Infectious Agents and Cancer最新文献

{"title":"Acquired epidermodysplasia verruciformis presenting as isolated genital hypopigmentation in a renal transplant recipient: a rare case report.","authors":"Amir Hossein Barjasteh, Abedeh Aslami, Hanieh Latifi, Masoumeh Hoseininezhad, Naser Tayyebi Meibodi, Reyhaneh Fazeli, Amirali Reihani","doi":"10.1186/s13027-026-00774-3","DOIUrl":"10.1186/s13027-026-00774-3","url":null,"abstract":"<p><p>Epidermodysplasia verruciformis (EV) is a rare genodermatosis resulting from mutations in the EVER1/EVER2 genes, that increase vulnerability to beta-human papillomavirus (β-HPV) infection. The acquired form (AEV) develops in immunocompromised individuals, particularly organ transplant recipients, and typically manifests as pityriasis versicolor-like macules on sun-exposed areas. However, lesions confined to non-sun-exposed regions, especially the genitalia, are exceedingly uncommon and may be misdiagnosed. We report the case of a 38-year-old woman, nine years post-renal transplantation and on long-term triple immunosuppressive therapy (cyclosporine, mycophenolate mofetil, and prednisolone), who presented with progressive, non-pruritic, well-demarcated hypopigmented macules localized exclusively to her labia majora and mons pubis. The lesions were initially misdiagnosed and unsuccessfully treated as tinea versicolor. A skin biopsy revealed histopathologic features characteristic of EV, including enlarged keratinocytes with blue-gray cytoplasm and perinuclear halos and koilocytotic changes. This case emphasizes that AEV should be considered in the differential diagnosis of genital hypopigmented lesions in immunosuppressed patients. Accurate histopathologic evaluation is crucial for timely recognition, appropriate management, and ongoing surveillance to prevent missed malignant transformation.</p>","PeriodicalId":13568,"journal":{"name":"Infectious Agents and Cancer","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13505068/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148264436","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":"Single-cell transcriptomics and machine learning unveil liquid-liquid phase separation-related biomarkers in HPV-positive cervical cancer.","authors":"Yiru Chen","doi":"10.1186/s13027-026-00768-1","DOIUrl":"https://doi.org/10.1186/s13027-026-00768-1","url":null,"abstract":"<p><strong>Background: </strong>Liquid-liquid phase separation (LLPS) dysregulation is a key driver of oncogenesis, yet its specific role in HPV-positive cervical cancer remains undefined. We hypothesized that HPV-positive tumors exploit distinct LLPS mechanisms to evade nucleolar stress surveillance, offering a novel avenue for biomarker discovery.</p><p><strong>Methods: </strong>We analyzed 70,519 single-cell transcriptomes across four histological conditions (Normal/Cancer, HPV+/-) to interrogate a curated panel of 120 LLPS-related genes. Our analytical framework integrated multi-tiered differential expression modeling with Random Forest classification to identify transformation-specific signatures.</p><p><strong>Results: </strong>Analysis revealed a significant Cancer-HPV interaction effect characterized by the robust suppression of ribosomal proteins RPL5 and RPL11 (log₂FC ≈ - 3.4) specifically in HPV-positive cancer. Machine learning validation confirmed these genes as the top predictors (Variable Importance: RPL5 81.4%, RPL11 76.9%). The integrated model achieved 69.7% classification accuracy, predicting HPV-positive malignancy with a posterior probability of 78.4%.</p><p><strong>Conclusions: </strong>This study identifies a unique, HPV-specific suppression of the LLPS-regulators RPL5 and RPL11, mechanistically linking viral carcinogenesis to the evasion of ribosomal stress pathways. By integrating single-cell transcriptomics with machine learning, we present a novel, transformation-specific biomarker panel that distinguishes HPV-positive malignancy from both normal infection and non-viral cancer, providing new targets for diagnostic precision and therapeutic intervention.