Expanded Basal Compartment and Disrupted Barrier in Vocal Fold Epithelium Infected with Mouse Papillomavirus MmuPV1

King, R. J.; Ward-Shaw, Ella; Hu, Rong; Lambert, Paul F.; Thibeault, Susan L.

doi:10.3390/v14051059

Cited by 3 publications

(2 citation statements)

References 112 publications

(154 reference statements)

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“…In two studies, immunocompromised mice were infected with Mus musculus papillomavirus (MmuPV1; Table V). 11,121 One MmuPV1 study was a follow‐up using tissues from the other 121 . MmuPV1 induced laryngeal dysplasia and SCC that persisted at least 12 weeks 11 .…”

Section: Resultsmentioning

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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Section: Resultsmentioning

confidence: 99%

“…11,121 One MmuPV1 study was a follow-up using tissues from the other. 121 MmuPV1 induced laryngeal dysplasia and SCC that persisted at least 12 weeks. 11 Lesions were positive for MmuPV1 DNA and transcripts, but negative for capsid protein.…”

Section: Models Of Laryngeal Scc or Laryngeal High-risk Hpv Infectionmentioning

confidence: 99%

Preclinical Models of Laryngeal Papillomavirus Infection: A Scoping Review

et al. 2023

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Intraperitoneal delivery of cannabidiol (CBD) and Δ9-tetrahydocannabinol (THC) promotes papillomavirus infections in athymic nude mice

Brendle,

Li,

Sun

et al. 2025

Tumour Virus Research

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Monitoring mouse papillomavirus-associated cancer development using longitudinal Pap smear screening

Atkins,

Uslu,

et al. 2024

mBio

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A substantial percentage of the population remains at risk for cervical cancer due to pre-existing human papillomavirus (HPV) infections, despite prophylactic vaccines. Early diagnosis and treatment are crucial for better disease outcomes. The development of new treatments heavily relies on suitable preclinical model systems. Recently, we established a mouse papillomavirus (MmuPV1) model that is relevant to HPV genital pathogenesis. In the current study, we validated the use of Papanicolaou (Pap) smears, a valuable early diagnostic tool for detecting HPV cervical cancer, to monitor disease progression in the MmuPV1 mouse model. Biweekly cervicovaginal swabs were collected from the MmuPV1-infected mice for viral DNA quantitation and cytology assessment. The Pap smear slides were evaluated for signs of epithelial cell abnormalities using the 2014 Bethesda system criteria. Tissues from the infected mice were harvested at various times post-viral infection for additional histological and virological assays. Over time, increased viral replication was consistent with higher levels of viral DNA, and it coincided with an uptick in epithelial cell abnormalities with higher severity scores noted as early as 10 weeks after viral infection. The cytological results also correlated with the histological evaluation of tissues harvested simultaneously. Both immunocompromised and immunocompetent mice with squamous cell carcinoma (SCC) cytology also developed vaginal SCCs. Notably, samples from the MmuPV1-infected mice exhibited similar cellular abnormalities compared to the corresponding human samples at similar disease stages. Hence, Pap smear screening proves to be an effective tool for the longitudinal monitoring of disease progression in the MmuPV1 mouse model. IMPORTANCE Papanicolaou (Pap) smear has saved millions of women's lives as a valuable early screening tool for detecting human papillomavirus (HPV) cervical precancers and cancer. However, more than 200,000 women in the United States alone remain at risk for cervical cancer due to pre-existing HPV infection-induced precancers, as there are currently no effective treatments for HPV-associated precancers and cancers other than invasive procedures including a loop electrosurgical excision procedure (LEEP) to remove abnormal tissues. In the current study, we validated the use of Pap smears to monitor disease progression in our recently established mouse papillomavirus model. To the best of our knowledge, this is the first study that provides compelling evidence of applying Pap smears from cervicovaginal swabs to monitor disease progression in mice. This HPV-relevant cytology assay will enable us to develop and test novel antiviral and anti-tumor therapies using this model to eliminate HPV-associated diseases and cancers.

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Expanded Basal Compartment and Disrupted Barrier in Vocal Fold Epithelium Infected with Mouse Papillomavirus MmuPV1

Cited by 3 publications

References 112 publications

Preclinical Models of Laryngeal Papillomavirus Infection: A Scoping Review

Preclinical Models of Laryngeal Papillomavirus Infection: A Scoping Review

Intraperitoneal delivery of cannabidiol (CBD) and Δ9-tetrahydocannabinol (THC) promotes papillomavirus infections in athymic nude mice

Monitoring mouse papillomavirus-associated cancer development using longitudinal Pap smear screening

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