Infectious Agents and Cancer最新文献

Background/objectives: Epstein-Barr Virus (EBV) is a ubiquitous virus associated with a variety of diseases including cancers. Evidence has emerged that the C promoter is methylated in many EBV-associated malignancies, whereas in free virion DNA it is unmethylated. We have developed and evaluated a methylation-specific PCR assay for the EBV C Promoter (MSPCP) that can be applied to human biological specimens to quantify EBV methylation.

Methods: Two sets of methylation-specific primers were designed to anneal to bisulfite-converted DNA sequences with 3 CpGs in the forward primer binding site, and 2 CpGs in the reverse primer binding site. We evaluated this method in synthetic oligonucleotides, DNA extracted from cell lines, virion supernatants, and a variety of clinical specimens. EBV methylation of Cp, as measured by MSPCP, was validated with two orthogonal methods in select samples.

Results: In contrived samples, this method had a linear range between 0-100% methylation. Application of this assay to DNA extracted from 11 formalin-fixed paraffin-embedded biopsy specimens showed high-level C promoter methylation in EBV-associated tumors (94-100%) but not in EBV-associated lymphoid hyperplasia. High-level EBV methylation was also detected in cell-free DNA extracted from the plasma of 13 patients with EBV-associated Hodgkin lymphoma. In contrast, EBV methylation was either not-detected, or detected at very low levels, in saliva from 25 adults in a general university population consistent with the presence of virion DNA.

Conclusions: MSPCP is a simple, rapid and accurate method that characterizes the methylation status of the EBV C promoter, which may be useful in a variety of research and clinical settings.

Since its emergence, the coronavirus (SARS-CoV-2) outbreak has been a pandemic responsible for about 7 million deaths worldwide. Numerous studies have been conducted to determine the virus's multiorgan system involvement, particularly its relation to cancer biology. Spontaneous regression of cancer has been observed in some patients with the coronavirus, which may be attributed to the virus's ability to trigger specific immune responses that can be oncolytic and help reduce and eliminate oncogenic cells. This study aims to explore the paradoxical effects of COVID-19 in inducing cancer regression. The paradoxical effect of SARS-CoV-2 infection has been attributed to the possibility of a heightened immune activation possibly triggered by the virus, and some of these include increased levels of cytokines such as interferon and tumor necrosis factor-alpha (TNF-α), as well as the activation of T cells and natural killer (NK) cells. COVID-19-induced cancer regression presents new perspectives on the relationship between viral infections and the immune system's antitumor capabilities. This would help foster future research investigating specific immune pathways activated during SARS-CoV-2 and discover how these can be therapeutically harnessed to aid cancer regression.

Background: High-risk human papillomavirus (HR-HPV) infection is the major risk factor for cervical cancer, which remains a significant concern, particularly in low and middle-income countries due to the lack of effective treatment and preventive measures. Examining the prevalence and distribution of HR-HPV is key to designing or reformulating policies aimed at eliminating HPV-associated cancers.

Methods: A retrospective analysis was conducted using HR-HPV genotyping data from 9,524 women aged ≥18 years of the north-central region of Ecuador, who underwent cervical sampling either in cervical cancer prevention campaigns or during gynecological outpatient clinics, between January 2015 and August 2022. Samples were tested for HR-HPV using the cobas^® 4800 HPV Test. Infection rates and genotype distributions were assessed across years, age groups, and provinces. Multivariable logistic regression was conducted to identify independent factors associated with HR-HPV infections. Potential association profiles among genotypes were explored through Multiple correspondence analysis.

Results: The overall prevalence of HR-HPV was 26.87% [95% CI: 25.98, 27.77]. In particular, HPV 16 was found in 8.64% [95% CI: 8.08, 9.22] of the participants, HPV 18 in 2.85% [95% CI: 2.52, 3.20], and Other HR-HPV in 19.41% [95% CI: 18.62, 20.22]. Fluctuating prevalence trends during the study period were determined, with Other HR-HPV as the only category with a positive trend (aAPC: 3.44% [95% CI: 0.89, 6.05]; p < 0.01). The age-specific infection rate of HR-HPV showed a bimodal distribution, with the younger women (18-24 years old) harboring the highest rate. A second peak was identified in the postmenopausal group of 65-69 years old. Relative to Pichincha, Imbabura exhibited 50% higher odds ratio of HPV 16 infection (p < 0.001), while Santo Domingo de los Tsáchilas had 27% and 30% lower odds of Overall HR-HPV and Other HR-HPV infections, respectively (p < 0.01).

Conclusions: This study represents the largest-scale analysis on the epidemiology of HR-HPV in Ecuador. Given the high prevalence and positive trend of Other HR-HPV, our findings underscore the need for multivalent HPV vaccines. National screening strategies may consider screening of women over the age of 65 years when clinically indicated based on the patient history or physician judgment.

Clinical trial number: Not applicable.