</p>","PeriodicalId":13568,"journal":{"name":"Infectious Agents and Cancer","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148194726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High-risk human papillomavirus positivity and associated factors among women living with HIV in public health facilities of Mekelle, Northern Ethiopia.","authors":"Mebrahtu Teweldemedhin Shfare, Hayelom Kahsay, Gebrecherkos Teame Gebrehiwot, Getachew Kahsu Abay, Tekle Amare Abrha, Dangew Weldegiorgis Araya, Girmay Alemseged Kahsay, Fisseha Assefa Embaye, Gerezgiher Buruh Abera, Dawit Wolday, Araya Gebreyesus Wasihun, Mahmud Abdulkader Mahmud, Tsehaye Asmelash Dejene","doi":"10.1186/s13027-026-00769-0","DOIUrl":"10.1186/s13027-026-00769-0","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Worldwide, it is believed that high-risk human papillomavirus (hr-HPV) strains are the root cause of many types of cancers, including cervical cancer, anorectal cancers, vaginal cancers, and penile cancers, with an estimated 922, 728 females diagnosed with HPV-related cancer in 2022. Particularly, in sub-Saharan Africa, the majority of women (55.13%) were affected by hr-HPV, and human immunodeficiency virus (HIV)-positive women have had double-fold higher risk of hr-HPV infection. Evidence is scarce in the study area; therefore, the current study aimed to assess the prevalence of hr-HPV and associated factors among HIV-positive women in public health facilities of Mekelle, Tigray, northern Ethiopia.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A health facility-based cross-sectional study was conducted in five conveniently selected public health facilities of Mekelle, northern Ethiopia, from December 10, 2024, to July 10, 2025. The study included 390 consecutively recruited HIV-positive women, from whom questionnaire-based interviews were made, and provider-collected cervical brush specimens were processed using the Abbot cervi-collect kit in accordance with standard procedures. Following automated deoxyribonucleic acid (DNA) extraction using the Abbot m2000sp, the presence of 14 hr-HPV genotypes was detected using the m2000rt real-time polymerase chain reaction (RT-PCR) assay. Bivariate and multivariate logistic regression analyses were performed to assess the statistical association between the potential factors and hr-HPV status. Finally, statistical significance was declared at p &lt; 0.05, along with the corresponding 95% confidence interval.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Result: &lt;/strong&gt;The mean ± SD age of the respondents was 42 years (42.82 ± 9.55). The majority, 231/390 (59.2%) of the respondents, were of a normal weight, and with an overall mean Body Mass Index (BMI) of 21.77 ± 3.86 kg/m&lt;sup&gt;2&lt;/sup&gt;. According to the RT-PCR, the overall prevalence of hr-HPV DNA positivity was 39.7% (155/390); [95% CI: 34.9-44.9%]. Specifically, the prevalence of HPV-16, HPV-18, and collectively the other hr-HPV types was 10.8% [95% CI: 7.7-13.8%], 3.6% [95% CI: 1.8-5.6%], and 32.7% [95% CI: 27.9-37.2%], respectively. In multivariable logistic regression analysis, condom use was assocatied with lower odds of hr-HPV infection [AOR = 0.23; 95%CI: 0.06-0.89; p = 0.034], whereas oral contraceptive use [AOR = 4.47; 95%CI: 1.39-14.28; p = 0.012], history of vaginal discharge [AOR = 2.61; 95%CI: 1.01-6.70; p = 0.046], genital ulcer disease [AOR = 4.09; 95%CI: 1.12-14.59; p = 0.030], history of unprotected sex before marriage [AOR = 2.20; 95%CI: 1.14-4.24; p = 0.017], lack of awareness about HPV-linked cervical cancer [AOR = 2.23; 95%CI: 1.18-4.24; p = 0.013], duration ( less than or equal to11 years) since ART initiation [AOR = 2.05; 95%CI: 1.13-3.74; p = 0.018], a history of 3 or more documented ART interruption events [AOR = 4.37; 95CI: 1.06-17.99; p = 0.041","PeriodicalId":13568,"journal":{"name":"Infectious Agents and Cancer","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13463756/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148101359","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":"Role of gut microbiota in cancer modulation: molecular