Infectious Agents and Cancer最新文献

Purpose: This study aims to explore the contrasting trends of decreasing cervical cancer (CC) rates among women and increasing oropharyngeal cancer (OPC) rates among men.

Methods: The analysis examines public health initiatives, including CC screening programs and HPV vaccination efforts, alongside the changing epidemiology of OPC.

Results: Declines in CC incidence are attributed to improved screening and HPV vaccination. Conversely, OPC rates are rising among men, linked primarily to HPV infection and lack of established screening programs. Data indicate a higher OPC burden in men compared to CC in women in several countries.

Conclusion: Addressing the rising OPC trend requires a multifaceted approach, including gender-neutral HPV vaccination, the development of OPC screening methods, and increased public awareness. Sustained efforts in HPV-related cancer prevention are crucial to mitigate these opposing trends.

Background: Gastric cancer (GC) is a very aggressive malignant tumor of the digestive system. Previous studies have shown that N-acetyltransferase 10 (NAT10) can regulate the N4-acetylcytidine (ac4C) modification of downstream mRNAs through certain pathways to promote the progression of various tumors. However, reports on the regulatory effects of NAT10 on GC are rare. This study aimed to explore the potential mechanism by which NAT10 regulated GC progression.

Methods: Clinical samples were used to study the correlation between NAT10 expression and poor prognosis in patients with GC by univariate analysis and multivariate analysis. In vitro and in vivo assays were performed to assess the effects of NAT10 and Tenascin C (TNC) on the malignant biological behaviors of GC cells. Acetylated RNA immunoprecipitation sequencing was conducted to explore the role of NAT10 in ac4C modification in GC. mRNA stability and translation efficiency assays were performed to investigate the effect of changes in NAT10 expression on its target TNC.

Results: Analysis of clinical samples revealed that NAT10 expression was abnormally elevated and positively correlated with TNC expression in GC, and increased NAT10 expression led to poor overall survival. In vitro and in vivo experiments revealed that high NAT10 expression promoted the invasive and proliferative capacity of GC cells. Rescue experiments suggested that TNC played an important role in the above process. Mechanistically, the acetylation-based RNA immunoprecipitation sequencing and acetylated RNA immunoprecipitation qPCR results indicated that NAT10 regulated the level of ac4C modification by binding to specific regions in TNC mRNA, increasing mRNA stability and translation, upregulating TNC expression, further activating the TNC/Akt/TGF-β1 positive feedback loop.

Conclusions: In summary, our results reveal that NAT10 plays a critical role in GC development by affecting TNC mRNA stability and translation efficiency, which ultimately activates the TNC/Akt/TGF-β1 positive feedback loop. This study is expected to provide a novel target and theoretical basis for improving the diagnosis and treatment of GC.

Objective: Although hepatitis B virus (HBV) infection was regarded as a risk factor for liver cancer, the association of HBV infection with gastric cancer (GC) is unclear. In this study, we aim to assess the association of HBV infection with the risk of GC and explore the interaction between HBV infection and other risk factors.

Methods: A case-control study was conducted and 409 GC cases and 1275 healthy controls were enrolled in Fujian province, China. Serum hepatitis B surface antigen (HBsAg) was measured and epidemiological data were collected. The association between HBV infection and GC risk was analyzed using logistic regression and meta-analysis method was employed to make estimates more conservative. Meanwhile, multiplicative and additive models were used to explore the interaction between HBV infection and other risk factors.

Results: The prevalence of serum HBsAg positivity was 13.20% among GC cases and 6.20% among controls. Compared to HBsAg-negative subjects, the adjusted odds ratios (OR) for HBsAg positive were 3.30 [95% confidence interval (CI): (1.84-5.91)]. Compared to HBsAg-negative never smokers, the adjusted OR was 2.00 (95%CI: 1.19-3.34) for HBsAg-negative ever smokers,4.27 (95%CI: 1.97-9.26) for HBsAg-positive never smokers, and 4.73 (95%CI: 1.85-12.08) for HBsAg-positive ever smokers. These evidences indicated super-additive [API (95%CI): 0.78 (0.67-0.90), S (95%CI): 5.45 (3.26-9.08)] between HBV infection and tobacco smoking. No interaction between HBV infection and alcohol drinking was found on the risk of GC.

Conclusions: HBV infection increased the risk of GC, and tobacco smoking and HBV infection may positively interact in the development of GC.

Background: Despite the success of antiretroviral therapy in HIV treatment, cervical cancer remains a leading malignancy in HIV-infected women. Additionally, co-infection by HIV and HPV further accelerates cervical cancer development. There are limited studies on the role of host somatic variations in HIV infected and HIV-negative women with cervical cancer. Therefore, this study aimed to investigate and compare host somatic genetic variation in cervical biopsies obtained from HIV infected and HIV-negative women with cervical intraepithelial neoplasia 3 to understand the genomic landscape. The distribution of HPV types was also investigated between HIV infected and HIV-negative women.

