# HPV genomic structure in cervical cancer radiation response and recurrence detection

> **NIH NIH R37** · WASHINGTON UNIVERSITY · 2024 · $476,719

## Abstract

PROJECT SUMMARY/ABSTRACT
Cervical cancer is one of the most common cancer diagnoses among women, and treatment failure of standard
of care (SOC) chemoradiation therapy (CRT) for locally advanced cervical cancer (LACC) is as high as 30-50%.
Since recurrent and metastatic diseases are not curable or detected too late to be treatable, there is a pressing
need for pre-treatment biomarkers to identify patients at risk of CRT treatment failure and post-treatment
biomarkers to detect LACC recurrence and metastasis early. TCGA’s effort to establish pre-treatment biomarkers
for cervical cancer by molecular stratification using human genes failed to associate to patient outcomes. On the
other hand, we recently demonstrated that HPV genotypes and HPV alternative splicing affect LACC recurrence
and survival after CRT. In our preliminary data, we additionally identified a diversity of HPV genomic structures
(HPV-GS), including HPV-human gene fusions involving alternative spliced HPV exons, that affect human
oncogene expression. We hypothesize that the variance of HPV genomic structural features among LACC
patients may represent a valuable clinical sequencing application to develop LACC SOC CRT biomarkers. For
post-treatment markers, we currently use F-fluorodeoxyglucose PET/CT (FDG-PET) images at 3–6 months to
define metabolic response, which was shown in our previous publications to predict patterns of failure after
radiotherapy for cervical cancer. We hypothesize that HPV genomic features can serve as post-treatment
biomarkers for LACC recurrence and metastasis detection that are both more accurate and detectable at earlier
timepoints. To achieve these goals, we will first test whether variance in HPV-GS can be utilized to develop a
clinical pre-treatment biomarker by developing a series of novel HPV-GS analysis tools based on our expertise
in both HPV genomics and human structural variants. HPV features will be extracted from matched DNA and
RNA sequencing data, and their prognostic values will be tested using samples from our cervical tumor bank of
LACC patients uniformly treated with curative-intent CRT. Second, we will examine whether CRT-induced LACC
clonal evolution can be used to identify treatment-resistant HPV-GS as on-treatment biomarkers. A novel deep
targeted sequencing approach will be used on single-nucleotide variants (SNV) and HPV-GS to identify LACC
subclones and fit HPV-GS in the context of clonal evolution. We will also examine the mechanisms of HPV-
human gene fusions using clonogenic survival assays and other standard assays. Last, we will use our proven
highly-sensitive and flexible CAPP-Seq technology to evaluate whether circulating tumor DNA (ctDNA) can be
used to develop HPV-GS tests for early diagnosis and post-CRT recurrence detection. We expect combining
both SNVs and HPV-GS will result in an optimized application superior to using single types of features alone.
Taken together, we expect our genomic and mechanistic research on H...

## Key facts

- **NIH application ID:** 10831841
- **Project number:** 5R37CA279596-02
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Jin Zhang
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $476,719
- **Award type:** 5
- **Project period:** 2023-05-01 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10831841

## Citation

> US National Institutes of Health, RePORTER application 10831841, HPV genomic structure in cervical cancer radiation response and recurrence detection (5R37CA279596-02). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10831841. Licensed CC0.

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