Tumour Virus Research最新文献

{"title":"HPV18E6 and CDK5 virus-host interaction is a prospective therapeutic target for HPV-positive cervical cancer","authors":"Chuanyun Xiao ,&nbsp;Lixin Wang ,&nbsp;Chichao Xia ,&nbsp;Paul Kay Sheung Chan ,&nbsp;Siaw Shi Boon","doi":"10.1016/j.tvr.2026.200339","DOIUrl":"10.1016/j.tvr.2026.200339","url":null,"abstract":"<div><div>The E6 oncoprotein encoded by the cancer-causing human papillomavirus (HPV) is vital for maintaining the ability of the virus to promote cell proliferation and cancer progression. This study identified that cyclin-dependent kinase 5 (CDK5) is a previously unidentified host target of E6 encoded by cancer-causing HPV genotypes. Although E6 may not be a phosphorylation substrate of CDK5, interaction with CDK5 nonetheless increases the steady-state level of E6. To further elucidate the significance of CDK5-E6 interaction, we adopted pharmacological inhibition and silencing approaches. Leveraging the computer-aided molecular docking and <em>in vitro</em> screening approaches, we identified CP681301, a potent CDK5 inhibitor, which can inhibit CDK5-E6 complex formation. More intriguingly, this study underlines that CP681301 can inhibit the E6-E6AP-p53 axis, conferring inhibition on cancer phenotypes of HPV-positive cancer cells, including the ability of cells to proliferate, transform, migrate and invade through Matrigel. Our study highlights that CDK5-E6 is a promising drug target for the design of next-generation targeted therapeutics for HPV-associated diseases.</div></div>","PeriodicalId":52381,"journal":{"name":"Tumour Virus Research","volume":"21 ","pages":"Article 200339"},"PeriodicalIF":8.1,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146138012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ad-VT oncolytic adenovirus suppresses bladder cancer via cAMP-dependent AMPK-Raptor activation and G2/M arrest","authors":"Dapeng Li ,&nbsp;Jing Lu ,&nbsp;Ran Zhu ,&nbsp;Xianyan Sun ,&nbsp;Cuiling Zhang ,&nbsp;Mingzhe Sun ,&nbsp;Chengyuan Ma ,&nbsp;Chao Shang ,&nbsp;Xiao Li","doi":"10.1016/j.tvr.2026.200337","DOIUrl":"10.1016/j.tvr.2026.200337","url":null,"abstract":"<div><div>Bladder cancer remains a leading cause of cancer-related mortality with limited therapeutic options. This study investigates the antitumor efficacy and mechanism of Ad-VT, a dual-specific oncolytic adenovirus expressing apoptin under the hTERT promoter, in bladder cancer. <em>In vitro</em>, Ad-VT selectively killed bladder cancer cells (UM-UC-3, T24, 5637, RT4) while sparing normal urothelial cells (SV-HUC-1), showing dose-dependent cytotoxicity (70 % inhibition at 100 MOI in 5637 cells). It induced G2/M phase arrest via downregulation of cyclin B1/cdc2 and upregulation of p-cdc2/p21. Mechanistically, Ad-VT elevated cAMP levels, activating the AMPK-Raptor-mTOR pathway. This was confirmed by pathway inhibitors (Dorsomorphin, ESI-09) and siRNA knockdown, which reversed cell cycle arrest and reduced cytotoxicity. <em>In vivo</em>, intratumoral Ad-VT injection suppressed UM-UC-3 xenograft growth, enhanced survival, and increased apoptosis while reducing proliferation. Crucially, AMPK inhibition attenuated Ad-VT's antitumor effects. These results demonstrate that Ad-VT exerts potent, tumor-selective activity against bladder cancer by inducing cAMP-dependent AMPK-Raptor-mTOR signaling and G2/M arrest, supporting its therapeutic potential.</div></div>","PeriodicalId":52381,"journal":{"name":"Tumour Virus Research","volume":"21 ","pages":"Article 200337"},"PeriodicalIF":8.1,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146097560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human cytomegalovirus UL82 promotes colorectal cancer cell proliferation through inhibiting the ubiquitination of OGDH via ANGPT2","authors":"Lanni Wang ,&nbsp;Ruini Li ,&nbsp;Haitao Ren ,&nbsp;Chaoyi Jiang ,&nbsp;Ye Shi ,&nbsp;Bing Wang ,&nbsp;Wenyu Jin ,&nbsp;Jiaxue Wang ,&nbsp;Linhua Lan ,&nbsp;Feng Xu ,&nbsp;Guangxin Xiang ,&nbsp;Xiaoqun Zheng","doi":"10.1016/j.tvr.2025.200322","DOIUrl":"10.1016/j.tvr.2025.200322","url":null,"abstract":"<div><div>Human cytomegalovirus (HCMV) infection and its association with tumorigenesis and tumor progression have garnered increasing attention. Previous