{"title":"Accuracy of POC testing systems for HPV screening: the importance of disease prevalence and characteristics of the screened population.","authors":"Paolo Giorgi Rossi, Guglielmo Ronco","doi":"10.1186/s13027-024-00629-9","DOIUrl":"10.1186/s13027-024-00629-9","url":null,"abstract":"<p><p>Infectious Agents and Cancer journal has recently launched a new collection of papers about \"Point-of-Care (POC) for HPV-related genital cancers\" putting together some interesting works on the accuracy of HPV tests for screening. This editorial initiative gave us the opportunity to reflect on the relations between accuracy measures, prevalence and characteristics of the tested population in the case of HPV-based screening. In screening test evaluation, we look at the clinical accuracy of the test as an intrinsic characteristic of the assay, which interacts with the characteristics of the population, the result being the screening performance. In the case of HPV testing, the clinical accuracy should be conceptualized in two steps, the analytical accuracy of the assay for HPV infection and the biological link between HPV infection and the target disease, i.e. the high-grade cervical intraepithelial neoplasia (hgCIN). This approach highlights that just a few false positive cases result from a lack of analytical specificity while most derive from women who have the infection but it did not progress to hgCIN. In addition, increasing prevalence of hgCIN results in relevant increases of PPV only if due or associated with exposures which increase the progression from infection to hgCIN or the duration of the latter; while an increase due to a higher prevalence of HPV infection would only marginally affect PPV. This approach may help in modelling the performance of HPV-based cervical screening.</p>","PeriodicalId":13568,"journal":{"name":"Infectious Agents and Cancer","volume":"19 1","pages":"65"},"PeriodicalIF":3.1,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11662695/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Elizabeth G Sumiec, Zhe Yang Yim, Hannah Mohy-Eldin, Belinda Nedjai
{"title":"The current state of DNA methylation biomarkers in self-collected liquid biopsies for the early detection of cervical cancer: a literature review.","authors":"Elizabeth G Sumiec, Zhe Yang Yim, Hannah Mohy-Eldin, Belinda Nedjai","doi":"10.1186/s13027-024-00623-1","DOIUrl":"10.1186/s13027-024-00623-1","url":null,"abstract":"<p><p>Cervical cancer (CC) is a preventable disease and treatable cancer. Most of the new cases and deaths from CC occur in Low- and Middle-Income Countries (LMICs) due to cultural and systematic barriers leading to low CC screening uptake. In recent years, self-sampling has been proposed as a method to increase CC screening uptake and is slowly being implemented into screening programmes worldwide. Simultaneously, DNA methylation has been proposed as a novel biomarker that could be used for the triage of self-collected samples that test positive for high-risk types of Human Papillomavirus (HPV). In this paper, we conducted a literature review of studies assessing the efficacy of DNA methylation markers to detect Cervical Intraepithelial Neoplasia (CIN) in self-collected cervicovaginal swabs or urine (2019-2024). Our review showed that, of the available data, DNA methylation together with self-sampling could perform as well as cytology in the detection of CIN as well as improve uptake of CC screening and reduce loss to follow up, especially in LMICs. However, more data is still needed to understand which methylation tests are most efficacious. Future studies should assess the full potential of DNA methylation and self-sampling in large, diverse screening cohorts.</p>","PeriodicalId":13568,"journal":{"name":"Infectious Agents and Cancer","volume":"19 1","pages":"62"},"PeriodicalIF":3.1,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11654125/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142854100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anqi Xie, Hengjie Wang, Jingchen Huang, Minmin Sun, Lin Chen
