HPV Integration in Head and Neck Squamous Cell Carcinomas: Cause and Consequence.

Area of Science:

• Oncology
• Virology
• Molecular Biology

Background:

• High-risk human papillomaviruses (HRHPV) are causally linked to anogenital and oropharyngeal squamous cell carcinomas (SCC).
• Key events in HRHPV-associated cancer progression include persistent infection, viral gene dysregulation, immune suppression, and chromosomal alterations.
• While cervical carcinogenesis is well-studied, early HRHPV-positive head and neck lesions are rarely detected.

Purpose of the Study:

• To summarize the causes and consequences of HPV DNA integration into host chromosomes.
• To examine the impact of HPV integration site on viral oncogene expression (E6/E7).
• To investigate the effects of HPV integration on human gene expression, cell proliferation, apoptosis, and signaling pathways.

Main Methods:

• Literature review focusing on HPV integration in carcinogenesis.
• Analysis of studies examining HPV integration sites within the host genome.
• Review of data on DNA methylation, viral load, and clinical outcomes related to HPV integration.

Main Results:

• HPV DNA integration is a frequent event in both cervical and oropharyngeal SCC (40-90%), particularly HPV16 in oropharyngeal SCC.
• Extrachromosomal (episomal) HPV DNA is present in 10-60% of HPV-positive tumors.
• HPV integration influences viral oncogene expression and host cellular processes, including proliferation and apoptosis.

Conclusions:

• HPV DNA integration is a critical driver in HRHPV-associated cancers.
• The site of HPV integration significantly affects oncogene expression and cellular pathways.
• Further research into HPV integration, methylation, viral load, and clinical outcomes is warranted.