research results have indicated that the detection rate of HCMV <em>UL82</em> is higher in colorectal cancer (CRC) tissues and is correlated with poor prognosis in patients, yet the underlying mechanisms remain unclear. In this study, a cell model transfected with UL82 was established. Through <em>in vitro</em> and <em>in vivo</em> experiments, it was found that UL82 promoted the proliferation of CRC cells. Transcriptomic and metabolomic analyses revealed that UL82 could influence CRC glucose metabolism and cell proliferation by upregulating the key TCA cycle enzyme OGDH. Additionally, UL82 also affected CRC cell proliferation by upregulating the expression of ANGPT2, and silencing ANGPT2 resulted in a reduction in OGDH protein levels. Finally, through the investigation of the ubiquitin-mediated degradation pathway of OGDH, it was demonstrated that ANGPT2 inhibited the protein degradation of OGDH via deubiquitination, thereby maintaining its stability. In summary, UL82 promotes CRC cell proliferation by upregulating ANGPT2, which inhibits the ubiquitin-mediated degradation of OGDH, suggesting that targeting the UL82/ANGPT2/OGDH axis may offer a potential clinical strategy for the diagnosis of CRC.</div></div>","PeriodicalId":52381,"journal":{"name":"Tumour Virus Research","volume":"20 ","pages":"Article 200322"},"PeriodicalIF":4.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144470582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"No evidence for restriction of Beta-HPV8 gene expression by epidermodysplasia verruciformis susceptibility genes CIB1, TMC6, or TMC8 in keratinocytes","authors":"Tina M. Rehm,&nbsp;Christina Parpoulas,&nbsp;Elke Straub,&nbsp;Thomas Iftner,&nbsp;Frank Stubenrauch","doi":"10.1016/j.tvr.2025.200328","DOIUrl":"10.1016/j.tvr.2025.200328","url":null,"abstract":"<div><div><em>Epidermodysplasia verruciformis</em> (EV) is an autosomal recessive disorder characterized by an extraordinary susceptibility to infections with human papillomaviruses (HPV), mainly from the genus beta. EV patients carry biallelic loss-of-function mutations in <em>TMC6</em> encoding Transmembrane channel-like protein 6 or EV protein 1 (EVER1), <em>TMC8</em> encoding Transmembrane channel-like protein 8 or EV protein 2 (EVER2), or <em>CIB1</em> encoding Calcium and integrin-binding protein 1. TMC6, TMC8 and CIB1 form a protein complex in the endoplasmic reticulum which has been hypothesized to act as a restriction factor for beta-HPV in keratinocytes. SiRNA-mediated knock-down of CIB1, TMC6, or TMC8 greatly reduces transcript and protein levels, but does not activate beta-HPV8 gene expression in normal keratinocytes. <em>TMC6</em> and <em>TMC8</em> transcript levels are much lower in normal and HPV-positive human keratinocytes than in CD4⁺ T-cells suggesting that the levels are too low for anti-viral activity. However, neither the activation of DNA sensing pathways by HPV genomes, supernatants from activated immune cells, nor activation of pathways important for the viral life cycle such as the DNA damage response or keratinocyte differentiation induce high levels of TMC6 or TMC8 in normal keratinocytes. This is consistent with findings that TMC6 and TMC8 do not restrict Mus musculus PV1 expression in keratinocytes. Taken together, we find no evidence for restriction factor activity of EV susceptibility genes for beta-HPV8 or conditions to induce high levels of TMC6 and TMC8 in keratinocytes. Thus, it is plausible that the EV phenotype in humans may be associated with an immune deficiency involving immune cells.</div></div>","PeriodicalId":52381,"journal":{"name":"Tumour Virus Research","volume":"20 ","pages":"Article 200328"},"PeriodicalIF":8.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145369359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Actinic Keratosis and Human Papillomaviruses: may their relationship constitute a new approach for actinic keratosis management?","authors":"Maria Antonia De Francesco ,&nbsp;Martina Salvi ,&nbsp;Roberta Gerami ,&nbsp;Maria Alberti ,&nbsp;Federico Cesanelli ,&nbsp;Irene Scarvaglieri ,&nbsp;Giorgio Tiecco ,&nbsp;Eugenia Quiros-Roldan","doi":"10.1016/j.tvr.2025.200330","DOIUrl":"10.1016/j.tvr.2025.200330","url":null,"abstract":"<div><div>Actinic keratosis (AK) is a precancerous lesion that typically develops on photo-damaged skin, particularly in older adults and immunocompromised individuals. Due to its high prevalence and its potential to progress to cancer, AK has become an important focus of research in recent years. If left untreated, AK can evolve into squamous cell carcinoma (SCC), a type of non-melanoma skin cancer (NMSC) that carries metastatic potential.