mechanisms and emerging therapeutic strategies.","authors":"Subham Preetam, Jutishna Bora, Sthiti Porna Dutta, Nayan Talukdar, Sarvesh Rustagi, Shailendra Thapliyal, Sumira Malik, Neeraj Choudhary, Dinesh Kumar, Suresh Babu Kondaveeti","doi":"10.1186/s13027-026-00767-2","DOIUrl":"10.1186/s13027-026-00767-2","url":null,"abstract":"<p><p>The gut microbiota exerts profound effects on host physiology, immunity, and disease susceptibility, with growing evidence implicating its role in cancer initiation, progression, and therapy response. Dysbiosis and microbial-derived metabolites contribute to oncogenesis by modulating epithelial signalling, immune regulation, and systemic inflammation. This review synthesises current knowledge on the crosstalk between the gut microbiome and cancer, spanning molecular mechanisms, site-specific malignancies, and treatment outcomes. We discuss how microbial pathways, including NF-κB, STAT3, Wnt/β-catenin, and inflammasome activation, shape tumour biology, and how microbiota profiles correlate with cancer risk and progression in colorectal, gastric, liver, breast, gynaecological, and pulmonary cancers. Furthermore, we highlight the microbiome's impact on responses to chemotherapy, radiotherapy, and immunotherapy. Finally, we evaluate therapeutic strategies targeting the microbiota, from conventional dietary and probiotic interventions to cutting-edge approaches such as faecal microbiota transplantation, engineered bacterial strains, and microbiome-based biomarkers. Understanding these complex interactions offers novel opportunities to integrate microbiome science into precision oncology.</p>","PeriodicalId":13568,"journal":{"name":"Infectious Agents and Cancer","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13397764/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148042210","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":"Molecular characterization of HPV integrations in high-risk HPV-positive women and development of a prognostic signature based on integration-associated genes for cervical cancer.","authors":"Qiongying Lyu, Jiahui Zhao, Yurou Chen, Jiaqiang Xiong, Hairong Wang, Juan Zhang, Lihan Wang, Xiaoyan He, Wei Zhang","doi":"10.1186/s13027-026-00766-3","DOIUrl":"10.1186/s13027-026-00766-3","url":null,"abstract":"<p><strong>Background: </strong>HPV integration into the human genome is a key molecular event in the progression of cervical cancer carcinogenesis.</p><p><strong>Methods: </strong>This study utilized samples from high-risk HPV-positive women to investigate HPV integration. Integration-associated genes were screened based on HPV-DNA integration sequencing data from our local clinical cohort, and their expression levels and prognostic value were independently validated and used for model construction in the TCGA-CESC RNA-seq dataset. Using this integration-associated prognostic risk model, cervical cancer (CC) patients from TCGA were stratified into high-risk and low-risk groups. Differences in enrichment of PI3K-AKT pathway genes and immunotherapy response were analyzed between the two groups, and functional analysis was performed on differentially expressed immune-related genes between the subgroups.</p><p><strong>Results: </strong>The HPV integration rate gradually increases with the progression of cervical disease. The most frequent integration-related genes were KLF5, LINC00392, BCL11B and TP63. A risk model based on eight HPV integration-associated genes was developed, which could classify CC samples into high-risk groups with significantly shorter overall survival times compared to low-risk groups (P < 0.001). ROC curve evaluation showed that the AUCs for the 3, 5, and 7-year survival rates were 0.77, 0.74, and 0.76, respectively. The significant differences in PI3K-AKT pathway gene enrichment and prediction of immune therapy response were found between two risk groups.</p><p><strong>Conclusion: </strong>A integration-associated prognostic risk model based on genes derived from HPV integration hotspots shows significant association with patient survival and is correlated with distinct tumor microenvironment features, including PI3K-AKT pathway activity and predicted immunotherapy response.