A Mouse Model of Oropharyngeal Papillomavirus-Induced Neoplasia Using Novel Tools for Infection and Nasal Anesthesia

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Abstract

Human head and neck cancers that develop from the squamous cells of the oropharynx (Oropharyngeal Squamous Cell Carcinomas or OPSCC) are commonly associated with the papillomavirus infection. A papillomavirus infection-based mouse model of oropharyngeal tumorigenesis would be valuable for studying the development and treatment of these tumors. We have developed an efficient system using the mouse papillomavirus (MmuPV1) to generate dysplastic oropharyngeal lesions, including tumors, in the soft palate and the base of the tongue of two immune-deficient strains of mice. To maximize efficiency and safety during infection and endoscopy, we have designed a nose cone for isoflurane-induced anesthesia that takes advantage of a mouse’s need to breathe nasally and has a large window for oral manipulations. To reach and infect the oropharynx efficiently, we have repurposed the Greer Pick allergy testing device as a virus delivery tool. We show that the Pick can be used to infect the epithelium of the soft palate and the base of the tongue of mice directly, without prior scarification. The ability to induce and track oropharyngeal papillomavirus-induced tumors in the mouse, easily and robustly, will facilitate the study of oropharyngeal tumorigenesis and potential treatments.

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Mice anesthesia, analgesia, and care, Part I: anesthetic considerations in preclinical research.

S. Gargiulo, A. Greco, M. Gramanzini … (2012)

Animal experiments are necessary for a better understanding of diseases and for developing new therapeutic strategies. The mouse (Mus musculus) is currently the most popular laboratory animal in biomedical research. Experimental procedures on animals often require anesthesia and/or analgesia to obtain adequate immobilization and to reduce stress or pain. Mice anesthesia is challenging for several reasons including the animals' size, metabolic rate, and the high risk of hypothermia and hypoglycemia. Moreover, anesthetic agents influence physiological parameters, further interfering with experimental results. Small animal imaging procedures are increasingly used in biomedical research both because the animals allow in vivo monitoring and because they are readily available for longitudinal and noninvasive studies as well as investigations into the evolution of diseases and the effects of new therapies. Anesthesia must adapt to the imaging technique, the procedure length, and the aim of the study. The purpose of this article is to review the existing literature on anesthetic protocols adopted in mice for molecular imaging studies and to report our experience.

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Squamous cell carcinoma in situ at oropharyngeal and hypopharyngeal mucosal sites.

Chikatoshi Katada, Manabu Muto, Shigeaki Yoshida … (2004)

Head and neck squamous cell carcinoma typically is diagnosed at an advanced stage, and the prognosis for patients with this type of malignancy is poor. Detection of these lesions at an earlier stage (e.g., as carcinoma in situ) would be of clear benefit to patients. However, it has been extremely difficult to detect carcinoma in situ at head and neck mucosal sites during routine endoscopy, even after numerous passes of the endoscope through the oral cavity and the pharynx. The current clinical investigation was performed during routine endoscopic screening or surveillance procedures. The authors used a novel optical technique, known as narrowband imaging (NBI) that allows noninvasive visualization of the microvascular structure of an organ's surface using reflected light. Between April 2002 and August 2003, 34 consecutive superficial lesions were found in 18 patients. Multifocal carcinoma was found in 5 patients (28%). The median age of the patients examined was 59.5 years (range, 43-71 years), and 83% of all patients were male. All lesions exhibited a microvascular proliferation pattern on magnified NBI. Thirteen patients with a combined total of 29 lesions underwent endoscopic resection under general anesthesia. The pyriform sinus was the most frequent primary site (66%; 19 of 29 lesions). The median tumor diameter was 20 mm (range, 1.3-40 mm). Twenty-one lesions (72%) were histologically confirmed to be carcinoma in situ, and the remaining lesions showed evidence of microinvasion (0.05-1 mm) beneath the epithelium. Vascular invasion was observed in only one lesion. The median hospital stay was 10 days (range, 4-18 days). All patients were discharged without severe complications. After a median follow-up period of 8 months (range, 1-16 months), there were no cases of local disease recurrence. The authors stress the importance of endoscopic detection of superficial carcinoma at oropharyngeal and hypopharyngeal mucosal sites. NBI is a promising and potentially powerful tool for identifying carcinomas at an earlier stage during routine endoscopic examination. Copyright 2004 American Cancer Society.