</div><div>AK is driven by multiple pathogenic mechanisms such as inflammation induced by UV radiation, oxidative stress, inhibition of apoptosis and dysregulation of the cell cycle leading to an immunosuppressive condition. In recent years, human papillomaviruses (HPVs) have also been identified as potential cofactors along with chronic sun exposure.</div><div>This article reviews the current scientific evidence on the link between HPV skin infection and AK development, with a particular focus on the potential role of HPV vaccination in managing this condition.</div></div>","PeriodicalId":52381,"journal":{"name":"Tumour Virus Research","volume":"20 ","pages":"Article 200330"},"PeriodicalIF":8.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145490434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recurrent integration of domestic cat hepatitis B virus DNA near feline CCNE1 supports an oncogenic role in hepatocellular carcinoma in cats","authors":"João P. Cavasin ,&nbsp;Min-Chun Chen ,&nbsp;Harout Ajoyan ,&nbsp;Melanie J. Dobromylskyj ,&nbsp;Wei-Hsiang Huang ,&nbsp;Mason Jager ,&nbsp;Kate Van Brussel ,&nbsp;Rebecca Rockett ,&nbsp;Omid Nekouei ,&nbsp;Penny Watson ,&nbsp;Jason Bestwick ,&nbsp;Yan Ru Choi ,&nbsp;Jonathan A. Lidbury ,&nbsp;John M. Cullen ,&nbsp;Edward Holmes ,&nbsp;Jörg M. Steiner ,&nbsp;Thomas Tu ,&nbsp;Julia A. Beatty","doi":"10.1016/j.tvr.2025.200324","DOIUrl":"10.1016/j.tvr.2025.200324","url":null,"abstract":"<div><div>Hepatitis B virus (HBV) is the major cause of hepatocellular carcinoma (HCC) in humans. Domestic cat hepatitis B virus (DCHBV) naturally infects cats worldwide, but the oncogenic potential of this hepadnavirus is unclear. We investigated whether DCHBV contributes to feline HCC. Feline liver biopsies diagnosed with HCC (cases) and lymphocytic cholangitis (controls) were tested for DCHBV DNA by PCR. DCHBV-positive HCCs were further characterised by <em>in situ</em> hybridisation (ISH), whole-genome sequencing (WGS) and phylogenetic analysis. Targeted capture sequencing was used to identify and map viral DNA integrations. DCHBV DNA was detected in 17/71 (23.9 %) HCCs versus 0/88 controls (P &lt; 0.001). ISH confirmed hepatocyte-specific viral localization. Phylogenetic analysis placed six viruses in genotype A, and a seventh divergent virus in genotype B virus. Virus-host chimeric sequences, consistent with integration sites, were identified in 11/16 PCR-positive HCCs. Eight of the 11 integration sites were independently confirmed with WGS. Viral termini in integrated DCHBV sequences corresponded to double-stranded linear DNA, the substrate for HBV integration. Five unique DCHBV integrations fell within, or were adjacent to, the promoter of the feline homologue of proto-oncogene <em>CCNE1</em>, a recurrent target for HBV integration in human HCC. Our findings reveal a compelling association between DCHBV detection and HCC in cats. Critically, virus integration in DCHBV-associated HCC is described for the first time, supporting that, like HBV, DCHBV can promote hepatocarcinogenesis by insertional mutagenesis. Clarification of fundamental DCHBV virology <em>in vitro,</em> and the consequences of natural infection could advance disease-prevention strategies for feline and human patients.</div></div>","PeriodicalId":52381,"journal":{"name":"Tumour Virus Research","volume":"20 ","pages":"Article 200324"},"PeriodicalIF":8.