ORO-HPV-INT Project: Is HPV-DNA integration into the host genome linked to outcomes in oropharyngeal cancer patients?

• Applicants: Dr. Kerstin Becker; Privatdozent Dr. Christian Hübbers; Professor Dr. Jens Peter Klußmann
• Subject Area: Otolaryngology, Phoniatrics and Audiology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 562441374

Human papillomavirus (HPV) is a pivotal risk factor for the development of oropharyngeal squamous cell carcinoma (OPSCC), with an increasing incidence reported in several countries. With a prevalence of more than 80%, high-risk HPV16 is the most common type detected in OPSCC. Studies have shown that when HPV DNA incorporates into the host's genome, it significantly impacts the expression of cellular genes in the host. These genetic alterations are associated with poor outcomes, including reduced treatment efficacy and a higher likelihood of cancer spreading to distant sites. Due to the need for high-quality DNA in current methodologies, most published findings are based on analyses of fresh-frozen samples, which are not typically available in routine practice. We have recently introduced the Targeted Locus Amplification (TLA) method based on proximity ligation followed by next-generation sequencing (NGS), which reliably identifies HPV integration even in fragmented DNA present in routinely available FFPE tissue. The proposed grant application seeks to investigate the role of HPV host genome integration in a statistically reliable cohort of HPV-positive OPSCC, reflecting the full spectrum of this disease, including samples from which only a limited quantity of material is available for analysis as a result of the small tumour size or the exclusive availability of biopsy samples. This study aims to understand the link between viral host genome integration, and the resulting consequences for host genome organization and subsequent processing of the modified genome. This grant covers the following objectives: 1) To assess the status of HPV integration in a statistically robust cohort of HPV-positive OPSCC patients to analyse the impact of HPV integration on disease outcome and therapy response. 2) To determine the effects of HPV integration on the genome of the host cell and subsequent processing of this modified genome. 3) To determine whether other simple and cost-effective markers can predict integration status in addition to direct identification of HPV integration. The aim of this study is to reliably estimate whether viral host genome integration influences prognosis in HPV-positive OPSCC and whether knowledge of integration status could lead to personalised treatment decisions.

• DFG Programme: Research Grants