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Updated: Jan 22, 2026

Chromogenic In Situ Hybridization as a Tool for HPV-Related Head and Neck Cancer Diagnosis
Published on: June 14, 2019
Radiosensitization approaches for HPV-positive and HPV-negative head and neck squamous carcinomas
Rüveyda Dok1, Marieke Bamps1, Mary Glorieux1
1Department of Oncology, KU Leuven, University of Leuven, Leuven, Belgium.
Abstract:
Radiotherapy is one of the most used treatment approaches for head and neck squamous cell carcinoma (HNSCC). Targeted inhibition of DNA repair machinery has the potential to improve treatment response by tailoring treatment to cancer cells lacking specific DNA repair pathways. Human papillomavirus (HPV)-negative and HPV-positive HNSCCs respond differently to radiotherapy treatment, suggesting that different approaches of DNA repair inhibition should be employed for these HNSCC groups. Here, we searched for optimal radiosensitization approaches for HPV-positive and HPV-negative HNSCCs by performing a targeted CRISPR-Cas9 screen. We found that inhibition of base excision repair resulted in a better radiotherapy response in HPV-positive HNSCC, which is correlated with upregulation of genes involved in base excision repair. In contrast, inhibition of nonhomologous end-joining and mismatch repair showed strong effects in both HNSCC groups. We validated the screen results by combining radiotherapy with targeted inhibition of DNA repair in several preclinical models including primary and recurrent patient-derived HNSCC xenografts. These findings underline the importance of stratifying HNSCC patients for combination treatments.
Insights
Targeted DNA repair inhibition enhances radiotherapy for head and neck cancers. Base excision repair inhibition benefits HPV-positive tumors, while other repair pathway inhibitors work for both HPV-positive and HPV-negative HNSCC.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Genetics
Background:
- Radiotherapy is a primary treatment for head and neck squamous cell carcinoma (HNSCC).
- Tailoring radiotherapy by inhibiting DNA repair pathways shows promise for improving treatment outcomes.
- Human papillomavirus (HPV)-positive and HPV-negative HNSCC exhibit differential responses to radiotherapy.
Purpose of the Study:
- To identify optimal radiosensitization strategies for HPV-positive and HPV-negative HNSCC.
- To investigate the potential of targeted DNA repair inhibition in combination with radiotherapy.
- To stratify HNSCC patients for personalized combination treatments.
Main Methods:
- A targeted CRISPR-Cas9 screen was employed to identify effective radiosensitization targets.
- Preclinical models, including patient-derived HNSCC xenografts, were used for validation.
- Combination therapies involving radiotherapy and targeted DNA repair inhibitors were tested.
Main Results:
- Inhibition of base excision repair improved radiotherapy response in HPV-positive HNSCC, correlating with gene expression.
- Inhibition of nonhomologous end-joining and mismatch repair demonstrated efficacy in both HPV-positive and HPV-negative HNSCC.
- Validated findings in preclinical models confirmed the differential and broad effects of targeting specific DNA repair pathways.
Conclusions:
- Stratifying HNSCC patients based on HPV status is crucial for optimizing combination treatment strategies.
- Targeted inhibition of specific DNA repair pathways offers a promising approach to enhance radiotherapy efficacy.
- The study highlights the importance of understanding DNA repair mechanisms in HNSCC for developing personalized therapies.
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