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144668998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hepatitis B viral DNA integration occurs within three days of infection and is enhanced by ATR inhibition","authors":"Dong Li ,&nbsp;Jochen M. Wettengel ,&nbsp;Harout Ajoyan ,&nbsp;Vikki Ho ,&nbsp;Gabriela Wu ,&nbsp;Sarah Bae ,&nbsp;Henrik Zhang ,&nbsp;Delgerbat Boldbaatar ,&nbsp;Jacob George ,&nbsp;Mark W. Douglas ,&nbsp;Thomas Tu","doi":"10.1016/j.tvr.2025.200332","DOIUrl":"10.1016/j.tvr.2025.200332","url":null,"abstract":"<div><div>Chronic hepatitis B virus (HBV) infection is a major risk factor for hepatocellular carcinoma, with viral DNA integration into the host genome playing a pivotal role in oncogenesis. While HBV integration has been historically considered an event occurring late in a chronic infection, sensitive assays have detected integrations early infection. This study investigates the specific timing and molecular mechanisms of HBV DNA integration using a replication deficient HBV reporter system (HBV-Zeo) in HepG2-NTCP cells. Infection of this virus followed by positive selection led to cellular colony formation, showing that the input virus is the substrate that undergoes integration. By inducing DNA double-strand breaks via X-ray irradiation at specific timepoints after HBV infection, we observed a 2-3-fold increase in integration frequency when cells are irradiated between 16 and 76 h post-infection. Pharmacological inhibition of DNA repair pathways in this specific time window revealed that suppression of homologous recombination (HR) via ATR inhibitors significantly enhances integration rates (2.4–2.8-fold), while microhomology-mediated end joining (MMEJ) inhibition reduced integration to 17 % of untreated controls. These findings suggest that MMEJ plays a key role in HBV DNA integration occurring within hours of HBV infection. Together, our results advance understanding of HBV-associated hepatocarcinogenesis and may inform therapeutic strategies to disrupt viral integration and mitigate HBV-associated liver cancer risk.</div></div>","PeriodicalId":52381,"journal":{"name":"Tumour Virus Research","volume":"20 ","pages":"Article 200332"},"PeriodicalIF":8.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145650035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"JC polyomavirus neuroinvasion across the blood-brain barrier: Current understanding and emerging perspectives","authors":"Avraham S. Lukacher ,&nbsp;Wenqing Yuan ,&nbsp;Bethany A. O'Hara ,&nbsp;Kaitlin Garabian ,&nbsp;Sheila A. Haley ,&nbsp;Walter J. Atwood","doi":"10.1016/j.tvr.2025.200331","DOIUrl":"10.1016/j.tvr.2025.200331","url":null,"abstract":"<div><div>JC Polyomavirus (JCPyV) is the causative agent of progressive multifocal leukoencephalopathy (PML), an often-fatal demyelinating disease. Unfortunately, a diagnosis of PML occurs only after patients have suffered irreversible neuropathologies. One requirement for the development of PML is for JCPyV to enter the brain, but the mechanisms responsible for neuroinvasion have not been well established. The blood-brain barrier (BBB) is a potential site for JCPyV neuroinvasion. JCPyV DNA is found in the vascular endothelium in postmortem brain tissue from PML patients, and demyelinating lesions commonly emerge around vascularized sites. This review explores three potential pathways that may underlie JCPyV traversal across the BBB: diapedesis (“Trojan Horse”) via JCPyV-associated B cells, paracellular passage, and transcytosis. Elucidating the route and mechanism of JCPyV neuroinvasion will deepen our understanding of how the virus enters the brain before the manifestation of PML neuropathologies. Additionally, we discuss current limitations of <em>in vitro</em> BBB modeling and propose future approaches to more accurately capture the physiological dynamics underlying JCPyV neuroinvasion.</div></div>","PeriodicalId":52381,"journal":{"name":"Tumour Virus Research","volume":"20 ","pages":"Article 200331"},"PeriodicalIF":8.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145566198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The immunological heterogeneity of squamous cell carcinoma and adenocarcinoma of the uterine cervix: a systematic review","authors":"Marije Adriana Strikwerda ,&nbsp;Sabrina Anouck Weerstand ,&nbsp;George Louis Burchell ,&nbsp;Jacqueline Maria Tromp ,&nbsp;Constantijne Helene Mom ,&nbsp;Tanja Denise de Gruijl","doi":"10.1016/j.tvr.2025.200323","DOIUrl":"10.1016/j.tvr.2025.200323","url":null,"abstract":"<div><h3>Background</h3><div>Cervical cancer is the fourth most common malignancy in women worldwide and generally driven by persistent infection with high-risk human papillomavirus. Squamous cell carcinoma (SCC) and adenocarcinoma (AC) are the two most common histological subtypes, with a relative increase in adenocarcinomas in the last decades. The immunological differences between cervical squamous cell carcinoma and adenocarcinoma remain largely unexplored. Understanding these distinctions is crucial for developing tailored therapies that can improve treatment outcomes for patients with cervical cancer. This systematic review provides an overview of the immunological features of squamous cell carcinoma and adenocarcinoma of the uterine cervix.