# Understanding the Role of HAART in the Progression of HPV-Associated Oral Cancer

> **NIH NIH R01** · PENNSYLVANIA STATE UNIV HERSHEY MED CTR · 2024 · $525,486

## Abstract

SUMMARY
The overall incidence of HPV+ head and neck squamous cell carcinoma (HNSCC) has exhibited an increasing
trend over the last few decades, and has now in the U.S. overtaken cervical cancer as the most common site of
HPV related cancer. The majority of patients present with advanced-stage HNSCC are without a clinical history
of pre-malignancy. Because there is a paucity of pre-cancer clinical samples the studying the steps of cancer
progression that would provide an understanding of the carcinogenic we have developed an in vitro progression
model. Interestingly, HPV+ patients compared to HPV negative (HPV-) patients have an improved overall
prognosis and greater disease-free survival, attributed partly to a better response to radio- and/or chemotherapy.
The mechanisms and natural history of oral HPV infection and carcinogenic progression are poorly understood.
 Men and women infected with human immunodeficiency virus (HIV) have higher rates of HPV16
infection, longer persistence of HPV16, increased incidence of HNSCC, poorer prognosis, as well as
more recurrences after definitive therapy. There have been substantial changes in the burden of cancer
affecting HIV-infected individuals in the U.S. during the period spanning the introduction of highly active anti-
retroviral therapy (HAART). Scaling-up of HAART therapy has dramatically increased the life expectancy of
people living with HIV (PLHIV). As a result of these temporal changes, non-AIDS-defining cancers have come
to comprise the majority of cancers in HIV-infected persons during the HAART era. Among these emerging
malignancies, HPV-associated cancers of the oral cavity/pharynx increased significantly following an
AIDS diagnosis. Most patients with HIV/HPV co-infections on HAART therapy have reduced risk of developing
HPV-associated cancers such as cervical cancer but have a higher risk of developing HPV-associated oral
cancers the risk is suggested to be due to longer life expectancy as a results of HAART therapy. But it is unclear
why HAART therapy may have different effects on HPV+ HNCSCC versus HPV+ cervical cancers.
 Our overarching hypothesis is that HAART therapy affects the progression of HPV+ HNC. This increases
the numbers of PLHIV who have persistent oral HPV infections that progress to HNCSCC, poorer prognosis,
and death. We propose to focus on three areas to test this hypothesis.
Specific Aim 1. Analyze HAART induced differences of HPV carcinogenic propensity in oral epithelial
cells. Specific Aim 2: Investigate the effect of HAART on carcinogenic markers and metabolic pathways
associated with HPV+ HNSCC. Specific Aim 3: Study the effect of HAART on glycolysis versus
mitochondrial respiration.

## Key facts

- **NIH application ID:** 10840458
- **Project number:** 5R01DE032212-03
- **Recipient organization:** PENNSYLVANIA STATE UNIV HERSHEY MED CTR
- **Principal Investigator:** Craig M Meyers
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $525,486
- **Award type:** 5
- **Project period:** 2022-07-11 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10840458

## Citation

> US National Institutes of Health, RePORTER application 10840458, Understanding the Role of HAART in the Progression of HPV-Associated Oral Cancer (5R01DE032212-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10840458. Licensed CC0.

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