{"title":"miR-3191 promotes the proliferation and metastasis of hepatocellular carcinoma via regulating PAK6.","authors":"Anqi Xie, Hengjie Wang, Jingchen Huang, Minmin Sun, Lin Chen","doi":"10.1186/s13027-024-00628-w","DOIUrl":"10.1186/s13027-024-00628-w","url":null,"abstract":"<p><strong>Background/aims: </strong>microRNAs (miRNAs) contribute to tumorigenesis, progression and drug resistance of hepatocellular carcinoma (HCC). miR-3191 is a newly discovered miRNA, and its function and mechanism of action in biological processes and diseases are not completely understood.</p><p><strong>Methods: </strong>miR-3191 expression is determined via quantitative real-time polymerase chain reaction. Knockdown and overexpression of miR-3191 influence the proliferation and metastasis of HCC cells, which is measured by Cell Counting Kit-8 assay, Colony Formation assay and Cell metastasis assay. Protein expression is estimated by Western blot. The interplay between miR-3191 and target is validated by dual-luciferase reporter assay.</p><p><strong>Results: </strong>Here, we show that miR-3191 is upregulated in HCC tissues and associated with poor prognosis of HCC patients. Mechanistically, p21-activated protein kinase 6 (PAK6) was identified as a direct target of miR‑3191 in HCC. PAK6 knockdown partially recovered interference of miR‑3191‑induced decrease in cell proliferation and invasion. The accuracy of HCC patient prognosis could be improved by employing a combination of miR-3191 and PAK6 values.</p><p><strong>Conclusions: </strong>miR-3191 promotes the proliferation and metastasis of HCC cells via targeting PAK6 and may serve as a prognostic biomarker and potential therapeutic target.</p>","PeriodicalId":13568,"journal":{"name":"Infectious Agents and Cancer","volume":"19 1","pages":"64"},"PeriodicalIF":3.1,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11654304/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142854064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Prevalence of HPV in anal cancer: exploring the role of infection and inflammation.","authors":"Fatemeh Ebrahimi, Reyhaneh Rasizadeh, Sajjad Jafari, Hossein Bannazadeh Baghi","doi":"10.1186/s13027-024-00624-0","DOIUrl":"10.1186/s13027-024-00624-0","url":null,"abstract":"<p><p>Anal cancer incidence is rising globally, driven primarily by human papillomavirus (HPV) infection. HPV, especially high-risk types 16 and 18, is considered a necessary cause of anal squamous cell carcinoma. Certain populations like people living with HIV, men who have sex with men, inflammatory bowel disease patients, smokers, and those with compromised immunity face elevated risk. Chronic inflammation facilitates viral persistence, cell transformation, and immune evasion through pathways involving the PD-1/PD-L1 axis. HIV coinfection further increases risk by impairing immune surveillance and epithelial integrity while promoting HPV oncogene expression. Understanding these inflammatory processes, including roles of CD8 + T cells and PD-1/PD-L1, could guide development of immunotherapies against anal cancer. This review summarizes current knowledge on inflammation's role in anal cancer pathogenesis and the interplay between HPV, HIV, and host immune factors.</p>","PeriodicalId":13568,"journal":{"name":"Infectious Agents and Cancer","volume":"19 1","pages":"63"},"PeriodicalIF":3.1,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11654204/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142854096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dongmei Li, Zhichao Wang, Yan Liu, Meiyuan Zhou, Bo Xia, Lin Zhang, Keming Chen, Yong Zeng
{"title":"Assessing the risk of high-grade squamous intraepithelial lesions (HSIL+) in women with LSIL biopsies: a machine learning-based study.","authors":"Dongmei Li, Zhichao Wang, Yan Liu, Meiyuan Zhou, Bo Xia, Lin Zhang, Keming Chen, Yong Zeng","doi":"10.1186/s13027-024-00625-z","DOIUrl":"10.1186/s13027-024-00625-z","url":null,"abstract":"<p><strong>Objective: </strong>This study aims to analyze factors associated with the missed diagnosis of high-grade squamous intraepithelial lesions (HSIL+) in patients initially diagnosed with low-grade squamous intraepithelial lesions (LSIL) through colposcopic biopsy and to develop a predictive model for assessing the risk of missed HSIL+.</p><p><strong>Methods: </strong>We conducted a retrospective analysis of 505 patients who underwent loop electrical excision procedure (LEEP) following an LSIL diagnosis by colposcopic biopsy. Logistic regression was used to identify demographic and pathological parameters associated with missed diagnoses of HSIL+. Additionally, several machine learning methods were employed to construct and assess the performance of the risk prediction models.