Methods: The project used an age-matched case-control study utilizing archived cervical biopsies from 88 women (44 HIV infected, 44 HIV-negative) attending Groote Schuur Hospital Cancer Clinic between 2020 and 2022. HPV infection and type were confirmed using the Anyplex™ II HPV28 Detection kit. Six hotspot regions in the four commonly mutated genes (TP53, PIK3CA, PTEN, and EGFR) in cervical cancer were genotyped using PCR and Sanger Sequencing. Variant pathogenicity was assessed using SIFT, Polyphen-2, and ClinVar tools.

Results: The median age was 37 years (IQR: 34-41) for HIV infected women and 35 years (IQR:32- 43) for HIV-negative women. Significantly more HIV-negative women (51% vs. 12%) reported tobacco smoking (p < 0.0001), menstruation irregularities (74% vs. 35%; p = 0.005), and contraception usage (77% vs. 59%; p = 0.019), when compared to their HIV-infected counterparts. Common HPV types identified were HPV16 (n = 43/88, 49%), HPV35 (n = 12/88, 14%), and HPV58 (n = 10/88, 11%). A total of 232 genetic variants were reported. HIV infected women had a significantly higher (p = 0.0406) burden of pathogenic variants (31%) compared to the HIV-negative (15%). The spectrum of observed mutations included stop-gain, missense, synonymous, and intronic changes. Most of the stop gain mutations in TP53 and PIK3CA were reported among HIV infected women (n = 4/5), compared to HIV-negative women (n = 1/5). Damaging variants were more prevalent in women under 50 in both cohorts. We also report on rare HPV subtypes currently not included in the diagnostic HPV test kits in this cohort (HPV 82, 42, 43 and 53).

Conclusion: HIV-infection status and age appear to be risk factors for higher burden of pathogenic mutations in genes that predispose to cervical cancer. Mutation profiles in PIK3CA and TP53 genes could be biomarkers of cervical cancer progression but more studies are needed.

The increasing incidence and mortality rates of HPV-positive cancers, particularly HPV-positive head and neck cancer, in recent years have emphasized the pressing need for more efficacious treatment options. Recent studies have elucidated the molecular distinctions between HPV-positive and HPV-negative cancers, which are crucial for developing precise and effective therapeutic strategies. This review updates the most recent findings on the molecular variances between HPV-positive and HPV-negative cancers, evaluates current treatments for HPV-positive cancers, and summarizes emerging frontiers in HPV-targeted therapies aimed at developing more effective and precise interventions against these cancers.

Several high-risk types of human papillomaviruses (HPVs) are associated with cervical cancer and other malignancies. Despite the tremendous success of marketed prophylactic HPV vaccines for the past 18 years, cervical cancer remains a significant global challenge. A nearly 10% increase in new cervical cancer cases worldwide from 2020 to 2022 underscores the urgent need for enhanced vaccination efforts. Current HPV vaccines, including Cervarix®, Gardasil®, Gardasil®9, Cecolin®, and Walrinvax® utilize VLP (virus-like particle) structures and have demonstrated significant efficacy. However, challenges such as type-limited coverage, cold-chain requirements, and affordability emphasize the critical need for further research and development of novel HPV vaccines. Some investigational vaccines, for instance, those using VLPs to carry protective antigens with broader coverage across different viral types, show promise for the future of cervical cancer prevention. Realizing this hope and making further progress still depend on the dedication and innovation of the scientists and authorities involved. This review focuses on both approved and investigational preventive vaccines, including also those designed for simultaneous prevention and therapy. Clinical trials are briefly reviewed, and potential strategies to advance vaccination against HPV-induced cervical cancer are summarized. This review emphasizes approaches that require further investigation in the future.

Cervical cancer is a significant public health concern, disproportionately affecting women in less developed regions due to limited access to screening and vaccination programs. Despite advancements in cervical cancer prevention and treatment, there remains a need for efficient and cost-effective diagnostic tools. This study aimed to develop a multiplex real-time PCR assay to rapidly and accurately identify 15 human papillomavirus (HPV) genotypes.The primary objective was to design a screening method capable of simultaneously detecting HPV types 16 and 18, which account for over 70% of cervical cancers, as well as other clinically relevant high-risk and probable/possible high-risk. To validate the assay's performance, we compared its results with those obtained using the commercially available INNO-LiPA HPV Genotyping Extra II Assay kit (FujireBio, Tokyo, Japan). The developed assay successfully identified 15 HPV genotypes in a single reaction. Analysis of 150 positive and 40 negative clinical samples demonstrated excellent concordance between the two assays. The in-house real-time PCR test exhibited a clinical sensitivity of 98% and a clinical specificity of 100%, indicating its reliability and accuracy for HPV genotyping. The multiplex real-time PCR assay is a cost-effective and efficient tool for HPV screening, detecting multiple genotypes simultaneously. It enhances screening efficiency and accuracy, improving early detection and management of HPV-related diseases.

Background: Breast cancer is a major global health problem worldwide, affecting more than 2.25 million women annually. The disease is influenced by various factors, including some viruses, gender, age, and family history. This study aimed to conducting a comprehensive systematic review and meta-analysis of existing studies on the polyomaviruses in breast cancer.

