁺FOXP3⁺ Tregs as an independent negative prognostic factor for NPC progression and found higher Treg infiltration positively associated with plasma EBV DNA levels.

Objectives: Cervical cancer is one of the most frequently diagnosed cancers and a leading cause of cancer-related deaths in women in low- and middle-income countries (LMICs), accounting for nearly 85% of the global cervical cancer burden. High-risk human papillomavirus (hrHPV) infection is the main cause of cervical cancer. Easy-to-use, rapid, scalable, high-throughput, and cost-effective HPV tests are urgently needed for low-resource settings. Atila Biosystems' clinically validated ScreenFire HPV Risk Stratification (RS) assay identifies 13 hrHPV in 4 groups based on their oncogenic risk (i.e., HPV16, HPV18/45, HPV31/33/35/52/58, and HPV51/59/39/56/68). While the current standard format is subject to laboratory contamination Atila has developed an innovative, contamination-preventive Zebra BioDome format. Recently we published the analytical performance of ScreenFire RS Zebra BioDome on the BioRad CFX-96 real-time PCR instrument. This current study evaluated its analytical performance on three additional qPCR platforms: Atila Portable iAMP-PS96, Atila Powergene9600 Plus, and Thermo Fisher Quantstudio-7.

Methods: We tested 173 DNA samples from Nigerian women with cervical cancer. These samples were tested simultaneously using the ScreenFire HPV Zebra BioDome assay (M5FHPV-96) on four different real-time PCR machines (Atila portable iAMP-PS96, Atila Powergene9600 Plus, Thermo Fisher QuantStudio-7, and BioRad CFX-96). We used overall agreement rate and unweighted kappa values to compare different platforms.

Results: The overall agreement for detection of hrHPV using Atila portable iAMP-PS96 was 96.5% with kappa value 0.95 (95% confidence interval: 0.91-0.99) compared to Thermo Fisher QuantStudio-7, and 97.1% with kappa value 0.96 (95% confidence interval: 0.92-0.99) compared to BioRad CFX-96. For genotype HPV16 and risk stratification (RS) genotype groups (HPV18/45, HPV31/33/35/52/58, and HPV51/59/39/56/68) agreement rates were all > 98.3%. For Atila Powergene9600 Plus the overall agreement was 98.8% with a kappa value of 0.98 (95% confidence interval: 0.96-1.0) compared to Thermo Fisher QuantStudio-7, and 96.5% with a kappa value of 0.96 (95% confidence interval: 0.94-0.99) compared to BioRad CFX-96. The agreements for the HPV16 and RS genotype groups (HPV18/45, HPV31/33/35/52/58, and HPV39/51/56/59/68) were at least 98.3%.

Conclusion: The novel ScreenFire HPV Zebra BioDome format produced highly concordant hrHPV positivity and RS genotype results on all four qPCR platforms. The data suggests that this innovative technology has the potential to improve HPV testing uptake in low-resource settings without further investment in purchasing new equipment.

Background: The relationship between immune cells and colorectal cancer (CRC) development has been extensively studied; however, the mediating role of gut microbiota in this relationship remains poorly understood.

Methods: We utilized summary data from genome-wide association studies (GWAS) to analyze 731 immune cell phenotypes, 473 gut microbiota, and CRC-related data. A two-step mediation analysis was employed to identify mediating gut microbiota. The primary analysis method was inverse variance weighting (IVW), supplemented by MR-Egger, simple mode, weighted median, and weighted mode analyses. Robustness of the results was ensured through systematic sensitivity analyses.

Results: Our analysis identified 13 immune cell phenotypes significantly associated with CRC, including 10 protective factors and 3 risk factors. Additionally, 13 gut microbiota showed significant associations with CRC, comprising 8 protective factors and 5 risk factors. Mediation analysis revealed that 4-gut microbiota (1 order, 1 family, 1 genus, and 1 unclassified) mediated the relationship between immune cells and CRC. For instance, unclassified CAG - 977 mediated the effects of FSC-A on NK and NKT %lymphocyte on CRC risk, with mediation proportions of 11% and 12.3%, respectively. Notably, 22.3% of the protective effect of EM CD8br %CD8br on CRC was mediated through order Francisellales.