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Is Open Access

Mucosal and Cutaneous Human Papillomavirus Infections and Cancer Biology

Tarik Gheit (2019)

Papillomaviridae is a family of small non-enveloped icosahedral viruses with double-stranded circular DNA. More than 200 different human papillomaviruses (HPVs) have been listed so far. Based on epidemiological data, a subgroup of alphapapillomaviruses (alpha HPVs) was referred to as high-risk (HR) HPV types. HR HPVs are the etiological agents of anogenital cancer and a subset of head and neck cancers. The cutaneous HPV types, mainly from beta and gamma genera, are widely present on the surface of the skin in the general population. However, there is growing evidence of an etiological role of betapapillomaviruses (beta HPVs) in non-melanoma skin cancer (NMSC), together with ultraviolet (UV) radiation. Studies performed on mucosal HR HPV types, such as 16 and 18, showed that both oncoproteins E6 and E7 play a key role in cervical cancer by altering pathways involved in the host immune response to establish a persistent infection and by promoting cellular transformation. Continuous expression of E6 and E7 of mucosal HR HPV types is essential to initiate and to maintain the cellular transformation process, whereas expression of E6 and E7 of cutaneous HPV types is not required for the maintenance of the skin cancer phenotype. Beta HPV types appear to play a role in the initiation of skin carcinogenesis, by exacerbating the accumulation of UV radiation-induced DNA breaks and somatic mutations (the hit-and-run mechanism), and they would therefore act as facilitators rather than direct actors in NMSC. In this review, the natural history of HPV infection and the transforming properties of various HPV genera will be described, with a particular focus on describing the state of knowledge about the role of cutaneous HPV types in NMSC.

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Journal

Journal ID (nlm-ta): Viruses

Journal ID (iso-abbrev): Viruses

Journal ID (publisher-id): viruses

Title: Viruses

Publisher: MDPI

ISSN (Electronic): 1999-4915

Publication date (Electronic): 16 April 2020

Publication date Collection: April 2020

Volume: 12

Issue: 4

Electronic Location Identifier: 450

Affiliations

[1 ]McArdle Laboratory for Cancer Research, University of Wisconsin, Madison, WI 53705, USA; bilger@ 123456oncology.wisc.edu (A.B.); mbarthel@ 123456wisc.edu (M.V.B.); etward@ 123456wisc.edu (E.T.W.-S.)

[2 ]Department of Surgery, University of Wisconsin, Madison, WI 53705, USA; kingr@ 123456surgery.wisc.edu (R.E.K.); thibeaul@ 123456surgery.wisc.edu (S.L.T.)

[3 ]Department of Biomedical Engineering, University of Wisconsin, Madison, WI 53705, USA; schroeder26@ 123456wisc.edu (J.P.S.); piette2@ 123456wisc.edu (J.T.P.); lhinshaw@ 123456wisc.edu (L.A.H.); akurth3@ 123456wisc.edu (A.D.K.); ralramahi@ 123456wisc.edu (R.W.A.); kmasters@ 123456wisc.edu (K.S.M.)

[4 ]Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, WI 53705, USA; buehler2@ 123456wisc.edu

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[* ]Correspondence: plambert@ 123456wisc.edu

Author information

Andrea Bilger https://orcid.org/0000-0002-4838-4731

Renee E. King https://orcid.org/0000-0002-6540-3834

Kristyn S. Masters https://orcid.org/0000-0001-6911-3116

Article

Publisher ID: viruses-12-00450

DOI: 10.3390/v12040450

PMC ID: 7232375

PubMed ID: 32316091

SO-VID: 0745d86d-f4d7-4db0-8421-3df6a549b094

License:

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

A Mouse Model of Oropharyngeal Papillomavirus-Induced Neoplasia Using Novel Tools for Infection and Nasal Anesthesia

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Decoding Infection and Transmission

Most cited references 22

Mice anesthesia, analgesia, and care, Part I: anesthetic considerations in preclinical research.

Squamous cell carcinoma in situ at oropharyngeal and hypopharyngeal mucosal sites.

Mucosal and Cutaneous Human Papillomavirus Infections and Cancer Biology

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