Pub Date : 2025-06-01Epub 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":"2025-06-01","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 : 2025-06-01Epub 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":"2025-06-01","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}
Pub Date : 2025-06-01Epub 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":"<div><div>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 <em>in vivo Drosophila</em> model without causing significant harm to normal tissues.</div><div>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.</div><div>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.</div></div>","PeriodicalId":52381,"journal":{"name":"Tumour Virus Research","volume":"19 ","pages":"Article 200303"},"PeriodicalIF":4.7,"publicationDate":"2025-06-01","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-01Epub Date: 2025-03-07DOI: 10.1016/j.tvr.2025.200315
Mariano A. Molina , Sneha Biswas , Omar Jiménez-Vázquez , Jason M. Bodily
Human papillomavirus (HPV) 16 infection initiates upon viral entry into the basal cells of the epithelium. The virus manipulates signaling pathways to complete its life cycle, which depends on cellular differentiation. The virus expresses the oncoproteins E5, E6, and E7 to promote immune evasion, cell cycle progression, apoptosis inhibition, and viral replication. The least studied viral oncoprotein is E5 (16E5), which can regulate epithelial growth factor receptor (GFR) signaling pathways. GFRs such as transforming growth factor-beta receptor (TGFBR), epidermal growth factor receptor (EGFR), and keratinocyte growth factor receptor (KGFR) have essential roles in cell growth, differentiation, and proliferation. These receptors obtain their ligands from the microenvironment, and once activated, regulate cellular behavior in the epithelium. GFRs therefore represent valuable targets for the virus to establish and maintain a cellular environment supportive of infection. The ability of 16E5 to regulate proliferation and differentiation varies through the differentiating epithelium, making it necessary to adequately describe the association between 16E5 and GFRs. Here we summarize the regulation of GFR signaling pathways by 16E5, discuss the roles of stromal growth factors, and outline unresolved questions over cellular differentiation and proliferation during the HPV life cycle.
{"title":"Regulation of epithelial growth factor receptors by the oncoprotein E5 during the HPV16 differentiation-dependent life cycle","authors":"Mariano A. Molina , Sneha Biswas , Omar Jiménez-Vázquez , Jason M. Bodily","doi":"10.1016/j.tvr.2025.200315","DOIUrl":"10.1016/j.tvr.2025.200315","url":null,"abstract":"<div><div>Human papillomavirus (HPV) 16 infection initiates upon viral entry into the basal cells of the epithelium. The virus manipulates signaling pathways to complete its life cycle, which depends on cellular differentiation. The virus expresses the oncoproteins E5, E6, and E7 to promote immune evasion, cell cycle progression, apoptosis inhibition, and viral replication. The least studied viral oncoprotein is E5 (16E5), which can regulate epithelial growth factor receptor (GFR) signaling pathways. GFRs such as transforming growth factor-beta receptor (TGFBR), epidermal growth factor receptor (EGFR), and keratinocyte growth factor receptor (KGFR) have essential roles in cell growth, differentiation, and proliferation. These receptors obtain their ligands from the microenvironment, and once activated, regulate cellular behavior in the epithelium. GFRs therefore represent valuable targets for the virus to establish and maintain a cellular environment supportive of infection. The ability of 16E5 to regulate proliferation and differentiation varies through the differentiating epithelium, making it necessary to adequately describe the association between 16E5 and GFRs. Here we summarize the regulation of GFR signaling pathways by 16E5, discuss the roles of stromal growth factors, and outline unresolved questions over cellular differentiation and proliferation during the HPV life cycle.</div></div>","PeriodicalId":52381,"journal":{"name":"Tumour Virus Research","volume":"19 ","pages":"Article 200315"},"PeriodicalIF":4.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143577986","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 : 2025-06-01Epub Date: 2025-03-20DOI: 10.1016/j.tvr.2025.200317
Julia Mai , Masih Nazari , Thomas Stamminger , Sabrina Schreiner
Daxx and HIRA are key proteins in the host response to DNA virus infections. Daxx is involved in apoptosis, transcription regulation, and stress responses. During DNA virus infections, Daxx helps modulate the immune response and viral progression. Viruses like adenoviruses and herpesviruses can exploit Daxx to evade immune detection, either by targeting it for degradation or inhibiting its function. Daxx also interacts with chromatin to regulate transcription, which viruses can manipulate to enhance their own gene expression and replication. HIRA is a histone chaperone and reported to be essential for chromatin assembly and gene regulation. It plays a critical role in maintaining chromatin structure and modulating gene accessibility. During DNA virus infection, HIRA influences chromatin remodeling, affecting both viral and host DNA accessibility, which impacts viral replication and gene expression. Additionally, the histone variant H3.3 is crucial for maintaining active chromatin states. It is incorporated into chromatin independently of DNA replication and is associated with active gene regions. During viral infections, H3.3 dynamics can be altered, affecting viral genome accessibility and replication efficiency. Overall, Daxx and HIRA are integral to orchestrating viral infection programs, maintaining latency and/or persistence, and influencing virus-induced transformation by modulating chromatin dynamics and host immune responses, making them significant targets for therapeutic strategies once fully understood. Here, we summarize various DNA viruses and their crosstalk with Daxx and HIRA.
