{"title":"Characterization of HPV subtypes in invasive cervical cancer in Botswana patients using a pan-pathogen microarray technology","authors":"Surbhi Grover , Tyler Seckar , Le Gao , Rohini Bhatia , Xiang Lin , Nicola Zetola , Doreen Ramogola-Masire , Erle Robertson","doi":"10.1016/j.tvr.2023.200262","DOIUrl":"10.1016/j.tvr.2023.200262","url":null,"abstract":"<div><p>Human papillomavirus (HPV) plays a significant role in the development of cervical cancers in the setting of co-infection with HIV. Botswana has a high prevalence of HIV and cervical cancer. In this study, we investigated the distribution of HPV subtypes in cervical cancer biopsy samples from patients in Botswana using a highly sensitive pan-pathogen microarray technology, PathoChip, to detect both high- (HR-HPV) and low-risk HPV (LR-HPV) subtypes in women living with HIV (WLWH) and women living without HIV. We analyzed samples from 168 patients, of which 73% (n = 123) were WLWH with a median CD4 count of 479.5 cells/μL. Five HR-HPV subtypes were detected in the cohort: HPV 16, 18, 26, 34, and 53. The most prevalent subtypes were HPV 26 (96%) and HPV 34 (92%); 86% of WLWH (n = 106) had co-infection with four or more HR-HPV subtypes compared to 67% (n = 30) of women without HIV (p < 0.01). We detected 66 LR-HPV subtypes among all cervical cancer patients, with HPV 6b and 48 being most prevalent. Notably, signatures for LR-HPV subtypes 10, 41, 90, and 129 were only detected in WLWH. Signal intensity for HPV 18 was significantly weaker in WLWH with CD4 levels ≤200 cells/μL as compared to patients with >200 cells/μL and HIV-negative patients. Although the majority of cervical cancer specimens in this cohort were determined to have multiple HPV infections, the most prevalent HR-HPV subtypes (HPV 26 and HPV34) found in these cervical cancer samples are not covered in the current HPV vaccines. Though no conclusions can be made on the direct carcinogenicity of these subtypes the results do underlie the need for continued screening for prevention of cervical cancer.</p></div>","PeriodicalId":52381,"journal":{"name":"Tumour Virus Research","volume":"15 ","pages":"Article 200262"},"PeriodicalIF":4.3,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/1a/dc/main.PMC10239018.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9973750","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}
Olga Vladimirova , Samantha Soldan , Chenhe Su , Andrew Kossenkov , Owen Ngalamika , For Yue Tso , John T. West , Charles Wood , Paul M. Lieberman
{"title":"Elevated iNOS and 3′-nitrotyrosine in Kaposi's Sarcoma tumors and mouse model","authors":"Olga Vladimirova , Samantha Soldan , Chenhe Su , Andrew Kossenkov , Owen Ngalamika , For Yue Tso , John T. West , Charles Wood , Paul M. Lieberman","doi":"10.1016/j.tvr.2023.200259","DOIUrl":"10.1016/j.tvr.2023.200259","url":null,"abstract":"<div><p>Kaposi's Sarcoma (KS) is a heterogenous, multifocal vascular malignancy caused by the human herpesvirus 8 (HHV8), also known as Kaposi's Sarcoma-Associated Herpesvirus (KSHV). Here, we show that KS lesions express iNOS/NOS2 broadly throughout KS lesions, with enrichment in LANA positive spindle cells. The iNOS byproduct 3-nitrotyrosine is also enriched in LANA positive tumor cells and colocalizes with a fraction of LANA-nuclear bodies. We show that iNOS is highly expressed in the L1T3/mSLK tumor model of KS. iNOS expression correlated with KSHV lytic cycle gene expression, which was elevated in late-stage tumors (>4 weeks) but to a lesser degree in early stage (1 week) xenografts. Further, we show that L1T3/mSLK tumor growth is sensitive to an inhibitor of nitric oxide, L-NMMA. L-NMMA treatment reduced KSHV gene expression and perturbed cellular gene pathways relating to oxidative phosphorylation and mitochondrial dysfunction. These finding suggest that iNOS is expressed in KSHV infected endothelial-transformed tumor cells in KS, that iNOS expression depends on tumor microenvironment stress conditions, and that iNOS enzymatic activity contributes to KS tumor growth.</p></div>","PeriodicalId":52381,"journal":{"name":"Tumour Virus Research","volume":"15 ","pages":"Article 200259"},"PeriodicalIF":4.3,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/42/b4/main.PMC10009278.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10136025","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}
