# HPV alternative splicing in cervical cancer radiation response

> **NIH NIH K22** · WASHINGTON UNIVERSITY · 2022 · $156,656

## Abstract

PROJECT SUMMARY/ABSTRACT
Human papillomavirus (HPV) infection is the primary cause of cervical carcinoma. Locally advanced cervical
cancer (LACC) is incurable with a high recurrence rate after standard-of-care chemoradiation therapy (CRT).
High-risk HPV genotypes have evolved complex regulatory strategies to tightly control viral gene expression
and alternative splicing. Recent studies indicate that some alternatively spliced HPV genes have different
functions in cervical tumor replication and oncogenesis than their full-length oncogene counterparts. The ratio
of full-length and alternatively spliced HPV transcripts can vary in cervical tumors harboring different high-risk
HPV genotypes. We manually inspected whole transcriptome sequencing (RNA-seq) data and discovered
recurrent HPV-human gene fusions containing alternatively spliced HPV transcripts and long intergenic non-
protein-coding human RNAs (lncRNA). HPV alternative splicing is important in cervical cancer biology;
however, it is still unclear whether alternatively spliced HPV transcripts affect the chemoradiation response in
cervical cancer patients. The proposed research will determine whether alternatively spliced HPV transcripts
have prognostic and mechanistic significance for patient outcomes in cervical cancer. Specifically, we will
determine whether alternatively spliced HPV transcripts modulate radiation response using HPV-transformed
cervical cancer cells and telomerase-reverse-transcriptase (hTERT) transformed cervical epithelial cells. We
will also evaluate whether alternatively spliced HPV transcripts can serve as biomarkers for different HPV
genotypes using cDNA capture sequencing data and clinical data from an established cohort of LACC patients
uniformly treated with curative-intent CRT. Finally, we will develop novel algorithms to identify viral-host gene
fusions and examine their functional consequences using RNA-seq data and clinical outcome data. Successful
completion of this translational research will identify alternatively spliced HPV transcripts as accurate
prognostic molecular biomarkers and suitable novel targets in LACC. Establishing the mechanistic function of
HPV alternative splicing in cervical cancer radiation response will ultimately facilitate the development of
optimized therapies and improve patient outcomes.

## Key facts

- **NIH application ID:** 10308435
- **Project number:** 5K22CA237839-02
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Jin Zhang
- **Activity code:** K22 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $156,656
- **Award type:** 5
- **Project period:** 2020-12-01 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10308435

## Citation

> US National Institutes of Health, RePORTER application 10308435, HPV alternative splicing in cervical cancer radiation response (5K22CA237839-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10308435. Licensed CC0.

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