</p><p><strong>Results: </strong>The overall rate of missed diagnoses for HSIL+ was 15.2%. Independent risk factors identified were HPV16/18 infection (OR 2.071; 95% CI 1.039-4.127; p = 0.039), TCT ≥ ASC-H (OR 4.147; 95% CI 1.392-12.355; p = 0.011), TZ3 (OR 1.966; 95% CI 1.003-3.853; p = 0.049) and Colposcopic impression G2 (OR 3.627; 95% CI 1.350-9.743; p = 0.011). Among the models tested, the Decision Tree algorithm demonstrated superior performance with an accuracy of 94.7%, sensitivity of 80.0%, specificity of 96.9%, and an area under the curve (AUC) of 0.936 in the validation set.</p><p><strong>Conclusion: </strong>Key independent risk factors for the missed diagnosis of HSIL in patients with LSIL include HPV16/18 infection, TCT ≥ ASC-H, TZ3, and colposcopic impression G2. The Decision Tree model offers a cost-effective, reliable, and clinically valuable tool for accurately predicting the risk of missed diagnosis of HSIL+, facilitating early intervention and management.</p>","PeriodicalId":13568,"journal":{"name":"Infectious Agents and Cancer","volume":"19 1","pages":"61"},"PeriodicalIF":3.1,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11622471/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142785453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tianfei Yu, Jinyong Xia, Haichang Yin, Nana Yi, Lanlan Zhang, Ming Li
{"title":"Enhancing the robustness of Mendelian randomization studies: lessons from a two-sample analysis of viral infections and colorectal cancer.","authors":"Tianfei Yu, Jinyong Xia, Haichang Yin, Nana Yi, Lanlan Zhang, Ming Li","doi":"10.1186/s13027-024-00626-y","DOIUrl":"10.1186/s13027-024-00626-y","url":null,"abstract":"<p><p>This Matters Arising article critically examines the study \"Genetic susceptibility association between viral infection and colorectal cancer risk: a two-sample Mendelian randomization analysis\" by Li et al., highlighting both its contributions and methodological limitations. Their study employed two-sample Mendelian randomization (MR) to explore potential causal links between viral infections and colorectal cancer (CRC), identifying significant associations with infections such as herpes simplex virus and measles. However, several aspects of the methodology warrant scrutiny, including the relaxation of instrumental variable selection thresholds, the handling of potential pleiotropy, and the interpretation of biologically implausible findings. While leveraging advanced MR techniques such as MR-RAPS, cML, ConMix, and dIVW to address challenges like pleiotropy and weak instruments, the study encountered issues related to heterogeneity, insufficient exploration of biological plausibility, and a lack of detailed reporting on instrumental variable (IV) selection and preprocessing. This Matters Arising calls for more rigorous sensitivity analyses, improved transparency in IV selection criteria and harmonization of genome-wide association study (GWAS) datasets, particularly in addressing differences between self-reported and clinically diagnosed infections. Additionally, the Matters Arising article calls for a deeper exploration of biological mechanisms, such as the role of immune modulation and inflammation, to better interpret the observed associations. By addressing these limitations, future MR studies can enhance methodological rigor, improve reproducibility, and provide more robust insights into the causal pathways linking viral infections to CRC risk.</p>","PeriodicalId":13568,"journal":{"name":"Infectious Agents and Cancer","volume":"19 1","pages":"60"},"PeriodicalIF":3.1,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11619104/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142785456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jun Wang, Godwin Imade, Alani S Akanmu, Jonah Musa, Rose Anorlu, Yinan Zheng, Olga Garcia-Bedoya, Gloria I Sanchez, Jerome Belinson, Kyeezu Kim, Mamoudou Maiga, Demirkan B Gursel, Atiene S Sagay, Folasade T Ogunsola, Robert L Murphy, Lifang Hou
