Pub Date : 2025-01-02DOI: 10.1016/j.tvr.2024.200312
Andrea Bilger, Paul F. Lambert
Human cancers are generally thought to develop over the course of decades. Such slow progression is well documented for a variety of cancers that we designate “slow-onset” cancers. “Rapid-onset” cancers, in contrast, can develop in a matter of months in humans or in as little as 9 days in mice. These cancers often develop under conditions that might be expected to accelerate cancer development: early development, immune deficiency, or viral infection. We will discuss rapid-onset cancers in the context of the "hallmarks of cancer" – properties cells must acquire in order to become malignant – focusing on how viruses are particularly well suited to causing rapid-onset cancer.
{"title":"Rapid-onset cancer","authors":"Andrea Bilger, Paul F. Lambert","doi":"10.1016/j.tvr.2024.200312","DOIUrl":"10.1016/j.tvr.2024.200312","url":null,"abstract":"<div><div>Human cancers are generally thought to develop over the course of decades. Such slow progression is well documented for a variety of cancers that we designate “slow-onset” cancers. “Rapid-onset” cancers, in contrast, can develop in a matter of months in humans or in as little as 9 days in mice. These cancers often develop under conditions that might be expected to accelerate cancer development: early development, immune deficiency, or viral infection. We will discuss rapid-onset cancers in the context of the \"hallmarks of cancer\" – properties cells must acquire in order to become malignant – focusing on how viruses are particularly well suited to causing rapid-onset cancer.</div></div>","PeriodicalId":52381,"journal":{"name":"Tumour Virus Research","volume":"19 ","pages":"Article 200312"},"PeriodicalIF":4.7,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11764593/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142928581","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}
Pub Date : 2024-12-27DOI: 10.1016/j.tvr.2024.200311
Weimer Kathleen
Infection by Human Papillomaviruses accounts for the most widespread sexually transmitted infection worldwide. Clinical presentation of these infections can range from subclinical and asymptomatic to anogenital cancers, with the latter associated with persistent infection over a significant period of time. Of the over 200 isotypes of the human virus identified, a subset of these has been characterized as high-risk due to their ability to induce oncogenesis. At the core of Papillomavirus pathogenesis sits three virally encoded oncoproteins: E5, E6, and E7. In this review we will discuss the respective roles of these proteins and how they contribute to carcinogenesis, evaluating key distinguishing features that separate them from their low-risk counterparts. Furthermore, we will consider the complex relationship between this trio and how their interwoven functional networks underpin the development of cancer.
{"title":"Too many cooks in the kitchen: HPV driven carcinogenesis – The result of collaboration or competition?","authors":"Weimer Kathleen","doi":"10.1016/j.tvr.2024.200311","DOIUrl":"10.1016/j.tvr.2024.200311","url":null,"abstract":"<div><div>Infection by Human Papillomaviruses accounts for the most widespread sexually transmitted infection worldwide. Clinical presentation of these infections can range from subclinical and asymptomatic to anogenital cancers, with the latter associated with persistent infection over a significant period of time. Of the over 200 isotypes of the human virus identified, a subset of these has been characterized as high-risk due to their ability to induce oncogenesis. At the core of Papillomavirus pathogenesis sits three virally encoded oncoproteins: E5, E6, and E7. In this review we will discuss the respective roles of these proteins and how they contribute to carcinogenesis, evaluating key distinguishing features that separate them from their low-risk counterparts. Furthermore, we will consider the complex relationship between this trio and how their interwoven functional networks underpin the development of cancer.</div></div>","PeriodicalId":52381,"journal":{"name":"Tumour Virus Research","volume":"19 ","pages":"Article 200311"},"PeriodicalIF":4.7,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11753912/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142904032","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}
Pub Date : 2024-12-20DOI: 10.1016/j.tvr.2024.200310
Lawrence Banks, Peter Stern
{"title":"Editorial: Tumour Virus Research on Virus Host Interactions and Cell Transformation.","authors":"Lawrence Banks, Peter Stern","doi":"10.1016/j.tvr.2024.200310","DOIUrl":"10.1016/j.tvr.2024.200310","url":null,"abstract":"","PeriodicalId":52381,"journal":{"name":"Tumour Virus Research","volume":" ","pages":"200310"},"PeriodicalIF":4.7,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142878659","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}
Pub Date : 2024-12-19DOI: 10.1016/j.tvr.2024.200309