{"title":"Human papillomavirus genomics: Understanding carcinogenicity","authors":"Chase W. Nelson , Lisa Mirabello","doi":"10.1016/j.tvr.2023.200258","DOIUrl":"10.1016/j.tvr.2023.200258","url":null,"abstract":"<div><p>Human papillomavirus (HPV) causes virtually all cervical cancers and many cancers at other anatomical sites in both men and women. However, only 12 of 448 known HPV types are currently classified as carcinogens, and even the most carcinogenic type — HPV16 — only rarely leads to cancer. HPV is therefore necessary but insufficient for cervical cancer, with other contributing factors including host and viral genetics. Over the last decade, HPV whole genome sequencing has established that even fine-scale within-type HPV variation influences precancer/cancer risks, and that these risks vary by histology and host race/ethnicity. In this review, we place these findings in the context of the HPV life cycle and evolution at various levels of viral diversity: between-type, within-type, and within-host. We also discuss key concepts necessary for interpreting HPV genomic data, including features of the viral genome; events leading to carcinogenesis; the role of APOBEC3 in HPV infection and evolution; and methodologies that use deep (high-coverage) sequencing to characterize within-host variation, as opposed to relying on a single representative (consensus) sequence. Given the continued high burden of HPV-associated cancers, understanding HPV carcinogenicity remains important for better understanding, preventing, and treating cancers attributable to infection.</p></div>","PeriodicalId":52381,"journal":{"name":"Tumour Virus Research","volume":"15 ","pages":"Article 200258"},"PeriodicalIF":4.3,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10063409/pdf/main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9592012","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}
{"title":"Tegument proteins of Epstein-Barr virus: Diverse functions, complex networks, and oncogenesis","authors":"Takayuki Murata","doi":"10.1016/j.tvr.2023.200260","DOIUrl":"10.1016/j.tvr.2023.200260","url":null,"abstract":"<div><p>The tegument is the structure between the envelope and nucleocapsid of herpesvirus particles. Viral (and cellular) proteins accumulate to create the layers of the tegument. Some Epstein-Barr virus (EBV) tegument proteins are conserved widely in Herpesviridae, but others are shared only by members of the gamma-herpesvirus subfamily. As the interface to envelope and nucleocapsid, the tegument functions in virion morphogenesis and budding of the nucleocapsid during progeny production. When a virus particle enters a cell, enzymes such as kinase and deubiquitinase, and transcriptional activators are released from the virion to promote virus infection. Moreover, some EBV tegument proteins are involved in oncogenesis. Here, we summarize the roles of EBV tegument proteins, in comparison to those of other herpesviruses.</p></div>","PeriodicalId":52381,"journal":{"name":"Tumour Virus Research","volume":"15 ","pages":"Article 200260"},"PeriodicalIF":4.3,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10200993/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9601638","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}
{"title":"Unresolved issues in the management of human papillomavirus-associated mucosal high-grade pre-cancers","authors":"Charles JN. Lacey","doi":"10.1016/j.tvr.2022.200250","DOIUrl":"10.1016/j.tvr.2022.200250","url":null,"abstract":"<div><p>This article reviews human papillomavirus-associated mucosal high-grade pre-cancers and their management. It examines pre-cancer classification systems, the natural history of HPV-associated pre-cancers, the various types of management and treatment for HPV pre-cancers, the various mucosal site-specific considerations, and then some of the unresolved issues. Different conclusions are reached for each of the relevant mucosal sites, which are cervix, vagina, vulva, anus, penis and oro-pharynx, and indeed there are differing volumes of evidence relating to each of these sites, and thus differing degrees of certainty/uncertainty in the recommendations.</p></div>","PeriodicalId":52381,"journal":{"name":"Tumour Virus Research","volume":"15 ","pages":"Article 200250"},"PeriodicalIF":4.3,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/6c/a7/main.PMC9880239.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9604180","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}
Asmaa Mohamed Fteah , Ali Abdel Rahim , Afaf Ahmed AbdelHady , Hanan Shawky , Mohamed A Elrefaiy , Doaa Mamdouh Aly
{"title":"Association of PNPLA3 (rs738409) & TM6SF2 (rs58542926) and ATG16L1 (rs2241880) genetic variants with susceptibility to hepatocellular carcinoma in a group of Egyptian patients with HCV-induced liver cirrhosis","authors":"Asmaa Mohamed Fteah , Ali Abdel Rahim , Afaf Ahmed AbdelHady , Hanan Shawky , Mohamed A Elrefaiy , Doaa Mamdouh Aly","doi":"10.1016/j.tvr.2023.200256","DOIUrl":"10.1016/j.tvr.2023.200256","url":null,"abstract":"","PeriodicalId":52381,"journal":{"name":"Tumour Virus Research","volume":"15 ","pages":"Article 200256"},"PeriodicalIF":4.3,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/1d/91/main.PMC9975679.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9598337","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}
