# Downstream effects of HPV integration on survival/metastasis in oropharyngeal cancer

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2021 · $216,973

## Abstract

ABSTRACT
The incidence of human papillomavirus associated (HPV(+)) oropharyngeal squamous cell carcinoma
(OPSCC) is rising in the US, to the point that it is now estimated to be more prevalent than cervical cancer.
There are significant disparities in OPSCC, especially with respect to recurrence and survival, which is worse
in African-American OPSCC patients compared to non-Hispanic White (NHW) OPSCC patients. Due to low
HPV vaccine use rates and the decades long latency period between HPV infection and cancer diagnosis,
HPV(+) OPSCC remains a major health concern. The 5 year survival rate for HPV(+) OPSCC patients is 80%,
significantly lower than the estimated 90% for invasive breast cancer, and the most likely reason for death is
distant metastasis. Limited data in African-Americans indicate 1.6-times worse survival compared to NHW
OPSCC, with few HPV-specific studies in this racial group. Furthermore, due to the life-long detrimental
treatment effects on quality of life for survivors, it is of great interest to identify a subset of patients who would
benefit from de-escalated treatment. Our long term goal for the parent grant is to differentiate between HPV(+)
patients who have a good prognosis and are most likely to benefit from de-escalated therapy and those who
require the standard, or a more aggressive regimen. Our group first characterized the two main subtypes of
HPV(+) OPSCC, identifying HPV integration into the host genome as the driving factor in determining tumor
subtype. We furthermore showed that HPV integration status is associated with overall survival.
In this proposal we will extend our parent grant plan to a cohort of African-American OPSCC patients from the
Louisiana Tumor Registry to study three downstream effects of HPV integration identified by our group and
others: an increase in the splicing of HPV oncogene E6 to E6*, a decrease in the tumor immune response, and
a change in cell differentiation status. Each of these effects plays a role in determining metastasis and survival,
however the mechanism of their effect and their relative contributions remain unclear. In aim 1, we will
disentangle the above three effects of HPV integration on overall and disease-specific survival using 150
African-American OSPCC tumors from the Louisiana Tumor Registry, and we will compare these tumors to our
NHW tumors from Michigan. In aim 2, we will examine the effects of the shift to expressing mainly the shorter
E6* isoform instead of full length E6 in these tumors. This was observed by us and others to increase oxidative
phosphorylation and potentially tumor mutational burden. These studies are a first critical step to
understanding the molecular consequences of HPV(+) OPSCC in African-Americans to identify avenues to
improve prognosis in this understudied group.

## Key facts

- **NIH application ID:** 10260028
- **Project number:** 3R01CA250214-02S1
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** LAURA ROZEK
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $216,973
- **Award type:** 3
- **Project period:** 2020-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10260028

## Citation

> US National Institutes of Health, RePORTER application 10260028, Downstream effects of HPV integration on survival/metastasis in oropharyngeal cancer (3R01CA250214-02S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10260028. Licensed CC0.

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