{"title":"Analytic performance of ScreenFire HPV RS assay Zebra BioDome format and its potential for large-scale population HPV screening.","authors":"Jun Wang, Godwin Imade, Alani S Akanmu, Jonah Musa, Rose Anorlu, Yinan Zheng, Olga Garcia-Bedoya, Gloria I Sanchez, Jerome Belinson, Kyeezu Kim, Mamoudou Maiga, Demirkan B Gursel, Atiene S Sagay, Folasade T Ogunsola, Robert L Murphy, Lifang Hou","doi":"10.1186/s13027-024-00622-2","DOIUrl":"10.1186/s13027-024-00622-2","url":null,"abstract":"<p><strong>Background: </strong>Easy-to-use, rapid, scalable, high-throughput, and cost-effective HPV tests are urgently needed for low-resource settings. Atila Biosystems' high-throughput, cost-effective, and clinically validated ScreenFire HPV Risk Stratification (RS) assay identifies 13 high risk HPV (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). The current standard format is subject to laboratory contamination, which is common for any molecular PCR test. To overcome this drawback, Atila has recently upgraded it into an innovative, contamination-free Zebra BioDome format. The contamination-free feature makes this novel assay format more suitable for large-scale community- and population-based cervical screening. This study evaluated the analytical performance of the Zebra BioDome format.</p><p><strong>Methods: </strong>We conducted a study to test the analytical performance of Zebra Biodome format in comparison to the results of using the ScreenFire HPV RS assay standard format on Biorad CFX-96 real-time PCR instrument. We used overall agreement rate and unweighted kappa value to compare the performance.</p><p><strong>Results: </strong>The overall agreement for detection of hrHPV was 96.0% with unweighted kappa value 0.94 (95% confidence interval: 0.90-0.98). The agreement rates between hrHPV genotype 16 and risk stratification genotype group (HPV18/45, HPV31/33/35/52/58, and HPV51/59/39/56/68) were all > 97.5%.</p><p><strong>Conclusion: </strong>The innovative ScreenFire HPV RS assay Zebra BioDome format produced highly concordant results with the standard format. The shared features by the two assay formats, such as easy-to-use, high throughput, cost-appropriate, and no requirements for DNA extraction. The unique contamination-prevention feature along with no requirement of preparation of reagents make the Zebra BioDome format more suitable for large-scale HPV screening to reduce global cervical cancer burden.</p>","PeriodicalId":13568,"journal":{"name":"Infectious Agents and Cancer","volume":"19 1","pages":"59"},"PeriodicalIF":3.1,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11606105/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142755078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The epidemic of human papillomavirus virus-related oropharyngeal cancer: current controversies and future questions.","authors":"Allen M Chen","doi":"10.1186/s13027-024-00616-0","DOIUrl":"10.1186/s13027-024-00616-0","url":null,"abstract":"<p><p>The incidence of human papillomavirus (HPV) associated oropharyngeal cancer has increased to epidemic-like proportions in the United States and other industrialized nations. While significant progress has been made in the understanding of this disease with respect to its underlying biology and clinical behavior, numerous questions persist regarding treatment. It is now firmly established that patients with HPV-positive oropharyngeal cancer have a significantly improved prognosis as a result of their exquisite radiosensitivity compared to their HPV-negative counterparts and thus can be targeted with de-escalated approaches using reduced doses of radiation and/or chemotherapy. The fundamental goal of de-escalation is to maintain the high cure and survival rates associated with traditional approaches while reducing the incidence of both short- and long-term toxicity. Although the exact reason for the improved radiosensitivity of HPV-positive oropharyngeal carcinoma is unclear, prospective studies have now been published demonstrating that de-escalated radiation can successfully maintain the high rates of cure and preserve quality of life for appropriately selected patients with this disease. However, the selection criteria and specific means for de-escalation remain uncertain, and paradigms continue to evolve. Given that HPV-positive oropharyngeal cancer is increasingly recognized as a public health problem, the search for answers to many of these provocative questions has important societal implications and is the subject of this review.</p>","PeriodicalId":13568,"journal":{"name":"Infectious Agents and Cancer","volume":"19 1","pages":"58"},"PeriodicalIF":3.1,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11606068/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142750720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Karoline Andersen, Paul Vinu Salachan, Michael Borre, Benedicte Ulhøi, Magnus Stougaard, Karina Dalsgaard Sørensen, Torben Steiniche