Wing-Hang Ip, Luca D. Bertzbach, Thomas Speiseder, Thomas Dobner
{"title":"The adenoviral E4orf3/4 is a regulatory polypeptide with cell transforming properties in vitro","authors":"Wing-Hang Ip, Luca D. Bertzbach, Thomas Speiseder, Thomas Dobner","doi":"10.1016/j.tvr.2023.200254","DOIUrl":"10.1016/j.tvr.2023.200254","url":null,"abstract":"<div><p>The human adenovirus species C type 5 (HAdV-C5) early region 4 (E4) encodes several distinct polypeptides, defined as E4orf1 to E4orf6/7 according to the order and arrangement of the corresponding open reading frames (ORFs). All E4 gene products operate through a complex network of interactions with key viral and cellular regulatory proteins involved in transcription, apoptosis, cell cycle control, and DNA repair. Here, we generated a set of virus mutants carrying point mutations in the individual E4 genes. The phenotypic characterizations of these mutants revealed that mutations of these ORFs had no or only moderate effects on virus replication. Even a triple mutant that fails to produce E4orf3, E4orf4, and the yet uncharacterized alternatively spliced E4orf3/4 fusion protein, was replicating to wild type levels. The E4orf3/4 protein consists of the N-terminal 33 amino acid residues from E4orf3 and the C-terminal 28 amino acid residues from E4orf4. Intriguingly, we found that, similar to E4orf3, E4orf3/4 possesses properties that support the E1A/E1B-induced transformation of primary rodent cells. These results identify and functionally characterize E4orf3/4 and conclude that E4orf3/4 is another E4 region protein that is dispensable for virus replication but promotes the E1A/E1B-induced transformation of primary rodent cells.</p></div>","PeriodicalId":52381,"journal":{"name":"Tumour Virus Research","volume":"15 ","pages":"Article 200254"},"PeriodicalIF":4.3,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10258410/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9624248","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}
Robert van der Geize , Natalie Methorst , Maarten Niemantsverdriet
{"title":"Detection of high-risk HPV in FFPE specimens of various tumours using the BD Onclarity™ HPV Assay","authors":"Robert van der Geize , Natalie Methorst , Maarten Niemantsverdriet","doi":"10.1016/j.tvr.2022.200243","DOIUrl":"10.1016/j.tvr.2022.200243","url":null,"abstract":"<div><p>Analysis of high-risk HPV status on formalin-fixed paraffin-embedded (FFPE) tissue material is valuable for cervical-, head and neck-, anogenital- and other types of cancer, but commercial HPV assays have been developed specifically for cervix swab cells. We evaluated the BD Onclarity™ HPV Assay for the detection of high-risk HPV on an assortment of relevant FFPE tissues with known HPV status. Detection of high-risk HPV types using the BD Onclarity™ HPV Assay in FFPE specimens was easy and accurate.</p></div>","PeriodicalId":52381,"journal":{"name":"Tumour Virus Research","volume":"14 ","pages":"Article 200243"},"PeriodicalIF":4.3,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/bc/6f/main.PMC9218226.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10514842","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}
{"title":"HPV and head and neck cancers: Towards early diagnosis and prevention","authors":"Luisa Galati , Susanna Chiocca , Daria Duca , Marta Tagliabue , Cindy Simoens , Tarik Gheit , Marc Arbyn , Massimo Tommasino","doi":"10.1016/j.tvr.2022.200245","DOIUrl":"10.1016/j.tvr.2022.200245","url":null,"abstract":"<div><p>Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide with an increasing trend of its incidence. Alcohol consumption, smoking, and viral infections, such as the mucosal high-risk (HR) human papillomaviruses (HPVs) are major risk factors for HNSCC development. In particular, HR HPVs are mainly associated with a subset of oropharyngeal squamous cell carcinoma (OPSCC), while other head and neck sites are marginally affected by HPV infection. HPV16 is the most frequently HR HPV type associated with HNSCC. In contrast to the cervix, no screening programs or identifiable pre-malignant lesions have been characterized for HPV-related HNSCC. Therefore, identification of general diagnostic algorithms and HPV biomarkers that could facilitate the early diagnosis, disease evolution and recurrence for HPV-driven HNSCCs are urgently needed. We herein review the role of HPV in HNSCC with a focus on epidemiology, biology, applied diagnostic algorithms and available biomarkers in body fluids as early diagnostic tools in HPV-driven HNSCCs.</p></div>","PeriodicalId":52381,"journal":{"name":"Tumour Virus Research","volume":"14 ","pages":"Article 200245"},"PeriodicalIF":4.3,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/4a/e5/main.PMC9420391.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10514877","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}