Carly A. Burmeister, Saif F. Khan, Sharon Prince
Cervical cancer is primarily driven by persistent infection with high-risk human papillomavirus (HPV) strains and remains a significant global health challenge, particularly in low- and middle-income countries where late-stage diagnoses is common. While vaccination and screening programs have reduced incidence rates, the need for novel and more effacacious and cost-effective therapeutic options is therefore critical especially for advanced cervical cancer. This review highlights several key advances in the understanding of HPV-induced carcinogenesis and the development of therapeutic strategies over the past five years. Important areas of focus include the role of HPV oncoproteins E5, E6 and E7 in modulating signalling pathways, treatment strategies for precancerous lesions, the potential of natural compounds to target cervical cancer cells, and the emergence of immunotherapies, checkpoint inhibitors, antibody-drug conjugates, and novel drug combinations to treat cervical cancer. Additionally, lifestyle recommendations and the integration of natural supplements are discussed for their potential to enhance treatment efficacy and improve patient outcomes. The developments reported in this review underscore the evolving landscape of cervical cancer treatment and the need for continued research to validate and integrate these emerging therapies into clinical practice.
{"title":"Drugs and drug targets for the treatment of HPV-positive cervical cancer","authors":"Carly A. Burmeister, Saif F. Khan, Sharon Prince","doi":"10.1016/j.tvr.2024.200309","DOIUrl":"10.1016/j.tvr.2024.200309","url":null,"abstract":"<div><div>Cervical cancer is primarily driven by persistent infection with high-risk human papillomavirus (HPV) strains and remains a significant global health challenge, particularly in low- and middle-income countries where late-stage diagnoses is common. While vaccination and screening programs have reduced incidence rates, the need for novel and more effacacious and cost-effective therapeutic options is therefore critical especially for advanced cervical cancer. This review highlights several key advances in the understanding of HPV-induced carcinogenesis and the development of therapeutic strategies over the past five years. Important areas of focus include the role of HPV oncoproteins E5, E6 and E7 in modulating signalling pathways, treatment strategies for precancerous lesions, the potential of natural compounds to target cervical cancer cells, and the emergence of immunotherapies, checkpoint inhibitors, antibody-drug conjugates, and novel drug combinations to treat cervical cancer. Additionally, lifestyle recommendations and the integration of natural supplements are discussed for their potential to enhance treatment efficacy and improve patient outcomes. The developments reported in this review underscore the evolving landscape of cervical cancer treatment and the need for continued research to validate and integrate these emerging therapies into clinical practice.</div></div>","PeriodicalId":52381,"journal":{"name":"Tumour Virus Research","volume":"19 ","pages":"Article 200309"},"PeriodicalIF":4.7,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11733058/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142873371","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}
Pub Date : 2024-12-16DOI: 10.1016/j.tvr.2024.200307
Sarah A. Brendle , Jingwei Li , Dongxiao Sun , Junjia Zhu , Angela N. Henderson-Redmond , Daniel J. Morgan , Karla K. Balogh , Danielle Covington , Debra A. Shearer , Jiafen Hu
We used our mouse papillomavirus (MmuPV1) model to test the hypothesis that two primary psychoactive ingredients of marijuana, Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), promote papillomavirus persistence in the oral mucosa of infected mice. We conducted intraperitoneal (ip) injections of a moderate dose (3 mg/kg) of either CBD and/or THC in both male and female athymic nude mice and followed the mice up to 20 weeks post-infection. These doses are comparable to what is estimated for human conventional cannabis consumption. All mice were infected with MmuPV1 in the oral cavity at week 4 post-ip delivery of CBD, THC, or a combination of THC and CBD (T + C). THC and CBD were detected in the blood of treated mice for up to 72 h after ip injection. Significantly higher levels of viral DNA were detected in males from both CBD and T + C-treated groups compared to those in the control group at 9- 10-and 12-weeks post infection. A marginally increased viral RNA was also detected in the infected tongues of males in all tested groups compared to that in males in the vehicle control group; the opposite was observed in females. We detected significantly higher levels of dermal dendritic cells (CD205+CD11c+), granulocytes (Ly6G+), but macrophages (F4-80+) recruited to the infected tongues of CBD-treated females. Our findings suggest that CBD may play a role in promoting MmuPV1 persistence in the oral cavity.
