[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-345046-105":59,"doc-detail-345046-en":130},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":123,"head_meta":125,"extra_data":127,"updated_unix":129},105,"en","the-utility-of-fibroblast-co-culture-for-the-maintenance-of-episomes-in-human-papillomavirus-associated-cancer-models","The utility of fibroblast co-culture for the maintenance of episomes in human papillomavirus-associated cancer models","","Human papillomavirus-associated head and neck squamous cell carcinomas (HPV+ HNSCCs) lack early diagnostics and their incidence continues to rise. HPV16 is found in roughly 90% of HPV+ oropharyngeal cancers (HPV+ OPCs), and many tumors retain episomal viral genomes, yet episomal HPV16+ OPC cell lines remain scarce. The study shows UMSCC104s rapidly integrate and lose E2 in standard monoculture, with later lots fully integrated. Fibroblast co-culture is proposed to stabilize episomal status by supporting viral and host genome stability.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/the-utility-of-fibroblast-co-culture-for-the-maintenance-of-episomes-in-human-papillomavirus-associated-cancer-models/345046/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/the-utility-of-fibroblast-co-culture-for-the-maintenance-of-episomes-in-human-papillomavirus-associated-cancer-models/345046.png","ImageObject",300,407,{"name":92,"@type":93},"Ivy","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-09-23","2026-09-22",true,{"@type":102,"interactionType":103,"userInteractionCount":8},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"Why are accurate HPV+ oropharyngeal cancer models needed?","Question",{"text":112,"@type":113},"HPV+ HNSCCs continue to increase in incidence and lack early diagnostics, so improved preclinical models are required to study the disease and develop better therapeutic approaches.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What conflict exists in the literature about UMSCC104 cells?",{"text":117,"@type":113},"UMSCC104s were initially reported as episomal, but published reports disagree on whether these cells retain episomal genomes or have integrated viral DNA.",{"name":119,"@type":110,"acceptedAnswer":120},"How do the authors propose maintaining episomes in cancer models?",{"text":121,"@type":113},"They propose fibroblast co-culture methods, adapted from HPV+ keratinocyte models, to preserve episomal status by supporting stability of both viral and host genomes.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},345046,1790161769,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":8,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":34,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":144},549758252649,"https://ap-avatar.wpscdn.com/avatar/8000253669c5317157?_k=1778319167496531819","| Virology | Opinion/Hypothesis  \nThe utility offibroblast co-culture for the maintenance of episomes in human papillomavirus-associated cancer models  \nAustin J. Witt,1 Rachel L. Lewis,1 Xu Wang,1 Phoebe Bridy,1 Jenny Roe,1 Iain M. Morgan,1,2 Claire D. James,1,2 Molly L. Bristol1,2 AUTHOR AFFILIATIONS See affiliation list on p. 6.  \nABSTRACT Human papillomavirus-associated head and neck squamous cell carcinomas (HPV+ HNSCCs) lack early diagnostics and continue to rise in incidence. HPV16 has been detected in ~90% of HPV+ oropharyngeal cancers (HPV+ OPCs), an anatomical subset of HNSCC, with the majority retaining episomal viral genomes. Despite this, existing episomal HPV16+ OPC cell lines are especially scarce. UMSCC104s were initially reported as episomal; however, the literature contains conflicting reports regarding the genome status of these cells. We now show that UMSCC104s rapidly undergo integration and E2 loss under standard monoculture, and later lots are fully integrated. These findings resolve prior discrepancies and underscore the instability of episomes in monoculture. Accurate models of HPV-driven cancers are critically needed. We propose fibroblast co-culture methods, traditionally utilized for HPV+ keratinocyte models, as a strategy topreserve episomal status in cancer models by supporting viral and host genome stability.  \nKEYWORDS fibroblasts, HPV, oropharyngeal cancer, HNSCC, co-culture  \nH uman papillomaviruses (HPVs) are oncogenic viruses responsible for approximately  \n5% of human cancers, including a growing subset of head and neck squamous cell carcinomas (HNSCCs) (1–3) . Among these, HPV+ oropharyngeal cancers (HPV+ OPCs) have risen sharply in incidence, with HPV16 detected in as high as 90% of cases (3, 4) . While HPV+ OPC patients generally have favorable prognoses, the substantial longterm morbidities among survivors highlight the urgent need for improved therapeutic approaches (4–6) . To this point, there is a significant need for appropriate preclinical models to study this disease.  \nHPV episomal genome status is prognostically significant in HNSCC, and more than 70% of HPV+ OPC patient tumors retain extrachromosomal viral episomes (6– 9) . Episomal status is associated with significantly improved overall survival, when compared to tumors with integrated genomes or HPV-negative disease (6) . Conversely, most existing HPV16+ HNSCC cell lines are derived from non-oropharyngeal sites and contain integrated viral genomes, thus limiting their clinical relevance (3, 6–11) . The successful establishment of HNSCC cell lines has been shown to correlate with poor prognosis for the associated patients (9, 12) . This may partially account for the selective availability of cell lines harboring integrated viral genomes, as they have poor prognostics and in turn may be more likely to yield stable cell lines than those retaining episomal HPV. We also suggest that the traditional monoculture approach commonly utilized for cancer cells may likewise hinder the establishment of episomal lines, consistent with knowledge that fibroblast co-culture is essential for episomal maintenance in other epithelial models (13) . This idea is further supported by our recent observation that 50% of a set of HPV16+ OPC patient-derived xenografts (PDXs) retain episomal genomes, potentially due to their consistent maintenance adjacent to mouse stroma (3) .  \nUpon initial HPV infection, viral genomes are maintained as low-copy extrachromosomal episomes in basal keratinocytes (13) . In vivo, infected basal keratinocytes are  \nEditor Ira J. Blader, Virginia-Maryland College of Veterinary Medicine, Blacksburg, Virginia, USA  \nAddress correspondence to Molly L. Bristol,  \nadjacent to the stroma, and fibroblasts are a major component in this microenvironment (14) . Fibroblasts are noted to secrete essential growth factors that regulate both keratinocyte proliferation and differentiation (10, 13) . In vitro, episomes are generally unstabl","cbCaiiob5CNJ7nGi","https://ap.wps.com/l/cbCaiiob5CNJ7nGi","pdf",659857,"English","# Abstract\n# Keywords\n# Introduction and rationale\n## Clinical need for preclinical models\n## Prognostic value of episomal HPV genomes\n# Background on episome maintenance\n## Role of fibroblast co-culture and feeder layers\n# Results\n## Rapid episome loss in UMSCC104s in monoculture","[{\"question\":\"Why are accurate HPV+ oropharyngeal cancer models needed?\",\"answer\":\"HPV+ HNSCCs continue to increase in incidence and lack early diagnostics, so improved preclinical models are required to study the disease and develop better therapeutic approaches.\"},{\"question\":\"What conflict exists in the literature about UMSCC104 cells?\",\"answer\":\"UMSCC104s were initially reported as episomal, but published reports disagree on whether these cells retain episomal genomes or have integrated viral DNA.\"},{\"question\":\"How do the authors propose maintaining episomes in cancer models?\",\"answer\":\"They propose fibroblast co-culture methods, adapted from HPV+ keratinocyte models, to preserve episomal status by supporting stability of both viral and host genomes.\"}]","The utility of fibroblast co-culture for the maintenance of episomes in human papillomavirus-associated cancer models | PDF",1790056352,18]