# Project 1 - Characterize the Mechanism by Which Papillomaviruses Evade Host Immunity

> **NIH NIH P01** · UNIVERSITY OF WISCONSIN-MADISON · 2024 · $426,371

## Abstract

PROJECT 1 – PROJECT SUMMARY/ABSTRACT
Project 1. Characterize the Mechanism by Which Papillomaviruses Evade Host Immunity
Paul Lambert, Project Leader; Paul Ahlquist and Paul Sondel, Co-Leaders
A subset of human papillomaviruses (HPVs) cause 5% of human cancers including the majority of cervical
cancers, which is an AIDS-defining malignancy. During the current funding period, we discovered a host factor
induced by papillomaviruses that contributes to the ability of this virus to evade host immune responses, allowing
it to establish persistent infections that can lead to cancer. This discovery was made using a mouse
papillomavirus infection model. Evidence supports the hypothesis that high-risk anogenital HPVs use this same
mechanism. We further discovered that this host factor contributes to resistance to immune checkpoint blockade
immunotherapy (ICI) in both mouse and human head and neck cancers. In this project we will explore further
the mechanisms underlying immune evasion by HPV using a new model for inducible expression of HPV16
oncogenes in immunocompetent mice that better models HPV-induced carcinogenesis in humans, focusing on
anal cancer because its frequency of occurrence is increasing, especially amongst people living with HIV
(PLWH). During the current funding period, we also discovered that estrogen, which we and others have
previously determined contributes to HPV-mediated cervical carcinogenesis, promotes persistent infection by
mouse papillomavirus at least in part by suppressing host immunity, leading to increased severity of
cervicovaginal neoplasia including cancer in mice. We describe experiments to determine how estrogen affects
host immunity, and how to block it to improve response to ICI. The studies described in this project are designed
to learn how to convert HPV-associated cancers that tend to be immunologically cold, ICI-unresponsive tumors
to immunologically hot, ICI-responsive tumors, with the ultimate goal to translate our findings to the clinic.

## Key facts

- **NIH application ID:** 10837987
- **Project number:** 2P01CA022443-46A1
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Paul F. Lambert
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $426,371
- **Award type:** 2
- **Project period:** 1997-02-01 → 2029-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10837987

## Citation

> US National Institutes of Health, RePORTER application 10837987, Project 1 - Characterize the Mechanism by Which Papillomaviruses Evade Host Immunity (2P01CA022443-46A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10837987. Licensed CC0.

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