</p>","PeriodicalId":13568,"journal":{"name":"Infectious Agents and Cancer","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13224627/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148042183","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":"HIV, HPV, and oral health in Tanzania: a scoping review.","authors":"Kalipa Gedion, Elizabeth R Blackwood, Judith Mwobobia, Innocent Semali, Mainen Julius Moshi, Sira Owibingire, Richard O Mwaiswelo, Yohana Mashalla, Guido Ferrari, John Bartlett, Nosayaba Osazuwa-Peters","doi":"10.1186/s13027-026-00760-9","DOIUrl":"10.1186/s13027-026-00760-9","url":null,"abstract":"<p><strong>Background: </strong>People living with HIV (PLHIV) are at an increased risk of oral manifestations, including those linked to human papillomavirus (HPV). In Tanzania, the prevalence and impact of oral HPV among PLHIV remain unknown. This scoping review aimed to map evidence and identify gaps at the intersection of HIV, HPV, and oral health.</p><p><strong>Methods: </strong>We conducted a scoping review of studies on oral health in relation to HIV or HPV. Studies involving HPV or oral health among PLHIV were included, while studies conducted outside Tanzania, lacked empirical data, or did not report relevant outcomes were excluded. Outcomes were prevalence of oral manifestations, HPV detection, HPV vaccination, and intervention effectiveness.</p><p><strong>Results: </strong>Forty-four studies were included. One assessed HPV and oral health; none evaluated HPV vaccination effects on oral outcomes. Prevalence of oral manifestations among PLHIV increased from 10% to 34% over two decades. Antiretroviral therapy reduced oropharyngeal candidiasis but showed no effect on head and neck cancers.</p><p><strong>Conclusions: </strong>Evidence on HPV-related oral lesions among PLHIV in Tanzania is scarce. Research is needed to define prevalence, risk factors, and barriers to care, which will inform policies to expand HPV vaccination, strengthen the oral workforce, and integrate oral health into HIV services.</p>","PeriodicalId":13568,"journal":{"name":"Infectious Agents and Cancer","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13397644/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148029841","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":"Absence of chlamydial infection in ocular adnexal MALT lymphoma based on next-generation sequencing.","authors":"Yoshihiro Yakushijin, Kazuhiro Horiba, Masanori Hashino, Shintaro Yamanaka, Shinji Hasebe, Shoichiro Yamamoto, Tomomi Fujii, Katsuto Takenaka, Masaki Yasukawa","doi":"10.1186/s13027-026-00765-4","DOIUrl":"10.1186/s13027-026-00765-4","url":null,"abstract":"<p><strong>Objectives: </strong>Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) arises in various extranodal sites and has been linked to chronic inflammation, often triggered by infectious agents. Ocular adnexal (OA) MALT lymphoma has been associated with Chlamydophila psittaci (C. psittaci) in some regions. This study aimed to investigate the involvement of pathogenic microorganisms, including C. psittaci, in OA-MALT lymphoma.</p><p><strong>Methods: </strong>DNA was extracted from 17 formalin-fixed, paraffin-embedded OA-MALT lymphoma samples. Next-generation sequencing was performed, and reads were analyzed with bioinformatic pipelines to detect non-human DNA, focusing on complete or partial genomes of known pathogenic microorganisms, including C. psittaci strain 6BC and other bacteria implicated in lymphomagenesis.</p><p><strong>Results: </strong>Most sequencing reads mapped to the human genome. No complete or partial genomes of C. psittaci 6BC or other non-human pathogenic microorganisms were detected above background levels, and no consistent enrichment of microbial sequences was observed.</p><p><strong>Discussion: </strong>These findings suggest that, unlike in some Western cohorts, infectious agents such as C. psittaci are unlikely to play a major etiologic role in Japanese OA-MALT lymphoma.