Zoonotic viruses, which are pathogens naturally transmitted from animals to humans, pose a significant and evolving challenge to public health. Although most known zoonotic viruses do not exhibit the persistence typically necessary for viral oncogenesis, the potential cancer-causing effects of these infections remain unclear. Persistent infection, latency, or abortive replication within susceptible but non-permissive human cells may allow some animal-origin viruses to evade immune clearance, disrupt host cell signaling, and induce genomic instability-key features of cancer development. Evidence from both in vitro and in vivo studies indicates that certain animal viruses can enter human cells, integrate their genetic material, or express oncogenic proteins, even without completing full replication. These mechanisms resemble those of established human oncoviruses and suggest that, under specific host and environmental conditions, zoonotic viruses could contribute to neoplastic transformation. Given the increasing frequency of human-animal interactions through companionship, agriculture, wildlife trade, and food production, multidisciplinary research combining virology, oncology, and epidemiology is essential. Such efforts should focus on sensitive molecular detection, mechanistic studies, and population-based investigations to better understand the long-term cancer risks associated with zoonotic viral infections and to guide effective prevention strategies.

Background: Scarce data exist on host gene methylation in oropharyngeal squamous cell carcinomas (OPCs), which are caused by human papillomavirus (HPV) in approximately 40% of cases. We analyzed the methylation status of two host genes involved in cervical carcinogenesis, FAM19A4 and miR124-2, in formalin-fixed paraffin-embedded (FFPE) tissues of primary HPV-driven OPCs (i.e., HPV-positive and p16INK4A-positive), HPV-negative OPCs, head and neck (HN) squamous cell papillomas, and oral rinse-and-gargles (ORGs) from individuals without HN lesions.

Methods: A multiplex real-time methylation-specific PCR on bisulfite-converted DNA was employed (PreCursor-M+, Fujirebio). Hypermethylation for each target was expressed as negative/positive based on the ΔΔCt, as well as by the ΔΔCt ratio (2^-ΔΔCt).

Results: A total of 70 HPV-driven OPCs (66 HPV16+, 94.3%), 71 HPV-negative OPCs, 12 HN papillomas, and 20 ORGs were evaluated. Six of the 153 FFPE-purified DNA samples (3.9%) yielded invalid results. Hypermethylation for at least one target gene was observed in 56 of 69 valid HPV-driven OPCs (81.2%) and 33 of 67 valid HPV-negative OPCs (49.2%; p < 0.0001). None of the papillomas or ORGs were hypermethylated. HPV-driven OPCs showed a significantly higher methylation level compared with HPV-negative OPCs for both FAM19A4 (median ΔΔCt ratio 11.95 vs. 5.49; p = 0.0001) and miR124-2 (median ΔΔCt ratio 15.65 vs. 8.27; p < 0.0001).

Conclusions: Our findings indicate that FAM19A4/miR124-2 hypermethylation occurs exclusively in tumor samples and that methylation levels are significantly higher in HPV-driven OPCs than in HPV-negative OPCs.

There is growing evidence that Fusobacterium nucleatum, a Gram-negative anaerobic bacterium found in the gut and oropharynx, is a key player in the pathogenesis of colorectal cancer (CRC), by promoting tumor progression, immune evasion, and drug resistance. Despite the effectiveness of antibiotic regimens in reducing F. nucleatum abundance, concerns about antimicrobial resistance and gut dysbiosis limit the use of these drugs for a long period of time. Antimicrobial peptides (AMPs), bacteriophage therapy, and immune-based interventions all offer promising alternatives to conventional treatments. Checkpoint inhibitors and microbiome-based immunotherapy may also enhance antitumor immunity by alleviating F. nucleatum-induced immunosuppression. Furthermore, multimodal strategies, including dietary interventions and engineered probiotics, can help manage F. nucleatum-associated CRC holistically. It has been shown that probiotics can modulate gut microbiota composition and reduce F. nucleatum colonization by using strains of Lactobacillus and Bifidobacterium. This has led to improved outcomes for CRC patients by targeting this bacterium. In addition, preclinical evidence indicates that certain peptide-based antimicrobials can target F. nucleatum biofilms, though their specificity for pathogenic over commensal bacteria. Phage therapy, for instance, selectively targets the bacterium without harming others. But, to ensure efficacy and safety, clinical trials and mechanistic studies should be undertaken to optimize these therapeutic strategies. Understanding F. nucleatum's role in CRC and refining targeted interventions can help researchers develop innovative strategies to prevent and treat CRC. The purpose of this review is to examine current and emerging approaches to combating F. nucleatum in CRC, with a particular focus on probiotics, antibiotics, and alternative therapies.

Background: Methylation of host genes is promising for the triage of women with high-risk human papillomavirus (HR-HPV) infections. This study aimed to validate the potential value of Glycophorin C (GYPC) methylation (GYPC^m) in the early detection of cervical cancer.

