Causes and Consequences of HPV Integration in Head and Neck Squamous Cell Carcinomas: State of the Art

SIMPLE SUMMARY: In human papillomavirus (HPV) associated head and neck squamous cell carcinomas (HNSCC) s, the HPV genome is commonly found integrated in the human genome. The event of viral–human genome integration may act as a driver of carcinogenesis. Hence, it is vital to assess the viral integration status of a tumor. In this review, current and emerging techniques for integration detection are thoroughly discussed with their advantages and disadvantages. Additionally, the review also discusses the causes of HPV integration into the cellular genome, as well as its ramifications, impacting possible clinical implications. ABSTRACT: A constantly increasing incidence in high-risk Human Papillomaviruses (HPV)s driven head and neck squamous cell carcinomas (HNSCC)s, especially of oropharyngeal origin, is being observed. During persistent infections, viral DNA integration into the host genome may occur. Studies are examining if the physical status of the virus (episomal vs. integration) affects carcinogenesis and eventually has further-reaching consequences on disease progression and outcome. Here, we review the literature of the most recent five years focusing on the impact of HPV integration in HNSCCs, covering aspects of detection techniques used (from PCR up to NGS approaches), integration loci identified, and associations with genomic and clinical data. The consequences of HPV integration in the human genome, including the methylation status and deregulation of genes involved in cell signaling pathways, immune evasion, and response to therapy, are also summarized.