An Experimental Model of Human Recurrent Respiratory Papillomatosis: A Bridge to Clinical Insights

Uloza, Virgilijus; Kuzminienė, Alina; Palubinskienė, Jolita; Balnytė, Ingrida; Ulozienė, Ingrida; Valančiūtė, Angelija

doi:10.1002/lary.29093

Cited by 2 publications

(5 citation statements)

References 35 publications

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“…Models of low-risk HPV-associated diseases, including RRP, are limited [ 41 ]. Current preclinical models of RRP are limited to in vitro organotypic raft culture and xenografts, which are typically used at early passages to study short-term viral and host gene expression [ 42 , 43 , 44 , 45 ]. In the sole reported experimental infection of an animal larynx with an animal papillomavirus, canine oral papillomavirus (COPV) was injected into the supraglottic laryngeal tissues of canines [ 46 ].…”

Section: Introductionmentioning

confidence: 99%

A Novel In Vivo Model of Laryngeal Papillomavirus-Associated Disease Using Mus musculus Papillomavirus

King

Bilger

Rademacher

et al. 2022

Viruses

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Recurrent respiratory papillomatosis (RRP), caused by laryngeal infection with low-risk human papillomaviruses, has devastating effects on vocal communication and quality of life. Factors in RRP onset, other than viral presence in the airway, are poorly understood. RRP research has been stalled by limited preclinical models. The only known papillomavirus able to infect laboratory mice, Mus musculus papillomavirus (MmuPV1), induces disease in a variety of tissues. We hypothesized that MmuPV1 could infect the larynx as a foundation for a preclinical model of RRP. We further hypothesized that epithelial injury would enhance the ability of MmuPV1 to cause laryngeal disease, because injury is a potential factor in RRP and promotes MmuPV1 infection in other tissues. In this report, we infected larynges of NOD scid gamma mice with MmuPV1 with and without vocal fold abrasion and measured infection and disease pathogenesis over 12 weeks. Laryngeal disease incidence and severity increased earlier in mice that underwent injury in addition to infection. However, laryngeal disease emerged in all infected mice by week 12, with or without injury. Secondary laryngeal infections and disease arose in nude mice after MmuPV1 skin infections, confirming that experimentally induced injury is dispensable for laryngeal MmuPV1 infection and disease in immunocompromised mice. Unlike RRP, lesions were relatively flat dysplasias and they could progress to cancer. Similar to RRP, MmuPV1 transcript was detected in all laryngeal disease and in clinically normal larynges. MmuPV1 capsid protein was largely absent from the larynx, but productive infection arose in a case of squamous metaplasia at the level of the cricoid cartilage. Similar to RRP, disease spread beyond the larynx to the trachea and bronchi. This first report of laryngeal MmuPV1 infection provides a foundation for a preclinical model of RRP.

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Section: Introductionmentioning

confidence: 99%

A Novel In Vivo Model of Laryngeal Papillomavirus-Associated Disease Using Mus musculus Papillomavirus

King

Bilger

Rademacher

et al. 2022

Viruses

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“…In mice, reported graft survival ranged from 80 to 100% 12,51,61,81 . In the CAM, reported survival was 73–86% 85,86 . Mouse grafts survived for 2–5 months, 12,51,61,81,82 and CAM grafts survived for 2–8 days 43,83–86 .…”

Section: Resultsmentioning

confidence: 99%

“…In the CAM, reported survival was 73–86% 85,86 . Mouse grafts survived for 2–5 months, 12,51,61,81,82 and CAM grafts survived for 2–8 days 43,83–86 . Most grafts were histologically confirmed to be papillomas, 12,51,61,81,82,84–86 and CAM grafts exhibited lesion vascularization 85,86 .…”

Section: Resultsmentioning

confidence: 99%

“…85,86 Mouse grafts survived for 2-5 months, 12,51,61,81,82 and CAM grafts survived for 2-8 days. 43,[83][84][85][86] Most grafts were histologically confirmed to be papillomas, 12,51,61,81,82,[84][85][86] and CAM grafts exhibited lesion vascularization. 85,86 Disease phenotype was further confirmed in one mouse xenograft study by lesion regression in response to bevacizumab.…”

Section: Glottic Larynxmentioning

confidence: 99%

“…43,[83][84][85][86] Most grafts were histologically confirmed to be papillomas, 12,51,61,81,82,[84][85][86] and CAM grafts exhibited lesion vascularization. 85,86 Disease phenotype was further confirmed in one mouse xenograft study by lesion regression in response to bevacizumab. 12 Some mouse grafts retained HPV DNA 12,81,82 but lacked viral protein 81 and new virions, 82 and viral DNA was lost after passaging.…”

Section: Glottic Larynxmentioning

confidence: 99%

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Preclinical Models of Laryngeal Papillomavirus Infection: A Scoping Review

et al. 2023

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ObjectiveLaryngeal human papillomavirus (HPV) infection causes recurrent respiratory papillomatosis (RRP) and accounts for up to 25% of laryngeal cancers. Lack of satisfactory preclinical models is one reason that treatments for these diseases are limited. We sought to assess the literature describing preclinical models of laryngeal papillomavirus infection.Data SourcesPubMed, Web of Science, and Scopus were searched from the inception of database through October 2022.Review MethodsStudies searched were screened by two investigators. Eligible studies were peer‐reviewed, published in English, presented original data, and described attempted models of laryngeal papillomavirus infection. Data examined included type of papillomavirus, infection model, and results including success rate, disease phenotype, and viral retention.ResultsAfter screening 440 citations and 138 full‐text studies, 77 studies published between 1923 and 2022 were included. Models used low‐risk HPV or RRP (n = 51 studies), high‐risk HPV or laryngeal cancer (n = 16), both low‐ and high‐risk HPV (n = 1), and animal papillomaviruses (n = 9). For RRP, 2D and 3D cell culture models and xenografts retained disease phenotypes and HPV DNA in the short term. Two laryngeal cancer cell lines were consistently HPV‐positive in multiple studies. Animal laryngeal infections with animal papillomaviruses resulted in disease and long‐term retention of viral DNA.ConclusionsLaryngeal papillomavirus infection models have been researched for 100 years and primarily involve low‐risk HPV. Most models lose viral DNA after a short duration. Future work is needed to model persistent and recurrent diseases, consistent with RRP and HPV‐positive laryngeal cancer.Level of EvidenceN/A Laryngoscope, 2023

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An Experimental Model of Human Recurrent Respiratory Papillomatosis: A Bridge to Clinical Insights

Cited by 2 publications

References 35 publications

A Novel In Vivo Model of Laryngeal Papillomavirus-Associated Disease Using Mus musculus Papillomavirus

A Novel In Vivo Model of Laryngeal Papillomavirus-Associated Disease Using Mus musculus Papillomavirus

Preclinical Models of Laryngeal Papillomavirus Infection: A Scoping Review

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