{"title":"Daxx and HIRA go viral – How chromatin remodeling complexes affect DNA virus infection","authors":"Julia Mai , Masih Nazari , Thomas Stamminger , Sabrina Schreiner","doi":"10.1016/j.tvr.2025.200317","DOIUrl":"10.1016/j.tvr.2025.200317","url":null,"abstract":"<div><div>Daxx and HIRA are key proteins in the host response to DNA virus infections. Daxx is involved in apoptosis, transcription regulation, and stress responses. During DNA virus infections, Daxx helps modulate the immune response and viral progression. Viruses like adenoviruses and herpesviruses can exploit Daxx to evade immune detection, either by targeting it for degradation or inhibiting its function. Daxx also interacts with chromatin to regulate transcription, which viruses can manipulate to enhance their own gene expression and replication. HIRA is a histone chaperone and reported to be essential for chromatin assembly and gene regulation. It plays a critical role in maintaining chromatin structure and modulating gene accessibility. During DNA virus infection, HIRA influences chromatin remodeling, affecting both viral and host DNA accessibility, which impacts viral replication and gene expression. Additionally, the histone variant H3.3 is crucial for maintaining active chromatin states. It is incorporated into chromatin independently of DNA replication and is associated with active gene regions. During viral infections, H3.3 dynamics can be altered, affecting viral genome accessibility and replication efficiency. Overall, Daxx and HIRA are integral to orchestrating viral infection programs, maintaining latency and/or persistence, and influencing virus-induced transformation by modulating chromatin dynamics and host immune responses, making them significant targets for therapeutic strategies once fully understood. Here, we summarize various DNA viruses and their crosstalk with Daxx and HIRA.</div></div>","PeriodicalId":52381,"journal":{"name":"Tumour Virus Research","volume":"19 ","pages":"Article 200317"},"PeriodicalIF":4.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143694439","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 : 2025-06-01Epub 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":"2025-06-01","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}
Evaluating novel human papillomavirus (HPV) tests in well-designed, population-based screening studies is essential for ensuring the benefits of cervical cancer screening.
Methods
8638 women aged over 25 years from China underwent HPV screening using a PCR-based full genotyping HPV assay (SureX HPV), alongside hybrid-capture HPV tests (DH2/careHPV) and cytology. Any abnormal results triggered colposcopy and biopsy if indicated. Screening performance was evaluated for detecting cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and CIN3+.
Results
The high-risk HPV (hrHPV) positive rate by SureX HPV was significantly higher than by careHPV (11.0 % vs. 8.2 %, P <0.01) but similar to DH2 HPV (12.0 % vs. 11.5 %, P =0.34). The overall agreement rates between SureX HPV and careHPV/DH2 HPV were 93.5 % (Kappa=0.63) and 94.0 % (Kappa=0.71). For CIN2+ detection, SureX HPV showed not-significantly higher sensitivity than careHPV (91.2 % vs 82.5 %, P =0.18) but lower specificity (91.2 % vs. 93.1 %, P <0.01). Compared to DH2, SureX HPV demonstrated comparable sensitivity (95.7 % for both, P =1.0) and specificity (89.5 % vs. 90.2 %, P =0.21). Similar patterns were observed for CIN3+ detection. The area under the receiver operating characteristic curve (AUC) for the SureX HPV was similar to hybrid-capture HPV tests (P >0.05 for both) and significantly higher than the cytology (ASC-US+) test for CIN2+/CIN3+ detection (P <0.05 for both).