Methods: We recruited HR-HPV-positive women at the hospital outpatient clinic between August and December 2023, using cytology triage. The remaining exfoliated cervical cells were subjected to GYPC^m testing. A total of 549 cases were finally included for analysis: 156 cervicitis, 303 cervical intraepithelial neoplasia (CIN)1, 49 CIN2, 37 CIN3, and 4 CC.

Results: The difference of GYPC^m ΔCp values between CIN1 and CIN2 was statistically significant in the pathology results of 549 participants (P < 0.001). The optimal threshold value of GYPC^m for detecting CIN2 + was 6.35. The GYPC^m adjusted ORs for CIN2 + and CIN3 + were 31.23 (95%CI: 16.53-58.99) and 34.68 (95%CI: 11.90-101.11), respectively. In all individuals, the sensitivity of GYPC^m for CIN2 + and CIN3 + was consistent with that of cytology (CIN2 + 83.3%; CIN3 + 90.2%), with higher specificity than that of cytology (CIN2 + 85.8 vs. 29.4%; CIN3 + 79.7 vs. 28.7%, all P < 0.001). The sensitivity and negative predictive value (NPV) of HPV16/18 combined GYPC^m for CIN3 + were not statistically different from those of HPV combined with cytology (sensitivity 95.1 vs. 97.6%, P = 0.317; NPV 99.4 vs. 99.0%, P = 0.613). The net reclassification improvement for HPV16/18 combined GYPC^m and its combined cytology to classify CIN2 + vs. < CIN2 was 48.8% (95%CI: 39.7-57.9%, P < 0.001), with a relative colposcopy referral rate of 50.1% (95%CI: 45.5-54.7%).

Conclusion: GYPC^m has a higher CIN2 + OR and higher specificity and positive predictive value than cytology in HR-HPV-positive women and is a potential molecular biomarker for triaging HR-HPV (+) to detect cervical (pre)cancer.

Objective: Human papillomavirus (HPV) infection is closely associated with the occurrence and development of cervical cancer. This study comprehensively investigates HPV infection and subtype distribution among women in Chengdu from 2019 to 2024, aiming to provide scientific evidence for screening, prevention, and optimization of HPV vaccination strategies against cervical cancer and related diseases.

Methods: Cervical exfoliated cell specimens from 65,130 female patients attended Sichuan Jinxin Xinan Women & Children Hospital from 2019 to 2024 were collected and detected 26 HPV gene subtypes using gene chip technology.

Results: Among the 65,130 women included in the study, 13,463 were HPV positive, with an overall detection rate of 20.67%. The single infection rate was 14.80%, and the multiple infection rate was 5.88%; the infection rates for pure HR-HPV, pure LR-HPV, and mixed infections were 13.86%, 3.90%, and 2.92%, respectively. The HPV detection rate was highest in those aged ≤ 20 years (46.01%) and among those aged > 60 years (35.37%), showing a bimodal distribution across ages. The top five HR-HPV subtypes detected were HPV52, 58, 16, 51, and 39, with infection rates of 3.71%, 2.81%, 2.56%, 1.83%, and 1.64%, respectively. The top three LR-HPV subtypes were HPV54, 42, and 40, with detection rates of 1.85%, 0.99%, and 0.93%, respectively. From 2019 to 2024, HPV detection showed a U-shaped trend, with a significant decrease in HPV16 detection rate and an increase in HPV42. Among other subtypes co-infected with the top five HR-HPV subtypes, HPV52 and HPV58 accounted for the highest proportion. After 2023, co-infections with LR-HPV increased.

Conclusion: During 2019-2024, the HPV infection rate among women in Chengdu was high with an increase in detection rates after 2023. The co-infection patterns of HR-HPV are complex. Infection rates are highest among women aged ≤ 20 years and > 60 years. Priority should be given to young women for vaccination. HPV screening should be strengthened for women across different age groups. Developing vaccines targeting locally prevalent HPV subtypes is crucial for reducing infection rates and preventing cervical cancer and other HPV-related diseases.

Precision medicine, which emphasizes individualized patient care rather than targeting a specific type of neoplasm, is becoming increasingly prevalent in oncology. Furthermore, the ability to combine multiple treatment modalities either concurrently or at different stages of the disease is enhancing both the safety and effectiveness of therapies. This, in turn, leads to improved patient outcomes, not only in terms of overall survival (OS) but also in physical well-being. Nevertheless, oncologic therapies can induce both local and systemic changes, as well as complications that are closely related to the type of treatment administered. Accurate interpretation of post-treatment imaging is therefore essential for timely and appropriate patient management.In this context, it is evident that radiologists specializing in oncology must be well-versed not only in the effects of various therapies but also in the different assessment criteria used to evaluate treatment efficacy accurately.The purpose of this article is to provide an overview of the various response evaluation criteria, beginning with conventional, size-based methods and progressing to functional approaches that rely on metabolic activity and Magnetic Resonance Imaging (MRI), while highlighting the respective advantages and limitations of each.