Methods: This systematic review and meta-analysis aimed to provide an evidence-based analysis of the relationship between polyomaviruses and breast cancer. The global online databases were used to identify relevant studies published from 2000 to July 2024. The quality of each article was assessed using the Newcastle-Ottawa Scale (NOS) checklist. Data analysis was performed using STATA software, and standard errors of prevalence were calculated using the binomial distribution formula. Heterogeneity of study results was evaluated using the I-square and Q index, while publication bias was examined using the Begg's test. A random effects model was used to determine prevalence rates, and a forest plot diagram was used to present results with 95% confidence intervals. The Trim and Fill test was applied to estimate publication bias, and sensitivity analysis was performed to assess the influence of individual studies on the overall estimate.

Results: Nine studies met the inclusion and exclusion criteria for this analysis. In this study, the prevalence of BKV, JCV, HPyV7, KIV, WUV, SV40, and TSV in breast cancer patients was found to be 0%. By combining the results of these studies, the prevalence of PyV, MCV, and HPyV6 in breast cancer patients was 11%, 4%, and 1%, respectively.

Conclusion: The meta-analysis presented here provides an exhaustive overview of the current literature on the prevalence of polyomaviruses in breast cancer patients. Findings indicate a potentially stronger association between PyV and breast cancer than other human polyomaviruses.

Background and aim: Human papillomavirus (HPV) is a major contributor to sexually transmitted infections, especially common in sexually active populations. Although the majority of HPV infections resolve naturally, certain cases can develop into different types of cancer. This study focused on evaluating the prevalence and distribution of HPV genotypes across males and females of different age groups who visited a laboratory in Urmia, Iran.

Materials and methods: Samples from the genital area were obtained from participants in the study. DNA extraction was performed using the Favorgen extraction kit (Favorgen, Taiwan), followed by genotyping through Real-Time PCR. Genotypes were determined using the MehrViru HPV genotyping kit (MehrViru, Iran). Additionally, demographic details, including age, were analyzed in conjunction with the statistical virological data.

Results: Between 2022 and 2023, a total of 447 individuals, including both referred and routine visitors, attended the laboratory, comprising 431 females and 16 males. Of these, 195 tested positive for HPV, resulting in an overall prevalence rate of 43.6%. Among the positive cases, 90 individuals (46.2%) were infected with a single HPV genotype, while 105 cases (53.8%) had multiple genotype infections. The most common genotypes identified were HPV-6 (41.0%), HPV-16 (15.4%), HPV-56 (10.8%), and HPV-90 (10.8%). The least genotype identified was HPV-43, which was detected in 5 cases (2.6%). Additionally, our analysis revealed that women under 30 who tested positive were predominantly infected with the LR genotype, a pattern also seen in the four men in the same age group, all of whom were infected with the LR genotype.

Conclusion: Our findings underscore the significant presence of HPV among both females and males visiting the laboratory in Urmia, particularly in individuals under 30 years old. The identification of HPV-6 and HPV-16 as the most prevalent genotypes highlights the importance of age-specific intervention strategies. Although vaccination programs cover HPV-6 and HPV-16, HPV-56 is not included, which underscores the need for comprehensive screening and preventive measures to address the potential long-term impacts of HPV-related diseases.

Background: This study investigates the underlying mechanism of circKIAA1429 (hsa_circ_0084922) in hepatocellular carcinoma (HCC) progression.

Methods: circKIAA1429, SETD1A, NAP1L3, and GLIS2 expressions in HCC cells were detected by RT-qPCR or western blot. The stability of circKIAA1429 was tested after treatment with actinomycin D and Rnase R enzyme. circKIAA1429 expression was knocked down, followed by detection of cell proliferation, apoptosis, and migration/invasion using CCK-8, flow cytometry, and transwell. RIP and RNA pull-down were performed to validate the binding between circKIAA1429 and SETD1A, while ChIP analysis determined the enrichment of SETD1A and H3K4me3 or H3K27me3 on GLIS2 or NAP1L3 promoter. A nude mouse xenograft tumor model was establish to test the effect of circKIAA1429 on tumorigenicity.

Results: circKIAA1429 and NAP1L3 were highly expressed in HCC cells, while GLIS2 was poorly expressed. Knockdown of circKIAA1429 repressed cell proliferation/invasion/migration and facilitated apoptosis. Mechanistically, circKIAA1429 directly interacted with SETD1A to reduce the enrichment of SETD1A and H3K4me3 or H3K27me3 on GLIS2 or NAP1L3 promoter, thus diminishing GLIS2 expression and elevating NAP1L3 expression. In vivo, circKIAA1429 promotes tumorigenesis via GLIS2/NAP1L3.

Conclusion: circKIAA1429 interacts with SETD1A to inhibit the enrichment of H3K4me3 and H3K27me3 on GLIS2 or NAP1L3 promoter, thus inhibiting/promoting the expression of GLIS2/NAP1L3 and accelerating the progression of HCC.