Conclusion: This study provides evidence for a potential causal relationship between immune cells, gut microbiota, and CRC, highlighting the mediating role of specific gut microbiota. These findings offer new insights into the pathogenesis of CRC and may inform future therapeutic strategies.

Background: HPV testing has become the recommended primary screening method for cervical cancer in China. However, referring all HPV-positive patients for colposcopy is not practical. This study monetized clinical performance metrics to evaluate the relative performance of 10 secondary triage strategies compared to referring all patients for colposcopy.

Methods: Using real-world HR-HPV sample data and strictly adhering to the HPV-FRAMEWORK, a Markov model was employed to simulate the missed diagnosis losses and health utility losses associated with referring all patients for colposcopy. These losses were monetized using one-time 2023 per capita GDP in China. Incremental net benefits of secondary triage strategies were calculated to identify the optimal strategy. Extensive sensitivity analyses were conducted to assess parameter and sample uncertainty. Additionally, the technical suitability of strategies was explored in the context of healthcare resource allocation in China.

Results: Solely relying on HPV genotyping for secondary triage is not recommended, and necessary secondary triage testing should be implemented. p16 performed better than LBC, particularly in the overall sample and in most age groups. The strategy of HPV16/18+ or (OH-HPV+ and p16+) was the most attractive, with an incremental net benefit of US$492,473.78 compared to referring all patients for colposcopy. Extensive sensitivity analyses confirmed the robustness of these results. Considering healthcare resource allocation in China, p16 demonstrated higher technical suitability.

Conclusion: Based on real-world sample data and the monetization of clinical performance metrics, this study recommends p16 as the secondary triage technology. The HPV16/18+ or (OH-HPV+ and p16+) strategy is not only the most attractive but also holds high potential for large-scale implementation in China.

Introduction: The COVID-19 pandemic introduced challenges including delaying elective surgery. For cancer patients, reducing delays is preferred to prevent unfavorable outcomes. there is a lack of consensus regarding the optimal timing of elective surgery following a SARS-CoV-2. This study aimed to find the optimal time to elective surgery to minimize 30-day postoperative morbidity and mortality.

Methods: This is a retrospective chart review of all adult patients who underwent elective surgery with a confirmed preoperative COVID-19 diagnosis between September 2020 and April 2023. Patients' elective surgeries delays were examined to determine the optimal time to surgery in terms of postoperative complications. Analysis was controlled for age, ASA score, comorbidities, and smoking status.

Results: 358 records examined, 94.7% had delayed surgery and 5.3% had cancelled surgery. The optimal time to surgery was ≥ 17 days to minimize postoperative pulmonary complications [OR: 0.299, p = 0.048], other postoperative complications [OR: 0.459, p = 0.01], and a decrease in length of hospital stay. In multivariate analysis, the only significant predictors for postoperative complications were time to surgery; surgery ≥ 17 days after diagnosis had better postoperative outcomes [p < 0.001], and COVID-19 symptoms status [p = 0.019].

Conclusion: The best time to surgery in this cohort is at least 17 days (or a range of 2-3 weeks) for optimal results. Further research is needed to investigate the effect of such delays on oncological outcomes in this cohort.

Background: Limited data are available about the distribution of human papillomavirus (HPV) among women undergoing cervical cancer screening in Mozambique. We describe the prevalence of high-risk HPV risk groups detected in women who participated in the MULHER Study, a prospective trial of Mozambican women undergoing cervical cancer screening with HPV testing.