Conclusions
The PCR-based SureX HPV test demonstrated good concordance with well-validated hybrid-capture HPV tests in detecting hrHPV and CIN2+/CIN3+. Despite its slightly suboptimal specificity, SureX HPV could be an alternative in primary screening due to its full genotyping capability.
背景：在设计良好、基于人群的筛查研究中评估新型人乳头瘤病毒（HPV）检测对于确保宫颈癌筛查的益处至关重要。方法：来自中国的8638名年龄在25岁以上的女性使用基于pcr的全基因分型HPV检测（SureX HPV）、混合捕获HPV检测（DH2/careHPV）和细胞学进行HPV筛查。如果有任何异常结果，则需要进行阴道镜检查和活检。评估宫颈上皮内瘤变2级及以上（CIN2+）和CIN3+的筛查效果。结果：SureX HPV检测的高危HPV （hrHPV）阳性率显著高于careHPV (11.0% vs. 8.2%, P < 0.05)，且显著高于细胞学（ASC-US+）检测CIN2+/CIN3+的阳性率（P < 0.05）。结论：基于pcr的SureX HPV检测在检测hrHPV和CIN2+/CIN3+方面与经过验证的混合捕获HPV检测具有良好的一致性。尽管其特异性略低于最佳水平，但由于其完整的基因分型能力，SureX HPV可作为初级筛查的替代方法。
{"title":"Clinical performance of the SureX PCR HPV test versus hybrid capture assays (DH2/careHPV) in primary cervical cancer screening","authors":"Yumei Ouyang , Guzhanuer Abuduxikuer , Tangnuer Abulimiti , Guligeina Abudurexiti , Qian Zhuo , Wenyun Li , Kadeliya Muhetaer , Shaliya Abuduwufu , Gulixian Tuerxun , Remila Rezhake , Guzhalinuer Abulizi","doi":"10.1016/j.tvr.2025.200319","DOIUrl":"10.1016/j.tvr.2025.200319","url":null,"abstract":"<div><h3>Background</h3><div>Evaluating novel human papillomavirus (HPV) tests in well-designed, population-based screening studies is essential for ensuring the benefits of cervical cancer screening.</div></div><div><h3>Methods</h3><div>8638 women aged over 25 years from China underwent HPV screening using a PCR-based full genotyping HPV assay (SureX HPV), alongside hybrid-capture HPV tests (DH2/careHPV) and cytology. Any abnormal results triggered colposcopy and biopsy if indicated. Screening performance was evaluated for detecting cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and CIN3+.</div></div><div><h3>Results</h3><div>The high-risk HPV (hrHPV) positive rate by SureX HPV was significantly higher than by careHPV (11.0 % vs. 8.2 %, <em>P</em> <0.01) but similar to DH2 HPV (12.0 % vs. 11.5 %, <em>P</em> =0.34). The overall agreement rates between SureX HPV and careHPV/DH2 HPV were 93.5 % (Kappa=0.63) and 94.0 % (Kappa=0.71). For CIN2+ detection, SureX HPV showed not-significantly higher sensitivity than careHPV (91.2 % vs 82.5 %, <em>P</em> =0.18) but lower specificity (91.2 % vs. 93.1 %, <em>P</em> <0.01). Compared to DH2, SureX HPV demonstrated comparable sensitivity (95.7 % for both, <em>P</em> =1.0) and specificity (89.5 % vs. 90.2 %, <em>P</em> =0.21). Similar patterns were observed for CIN3+ detection. The area under the receiver operating characteristic curve (AUC) for the SureX HPV was similar to hybrid-capture HPV tests (<em>P</em> >0.05 for both) and significantly higher than the cytology (ASC-US+) test for CIN2+/CIN3+ detection (<em>P</em> <0.05 for both).</div></div><div><h3>Conclusions</h3><div>The PCR-based SureX HPV test demonstrated good concordance with well-validated hybrid-capture HPV tests in detecting hrHPV and CIN2+/CIN3+. Despite its slightly suboptimal specificity, SureX HPV could be an alternative in primary screening due to its full genotyping capability.</div></div>","PeriodicalId":52381,"journal":{"name":"Tumour Virus Research","volume":"19 ","pages":"Article 200319"},"PeriodicalIF":4.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144086923","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 : 2025-06-01Epub 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.
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