{"title":"Intraperitoneal delivery of cannabidiol (CBD) and Δ9-tetrahydocannabinol (THC) promotes papillomavirus infections in athymic nude mice","authors":"Sarah A. Brendle , Jingwei Li , Dongxiao Sun , Junjia Zhu , Angela N. Henderson-Redmond , Daniel J. Morgan , Karla K. Balogh , Danielle Covington , Debra A. Shearer , Jiafen Hu","doi":"10.1016/j.tvr.2024.200307","DOIUrl":"10.1016/j.tvr.2024.200307","url":null,"abstract":"<div><div>We used our mouse papillomavirus (MmuPV1) model to test the hypothesis that two primary psychoactive ingredients of marijuana, Δ<sup>9</sup>-tetrahydrocannabinol (THC) and cannabidiol (CBD), promote papillomavirus persistence in the oral mucosa of infected mice. We conducted intraperitoneal (ip) injections of a moderate dose (3 mg/kg) of either CBD and/or THC in both male and female athymic nude mice and followed the mice up to 20 weeks post-infection. These doses are comparable to what is estimated for human conventional cannabis consumption. All mice were infected with MmuPV1 in the oral cavity at week 4 post-ip delivery of CBD, THC, or a combination of THC and CBD (T + C). THC and CBD were detected in the blood of treated mice for up to 72 h after ip injection. Significantly higher levels of viral DNA were detected in males from both CBD and T + C-treated groups compared to those in the control group at 9- 10-and 12-weeks post infection. A marginally increased viral RNA was also detected in the infected tongues of males in all tested groups compared to that in males in the vehicle control group; the opposite was observed in females. We detected significantly higher levels of dermal dendritic cells (CD205<sup>+</sup>CD11c<sup>+</sup>), granulocytes (Ly6G<sup>+</sup>), but macrophages (F4-80+) recruited to the infected tongues of CBD-treated females. Our findings suggest that CBD may play a role in promoting MmuPV1 persistence in the oral cavity.</div></div>","PeriodicalId":52381,"journal":{"name":"Tumour Virus Research","volume":"19 ","pages":"Article 200307"},"PeriodicalIF":4.7,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11731512/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142856753","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}
Pub Date : 2024-12-16DOI: 10.1016/j.tvr.2024.200308
S. Dick , D.A.M. Heideman , J. Berkhof , R.D.M. Steenbergen , M.C.G. Bleeker
DNA methylation of host-cell genes is an epigenetic process that regulates gene expression and is associated with cervical cancer development. Studies on the natural history of cervical intraepithelial neoplasia (CIN) and the molecular alterations associated with cervical carcinogenesis led to the identification of several host-cell DNA methylation markers. Over the past years, various studies on methylation markers have shown promising results in terms of diagnostic and prognostic value to improve cervical cancer screening and management of CIN. This review provides an overview of the clinical indications of host-cell DNA methylation markers in cervical screening and management of CIN, and outlines avenues for further applications.