Methods: From January 2020 to January 2023, 9,014 women aged 30-49 years in Maputo City and Gaza Province, Mozambique underwent cervical cancer screening. Cervicovaginal samples were self-collected (97.5%) or provider-collected (2.5%) and primary HPV testing was performed using the GeneXpert HPV testing platform (Cepheid Inc, USA) which provided data on HR-HPV risk groups: HPV16, HPV18/45 and 11 other HR-HPV types in aggregate. Women with a positive HR-HPV test underwent visual assessment using dilute acetic acid applied to the cervix for treatment decisions.

Results: Of the 9,014 women enrolled in the MULHER Study, 8,954 (99.3%) had a valid HPV test result. Of those, 2,805 (31.3%) tested positive for at least one HR-HPV group: HPV16 (n = 475, 16.9%), HPV18/45 (n = 686, 24.6%) and other HR-HPV (n = 2,150, 77.1%). A total of 17.8% were positive for multiple HPV HR groups. HR-HPV infection prevalence was higher among women living with HIV (WLWH) than HIV-negative women (39.7% vs. 24.3% respectively; p < 0.001). WLWH were more likely to test positive for HPV18/45 (p = 0.03) and for two or more HR-HPV risk groups (P < 0.0001) compared with HIV-negative women. HPV16 was the most frequently detected HR-HPV group (56.7%) among women diagnosed with invasive cervical cancer.

Conclusions: HR-HPV prevalence was high among Mozambican women aged 30-49 years, especially among WLWH, consistent with the high burden of cervical cancer in this population. HPV16 was the most common HR-HPV group among women with cervical cancer. Further study is needed to determine the role of HR-HPV genotyping in follow-up and treatment in Mozambique.

Objective: To assess the triage value of multigene methylation testing for cervical intraepithelial neoplasia 2 and above (CIN2+) in high-risk human papillomavirus (hrHPV) positive patients.

Methods: 634 hrHPV-positive cases were selected from the gynecology outpatient clinic at Hainan Women and Children's Medical Center between July 2022 and April 2024. Out of these, 274 patients were excluded based on the inclusion and exclusion criteria. A total of 360 patients were evaluated for hrHPV, cytology, histopathology, and DNA methylation across multiple loci. These patients were categorized into five groups based on their histopathological diagnoses: control group, CIN1 group, CIN2 group, CIN3 group, and cervical cancer (CC) group. The triage value of multigene methylation testing for CIN2 + in hrHPV-positive patients was evaluated by calculating the positivity of candidate gene methylation, sensitivity, specificity, area under the curve (AUC), and other performance indicators.

Results: Among the 17 candidate genes (ST6GALNAC5, PAX1, AJAP1, CDKN2A, ZNF671, GATA4, MAL, POU4F3, RXFP3, JAM3, MIR124, LHX8, SOX1, ASTN1, SOX17, DLX1, and ITGA4), ITGA4 methylation testing demonstrated the highest diagnostic efficacy for detecting CIN2 + lesions, with an AUC of 0.866 (95% confidence interval [CI]: 0.806-0.925). This method exhibited a sensitivity of 75.32% (95% CI: 0.647-0.836) and a specificity of 96.45% (95% CI: 0.936-0.981). The combined methylation test, which included all candidate genes, showed a higher specificity of 97.87% (95% CI: 0.954-0.990) compared to any individual gene methylation test. However, its sensitivity was lower, at 72.73% (95% CI: 0.619-0.814). Furthermore, the diagnostic accuracy of combining HPV16/18 testing with all candidate gene methylation tests for the diagnosis of CIN2 + was significantly greater than when HPV16/18 testing was combined with cytology. This combined approach had an AUC of 0.907 (95% CI: 0.858-0.955), a sensitivity of 72.73% (95% CI: 0.619-0.814), and a specificity of 98.58% (95% CI: 0.964-0.995).

Conclusion: Multigene methylation testing is an efficient triage test for CIN2 + in hrHPV-positive patients and has potential value in clinical practice. Combined HPV16/18 and multigene methylation testing for the triage of CIN2 + is significantly better than combined HPV16/18 and cytology testing.