</div></div><div><h3>Methods</h3><div>A systematic search was performed in PubMed, Embase.com, Web of Science, and Cochrane Library. All articles addressing immunological features of squamous cell carcinoma and adenocarcinoma of the uterine cervix were reviewed and included based on predefined inclusion and exclusion criteria.</div></div><div><h3>Results</h3><div>In total, 3207 articles were screened, of which 43 were included. Studies show that cervical squamous cell carcinomas are characterised by a more inflamed tumour microenvironment, but also contain more regulatory T cells and immune checkpoints. In contrast, adenocarcinomas are characterised by lower immune cell infiltration, contributing to its poorer prognosis and more limited response to treatment.</div></div><div><h3>Conclusion</h3><div>The observed differences emphasize the need for further research into subtype-specific differences and distinct therapeutic strategies. For squamous cell carcinomas, future research should focus on combinatorial immune checkpoint blockade, including regulatory T cell-depleting strategies. For adenocarcinomas, oncolytic virotherapy, therapeutic vaccination, and oncogenic signalling interference should be explored.</div></div>","PeriodicalId":52381,"journal":{"name":"Tumour Virus Research","volume":"20 ","pages":"Article 200323"},"PeriodicalIF":4.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144596442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptomic profile of the immune genes, oncogenes, and tumor suppressor genes in HPV associated Cervical Intraepithelial Neoplasia 3 (CIN 3) and Cervical Squamous Cell Carcinoma (CSCC): Comparable expressions indicative of invasive potential.","authors":"Maaweya Awadalla, Halah Z Al Rawi, Reham M Alahmadi, Osamah T Khojah, Samia T Al-Shouli, Mansour I Almansour, Bandar Alosaimi","doi":"10.1016/j.tvr.2025.200327","DOIUrl":"10.1016/j.tvr.2025.200327","url":null,"abstract":"<p><p>Cervical cancer is the fourth most common cancer among women globally, with a woman dying every 2 min. Despite the need to understand the tumor microenvironment (TME) transcriptome of cervical squamous cell carcinoma (CSCC) and cervical intraepithelial neoplasia grade 3 (CIN 3), studies remain limited. This study compares the TME transcriptome of HPV-positive CSCC and CIN 3, analyzing 168 genes involved in tumor cell interactions with inflammatory and immune mediators, transcription, signal transduction, oncogenesis, tumor suppression, angiogenesis, and apoptosis. Co-expressed genes identified in HPV + CSCC and CIN 3 were analyzed using computational biology. Gene Ontology and KEGG enrichment identified relevant biological pathways and cancer hallmarks. Fifty-five co-expressed genes were linked to cancer pathways, inflammatory responses, cell migration, and development. KEGG enrichment highlighted viral protein interactions involving cytokines, IL-17 signaling, and chemokine receptor interactions. These genes were associated with cancer hallmark pathways, including angiogenesis, inflammation, proliferation, genomic instability, invasion, and metastasis. Their similar expression in CSCC and CIN 3 suggests a potential prognostic value and that CIN 3 progression may involve changes in gene expression. We propose the term \"CSCC-like carcinoma,\" indicating CIN 3's increased invasive potential at the molecular level.</p>","PeriodicalId":52381,"journal":{"name":"Tumour Virus Research","volume":" ","pages":"200327"},"PeriodicalIF":8.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12354963/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144769304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}