{"title":"Clinical indications for host-cell DNA methylation markers in cervical screening and management of cervical intraepithelial neoplasia: A review","authors":"S. Dick , D.A.M. Heideman , J. Berkhof , R.D.M. Steenbergen , M.C.G. Bleeker","doi":"10.1016/j.tvr.2024.200308","DOIUrl":"10.1016/j.tvr.2024.200308","url":null,"abstract":"<div><div>DNA methylation of host-cell genes is an epigenetic process that regulates gene expression and is associated with cervical cancer development. Studies on the natural history of cervical intraepithelial neoplasia (CIN) and the molecular alterations associated with cervical carcinogenesis led to the identification of several host-cell DNA methylation markers. Over the past years, various studies on methylation markers have shown promising results in terms of diagnostic and prognostic value to improve cervical cancer screening and management of CIN. This review provides an overview of the clinical indications of host-cell DNA methylation markers in cervical screening and management of CIN, and outlines avenues for further applications.</div></div>","PeriodicalId":52381,"journal":{"name":"Tumour Virus Research","volume":"19 ","pages":"Article 200308"},"PeriodicalIF":4.7,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11728911/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142856752","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}
Pub Date : 2024-12-15DOI: 10.1016/j.tvr.2024.200303
Amir Basis, Rakefet Sharf, Tamar Kleinberger
Viruses exploit several cellular pathways to support their replication, and many of these virus-targeted pathways are also important for cancer growth. Consequently, studying virus-host interactions offers valuable insights into tumorigenesis and can suggest the development of novel anti-cancer therapies, with oncolytic viruses being one well-known example. The adenovirus E4orf4 protein, which disrupts several host regulatory pathways to facilitate viral infection, also functions as a potent anti-cancer agent when expressed independently. E4orf4 can selectively kill a wide range of cancer cell lines while sparing non-cancerous cells. Moreover, it effectively eliminated cancer in an in vivo Drosophila model without causing significant harm to normal tissues. In this study we provide evidence that an E4orf4-mimicking drug cocktail, comprising sublethal doses of four FDA-approved drugs targeting the pathways disrupted by E4orf4, significantly enhanced cancer cell death in many cancer cell types compared with individual drugs or less inclusive drug combinations. The quadruple drug cocktail was not toxic in non-cancerous cells. These findings provide a proof-of-principle for the potential application of virus-host interaction studies to design an effective E4orf4-based cancer therapy. Further investigation of E4orf4 interactions with the host cell will likely improve this E4orf4-based therapy by adding drugs that disrupt additional pathways. Crucially, the E4orf4-based approach offers a strategic advantage by avoiding the time-consuming development of novel drugs. Instead, it leverages existing drugs, including those that might be too toxic for use as monotherapies, by employing them at sublethal concentrations in combination. Thus, it provides a feasible and efficient method for advancing cancer therapy.
