Preclinical Models of Laryngeal Papillomavirus Infection: A Scoping Review

Abstract

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

The Larynx is Protected from Secondary and Vertical Papillomavirus Infection in Immunocompetent Mice

“…Preclinical models are needed to further understand RRP disease pathogenesis and to develop medical treatments. In vitro models of human RRP typically retain HPV DNA only in the short term 3 . Animal models of laryngeal papillomavirus infection can retain viral DNA and disease phenotypes for months to years, 3 making these models an attractive option for modeling human RRP.…”