</p><p><strong>Conclusion: </strong>Our analysis suggests that infectious agents, including C. psittaci, may be not associated with OA-MALT lymphoma in Japan.</p>","PeriodicalId":13568,"journal":{"name":"Infectious Agents and Cancer","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13317347/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147837494","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":"Genomic and transcriptomic differences between neuroendocrine neoplasms and carcinomas with human papillomavirus (HPV).","authors":"Morgann Madill, Udhayvir Grewal, Harris Krause, Andrew Elliott, Marya Wahidi, Janet S Rader, Deanna Teoh, Soo J Park, John Wallbillich, David J Benjamin, Arash Rezazadeh Kalebasty, Penelope Duerksen-Hughes, Robert Morris, Radhika Gogoi, Fadi Zaiem, Thomas J Herzog, Premal H Thaker, Dave Bryant, Matthew Oberley, Heloisa Soares, Joanne Xiu, Andrew Hinton, Deepti Jain, Britt K Erickson, Martina Bazzaro, Emil Lou, Rouba Ali Fehmi","doi":"10.1186/s13027-026-00761-8","DOIUrl":"10.1186/s13027-026-00761-8","url":null,"abstract":"<p><strong>Introduction: </strong>Human papillomavirus (HPV) is a well-established oncogenic virus implicated in the development of several epithelial cancers, most notably cervical, anogenital, and oropharyngeal carcinomas. In contrast, neuroendocrine neoplasms (NENs)-a heterogeneous group of malignancies arising from neuroendocrine cells across various organ systems-have not traditionally been linked to HPV infection. In this study, we performed extensive genomic and transcriptomic profiling to compare HPV-positive NENs to HPV-positive non-NENs across anatomical sites, aiming to uncover biologically and clinically actionable differences.</p><p><strong>Methods: </strong>HPV16- and HPV18-positive tumors were identified from 101,343 solid tumors profiled at Caris Life Sciences (Phoenix, AZ) with DNA and RNA sequencing. Prevalence of pathogenic mutations and copy number amplifications were calculated. Fisher's exact/χ² tests were applied appropriately with p-values adjusted for multiple comparisons (p < 0.05).</p><p><strong>Results: </strong>HPV positivity was most frequent in cervical carcinomas (70%, 1200/1716). Importantly, 6% (96/1620) of NENs from all tissues were positive for HPV16 or HPV18. Among HPV-positive NENs, 93% were high-grade compared to 54% observed in HPV-negative NENs (p < 0.001), highlighting a strong association between HPV and tumor aggressiveness in this subset. Analysis of HPV-associated sites (cervix, anorectal region, and head and neck) revealed that HPV-positive NENs possess distinct genomic and transcriptomic landscapes compared to HPV-positive non-NENs. Notably, interferon signaling was significantly suppressed in HPV-positive NENs, suggesting a unique tumor-immune microenvironment.</p><p><strong>Conclusions: </strong>Our findings indicate that HPV-positive NENs form a distinct subset with unique genomic features, including reduced interferon signaling, compared to HPV-positive non-NENs. Thus, future studies focused on evaluating HPV status, along with genomic and transcriptomic characteristics, may uncover biologically and clinically actionable distinctions for this rare yet clinically significant tumor subgroup.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":13568,"journal":{"name":"Infectious Agents and Cancer","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13270718/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147814566","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":"Regulation of immune tolerance in hepatocellular carcinoma by liver diseases: a review.","authors":"Jinyi Li, Yuanda Liu","doi":"10.1186/s13027-026-00764-5","DOIUrl":"10.1186/s13027-026-00764-5","url":null,"abstract":"<p><p>The clinical benefit of immunotherapy for hepatocellular carcinoma (HCC) is often limited by innate immune tolerance. Traditional research focuses on the intrinsic escape mechanism of tumor cells or the generalized immunosuppression of the tumor microenvironment; however, it often ignores the chronic liver disease background of