{"title":"The adenoviral E4orf4 protein: A multifunctional protein serving as a guide for treating cancer, a multifactorial disease.","authors":"Amir Basis, Rakefet Sharf, Tamar Kleinberger","doi":"10.1016/j.tvr.2024.200303","DOIUrl":"10.1016/j.tvr.2024.200303","url":null,"abstract":"<p><p>Viruses exploit several cellular pathways to support their replication, and many of these virus-targeted pathways are also important for cancer growth. Consequently, studying virus-host interactions offers valuable insights into tumorigenesis and can suggest the development of novel anti-cancer therapies, with oncolytic viruses being one well-known example. The adenovirus E4orf4 protein, which disrupts several host regulatory pathways to facilitate viral infection, also functions as a potent anti-cancer agent when expressed independently. E4orf4 can selectively kill a wide range of cancer cell lines while sparing non-cancerous cells. Moreover, it effectively eliminated cancer in an in vivo Drosophila model without causing significant harm to normal tissues. In this study we provide evidence that an E4orf4-mimicking drug cocktail, comprising sublethal doses of four FDA-approved drugs targeting the pathways disrupted by E4orf4, significantly enhanced cancer cell death in many cancer cell types compared with individual drugs or less inclusive drug combinations. The quadruple drug cocktail was not toxic in non-cancerous cells. These findings provide a proof-of-principle for the potential application of virus-host interaction studies to design an effective E4orf4-based cancer therapy. Further investigation of E4orf4 interactions with the host cell will likely improve this E4orf4-based therapy by adding drugs that disrupt additional pathways. Crucially, the E4orf4-based approach offers a strategic advantage by avoiding the time-consuming development of novel drugs. Instead, it leverages existing drugs, including those that might be too toxic for use as monotherapies, by employing them at sublethal concentrations in combination. Thus, it provides a feasible and efficient method for advancing cancer therapy.</p>","PeriodicalId":52381,"journal":{"name":"Tumour Virus Research","volume":" ","pages":"200303"},"PeriodicalIF":4.7,"publicationDate":"2024-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142840250","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}
Pub Date : 2024-12-13DOI: 10.1016/j.tvr.2024.200306
Matthew R. Googins, Ping An, Christian H. Gauthier, James M. Pipas
All members of the polyomavirus family encode a large T antigen (LT) protein that plays essential roles in viral DNA replication, regulation of viral gene expression, and the manipulation of numerous cellular pathways. Over 100 polyomaviruses have been discovered in hosts ranging from arthropods and fish to mammals, including fourteen that infect humans. LT is among the most studied viral proteins with thousands of articles describing its functions in viral productive infection and tumorigenesis. However, nearly all knowledge of LT activities is based on the studies of simian virus 40 (SV40) and a few other viruses. Comparative studies of LT proteins of different polyomaviruses have revealed a remarkable diversity in the mechanisms by which LT proteins function across different polyomavirus species. This review focuses on human polyomaviruses highlights the similarities and differences between polyomavirus LTs and highlights gaps in our understanding of this protein family. The concentration of knowledge around SV40 LT and the corresponding lack of mechanistic studies on LT proteins encoded by other human and animal polyomaviruses severely constrains our understanding of the biology of this important virus family.
{"title":"Polyomavirus large T antigens: Unraveling a complex interactome","authors":"Matthew R. Googins, Ping An, Christian H. Gauthier, James M. Pipas","doi":"10.1016/j.tvr.2024.200306","DOIUrl":"10.1016/j.tvr.2024.200306","url":null,"abstract":"<div><div>All members of the polyomavirus family encode a large T antigen (LT) protein that plays essential roles in viral DNA replication, regulation of viral gene expression, and the manipulation of numerous cellular pathways. Over 100 polyomaviruses have been discovered in hosts ranging from arthropods and fish to mammals, including fourteen that infect humans. LT is among the most studied viral proteins with thousands of articles describing its functions in viral productive infection and tumorigenesis. However, nearly all knowledge of LT activities is based on the studies of simian virus 40 (SV40) and a few other viruses. Comparative studies of LT proteins of different polyomaviruses have revealed a remarkable diversity in the mechanisms by which LT proteins function across different polyomavirus species. This review focuses on human polyomaviruses highlights the similarities and differences between polyomavirus LTs and highlights gaps in our understanding of this protein family. The concentration of knowledge around SV40 LT and the corresponding lack of mechanistic studies on LT proteins encoded by other human and animal polyomaviruses severely constrains our understanding of the biology of this important virus family.</div></div>","PeriodicalId":52381,"journal":{"name":"Tumour Virus Research","volume":"19 ","pages":"Article 200306"},"PeriodicalIF":4.7,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11720896/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142830202","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}
