# Vocal fold epithelial barrier and proliferation in laryngeal papillomatosis

> **NIH NIH F31** · UNIVERSITY OF WISCONSIN-MADISON · 2020 · $32,553

## Abstract

ABSTRACT
Recurrent respiratory papillomatosis (RRP) is a highly morbid upper airway disease caused by non-cancer-
causing human papillomavirus (HPV) types 6 and 11. RRP is characterized by quickly growing clustered
epithelial lesions in the larynx and upper airway. Although lesions are histologically benign, they cause voice
disorders and can result in life-threatening airway obstruction, particularly in children. Repeated surgical
excision of lesions required as often as every few months to maintain breathing can cause vocal fold scar and
further impair voice function. Vaccination is preventive only. There is no cure for established HPV infection or
for RRP. RRP research has been limited by the lack of a preclinical model. Papillomaviruses require layered
epithelium to complete their life cycle. Clinically, RRP progression includes regression and recurrence of
lesions. These aspects of disease are best captured using animal models, which have been limited since
papillomaviruses are also species-specific. The recent discovery of murine papillomavirus MmuPV1 has
created novel opportunities to model papillomavirus infection in genetically modifiable laboratory animals.
However, there are no studies of MmuPV1 in vocal folds and/or larynx to date. The overall goal of this work is
to define the interaction between vocal fold epithelial injury and papillomavirus infection using a novel murine
model of laryngeal papillomatosis. Aim 1 will investigate the role of mechanical injury on MmuPV1 disease
progression in murine larynx using longitudinal measures of disease burden and viral load, as well as
localizing viral RNA and assembly of infectious particles within tissue at multiple timepoints during wound
healing. In parallel, Aim 2 will characterize changes in epithelial morphology, barrier integrity, and cell
proliferation and death induced by papillomavirus infection throughout wound healing. Our central hypothesis
is that epithelial injury will facilitate viral infection, and that infection will disrupt normal epithelial integrity and
cell turnover. By clarifying the role of vocal fold injury in onset of laryngeal papillomatosis and the initial effects
of papillomatosis on vocal fold epithelium, completion of our specific aims will have a significant impact on
laryngology and virology. This proposal will result in a novel preclinical model of RRP that will facilitate further
study of disease persistence and recurrence, including the role of the immune system, and will ultimately be
used to develop innovative prevention and treatment strategies for this intractable and devastating disease.

## Key facts

- **NIH application ID:** 9933774
- **Project number:** 5F31DC018184-02
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Renee King
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $32,553
- **Award type:** 5
- **Project period:** 2019-09-01 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9933774

## Citation

> US National Institutes of Health, RePORTER application 9933774, Vocal fold epithelial barrier and proliferation in laryngeal papillomatosis (5F31DC018184-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9933774. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*