{"title":"Highly sensitive deep panel sequencing of 27 HPV genotypes in prostate cancer biopsies results in very low detection rates and indicates that HPV is not a major etiological driver of this malignancy.","authors":"Karoline Andersen, Paul Vinu Salachan, Michael Borre, Benedicte Ulhøi, Magnus Stougaard, Karina Dalsgaard Sørensen, Torben Steiniche","doi":"10.1186/s13027-024-00619-x","DOIUrl":"10.1186/s13027-024-00619-x","url":null,"abstract":"<p><strong>Background: </strong>Human papillomavirus (HPV) has been proposed to contribute to the carcinogenesis of prostate cancer. However, previous studies have yielded conflicting results. This study aims to add useful information to the ongoing discussion concerning the association between HPV infection and prostate cancer.</p><p><strong>Methods: </strong>We used two high-throughput next-generation sequencing (NGS) approaches to detect HPV RNA in malignant and adjacent normal (AN) prostate tissue (cohorts 1 and 2) and HPV DNA from carcinogenic and probably/possibly carcinogenic-classified HPV types (cohort 3) in malignant prostate, AN prostate, and benign prostatic hyperplasia (BPH) tissues.</p><p><strong>Results: </strong>In total, 0% (cohort 1: 0/83, cohort 2: 0/16) of the malignant prostate tissue samples and 0% (cohort 1: 0/23, cohort 2: 0/8) of the AN prostate tissue samples were positive for HPV RNA. A total of 8.3% (1/12) of the BPH samples, 0% (0/28) of the AN samples, and 0.8% (1/132) of the malignant prostate samples were positive for HPV16 DNA. However, the normalized read count of the HPV16-positive malignant sample was close to the cut-off. In addition, no other carcinogenic-classified HPV types were detected in any of the BPH, AN, or malignant prostate tissue samples.</p><p><strong>Conclusion: </strong>Our study does not support HPV infection as a major contributor to the etiology of prostate cancer.</p>","PeriodicalId":13568,"journal":{"name":"Infectious Agents and Cancer","volume":"19 1","pages":"57"},"PeriodicalIF":3.1,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11566718/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142619241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Insight into the mechanisms regulating liver cancer stem cells by hepatitis B virus X protein.","authors":"Xiaocui Li, Delong Kong, Wei Hu, Kuiyang Zheng, Hongjuan You, Renxian Tang, Fanyun Kong","doi":"10.1186/s13027-024-00618-y","DOIUrl":"10.1186/s13027-024-00618-y","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) is a heterogeneous disease with high recurrence and mortality. It is well known that a large proportion of HCCs are caused by hepatitis B virus (HBV) infection. In particular, the HBV X protein (HBX), a multifunctional molecule produced by the virus, plays a leading role in hepatocarcinogenesis. However, the molecular mechanisms underlying HBX-mediated HCC remain not fully elucidated. Recently, liver cancer stem cells (LCSCs), a unique heterogeneous subpopulation of the malignancy, have received particular attention owing to their close association with tumorigenesis. Especially, the modulation of LCSCs by HBX by upregulating CD133, CD44, EpCAM, and CD90 plays a significant role in HBV-related HCC development. More importantly, not only multiple signaling pathways, including Wnt/β-catenin signaling, transforming growth factor-β (TGF-β) signaling, phosphatidylinositol-3-kinase (PI-3 K)/AKT signaling, and STAT3 signaling pathways, but also epigenetic regulation, such as DNA and histone methylation, and noncoding RNAs, including lncRNA and microRNA, are discovered to participate in regulating LCSCs mediated by HBX. Here, we summarized the mechanisms underlying different signaling pathways and epigenetic alterations that contribute to the modulation of HBX-induced LCSCs to facilitate hepatocarcinogenesis. Because LCSCs are important in hepatic carcinogenesis, understanding the regulatory factors controlled by HBX might open new avenues for HBV-associated liver cancer treatment.</p>","PeriodicalId":13568,"journal":{"name":"Infectious Agents and Cancer","volume":"19 1","pages":"56"},"PeriodicalIF":3.1,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11555838/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142619421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}