Pub Date : 2024-12-12DOI: 10.1016/j.tvr.2024.200299
Emma Robinson , Isabel Rodriguez , Victor Argueta , Yi Xie , Hong Lou , Rose Milano , Hyo Jung Lee , Laurie Burdett , Sambit K. Mishra , Meredith Yeager , Lisa Mirabello , Michael Dean , Roberto Orozco
To better understand cervical cancer progression, we analyzed RNA from 262 biopsies from women referred for colposcopy. We determined the HPV type and analyzed the expression of 51 genes. HPV31 was significantly more prevalent in precancer than stage 1 cancer and invasive cancer (p < 0.0001), and HPV16 increased in invasive disease (p < 0.0001). CCNE1, MELTF, and ULBP2 were significantly increased in HPV16-positive compared to HPV31 precancers, while NECTIN2 and HLA-E expression decreased. Markers of the innate immune system, DNA repair genes, and cell cycle genes are significantly increased during cancer progression (p = 0.0001). In contrast, the TP53 and RB1 tumor suppressor gene expression is significantly decreased in cancer cells. The T cell markers CD28 and FLT3LG expression decreased in cancer while FOXP3, IDO1, and ULBP2 expression increased. There is a significantly higher survival rate in individuals with increased expression of CD28 (p = 0.0005), FOXP3 (p = 0.0002), IDO1 (p = 0.038), FLT3LG (p = 0.026), APOBEC3B (p = 0.0011), and RUNX3 (p = 0.019), and a significantly lower survival rate in individuals with increased expression of ULBP2 (p = 0.035). These results will help us elucidate the molecular factors influencing the progression of cervical precancer to cancer. Understanding the risk of progression of specific HPV types and sublineages may aid in the triage of positive patients, and better knowledge of the immune response may aid in developing and applying immunotherapies.
{"title":"Analysis of the progression of cervical cancer in a low-and-middle-income country: From pre-malignancy to invasive disease","authors":"Emma Robinson , Isabel Rodriguez , Victor Argueta , Yi Xie , Hong Lou , Rose Milano , Hyo Jung Lee , Laurie Burdett , Sambit K. Mishra , Meredith Yeager , Lisa Mirabello , Michael Dean , Roberto Orozco","doi":"10.1016/j.tvr.2024.200299","DOIUrl":"10.1016/j.tvr.2024.200299","url":null,"abstract":"<div><div>To better understand cervical cancer progression, we analyzed RNA from 262 biopsies from women referred for colposcopy. We determined the HPV type and analyzed the expression of 51 genes. HPV31 was significantly more prevalent in precancer than stage 1 cancer and invasive cancer (p < 0.0001), and HPV16 increased in invasive disease (p < 0.0001). <em>CCNE1</em>, <em>MELTF</em>, and <em>ULBP2</em> were significantly increased in HPV16-positive compared to HPV31 precancers, while <em>NECTIN2</em> and <em>HLA-E</em> expression decreased. Markers of the innate immune system, DNA repair genes, and cell cycle genes are significantly increased during cancer progression (p = 0.0001). In contrast, the <em>TP53</em> and <em>RB1</em> tumor suppressor gene expression is significantly decreased in cancer cells. The T cell markers <em>CD28</em> and <em>FLT3LG</em> expression decreased in cancer while <em>FOXP3, IDO1</em>, and <em>ULBP2</em> expression increased. There is a significantly higher survival rate in individuals with increased expression of <em>CD28</em> (p = 0.0005), <em>FOXP3</em> (p = 0.0002), <em>IDO1</em> (p = 0.038), <em>FLT3LG</em> (p = 0.026), <em>APOBEC3B</em> (p = 0.0011), and <em>RUNX3</em> (p = 0.019), and a significantly lower survival rate in individuals with increased expression of <em>ULBP2</em> (p = 0.035). These results will help us elucidate the molecular factors influencing the progression of cervical precancer to cancer. Understanding the risk of progression of specific HPV types and sublineages may aid in the triage of positive patients, and better knowledge of the immune response may aid in developing and applying immunotherapies.</div></div>","PeriodicalId":52381,"journal":{"name":"Tumour Virus Research","volume":"19 ","pages":"Article 200299"},"PeriodicalIF":4.7,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11729683/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142822834","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}
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