HCC patients with different etiologies. The aim of this review was to systematically discuss the mechanisms by which different underlying liver diseases, particularly metabolic dysfunction associated steatohepatitis, viral hepatitis (hepatitis B virus/hepatitis C virus) and alcoholic liver disease, specifically shape the liver immune microenvironment, thereby driving HCC to develop tolerance to immune checkpoint inhibitors. We further explored the molecular mechanisms by which various etiologies promote T cell exhaustion, expand immunosuppressive cells, and change the function of the gut-liver axis through unique pathways, such as metabolic dysfunction-associated steatohepatitis-related metabolic disorders and dysbiosis, sustained antigen stimulation and epigenetic regulation of viral hepatitis, and the hyperinflammatory chemokine network of alcoholic liver disease. In addition, this article systematically evaluates the potential synergistic or antagonistic effects of drugs used to treat these underlying liver diseases (e.g., lipid-lowering drugs, liver protective drugs, antiviral drugs, antifibrotic drugs, and new metabolic targeted drugs) on HCC immunotherapy. The objectives are to provide key mechanistic insights and strategic references for clinical combination drugs, as well as emphasize the corresponding individualized immunotherapy strategies for HCC caused by different diseases.</p>","PeriodicalId":13568,"journal":{"name":"Infectious Agents and Cancer","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13267724/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147770271","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":"Paired box 1 gene methylation as a promising triage strategy for atypical squamous cells: a retrospective comparison with high-risk HPV testing in cervical cancer screening.","authors":"Hong Tao, Zhengjiao Tong, Hongtao Li, Saiping Mao, Peng Gan, Xing Fan","doi":"10.1186/s13027-026-00763-6","DOIUrl":"10.1186/s13027-026-00763-6","url":null,"abstract":"<p><strong>Background: </strong>The triage of Atypical Squamous Cells (ASC) is pivotal in cervical cancer (CC) screening. This study aimed to evaluate the performance of paired box 1 gene methylation (PAX1^m) testing for triaging cervical intraepithelial neoplasia (CIN) grade 3 or worse (CIN3+) in an ASC population and to compare it with high-risk human papillomavirus (hrHPV) testing.</p><p><strong>Methods: </strong>This retrospective study was conducted from June 2023 to October 2025 and analyzed 1,305 women with ASC. Residual cervical cell samples were used for PAX1^m testing, and their hrHPV test results within two months were collected for comparison. All participants underwent colposcopy-biopsy to obtain the histopathological results. The area under the receiver operating characteristic curve (AUC), sensitivity, specificity of the two methods was calculated and compared. RESULTS PAX1M : difference of cross points (ΔCp) values showed a negative correlation with lesion severity (P _trend <0.001). For CIN3 + detection, PAX1^m (cut-off: ΔCp ≤ 11.74) demonstrated comparable sensitivity to hrHPV (94.6% vs. 94.6%), but with significantly higher specificity (66.0% vs. 10.4%, P < 0.001). Its AUC was also significantly higher to that of the hrHPV test. For CIN2 + detection, the AUC of PAX1^m (cut-off: ΔCp ≤ 11.74) was 0.716, which was significantly higher than that of the hrHPV test (0.544, P < 0.001). Furthermore, PAX1^m detected all cases of CC.</p><p><strong>Conclusion: </strong>In the triage of ASC, PAX1^m significantly improved the specificity for detecting CIN3 + while maintaining high sensitivity. These findings suggest that PAX1^m is a promising triage strategy with diagnostic performance superior to that of hrHPV, warranting further prospective validation of its clinical impact and cost-effectiveness.</p>","PeriodicalId":13568,"journal":{"name":"Infectious Agents and Cancer","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13244602/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147770341","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}