Genomic landscape of virus-associated cancers

Area of Science:

• Oncology
• Virology
• Genomics

Background:

• Approximately 15%-20% of human cancers are linked to viral infections.
• The global incidence of virus-associated cancers varies, disproportionately affecting developing nations.

Purpose of the Study:

• To comparatively analyze virus-positive and virus-negative tumors across nine cancer types linked to five distinct viruses.
• To investigate the epidemiological, genomic, and therapeutic implications of viral infections in cancer.

Main Methods:

• Comparative analysis of 1971 virus-positive and virus-negative tumors.
• Genomic profiling, including mutation burden, mutational signatures, and driver gene analysis.
• Analysis of clinical trial data for PD-(L)1 inhibitor response rates and immune cell infiltration.

Main Results:

• Virus-positive tumors were more frequent in males, with significant geographic variations.
• Virus-positive tumors exhibited a lower somatic mutation burden, unique mutation signatures, and altered driver gene mutations (e.g., fewer TP53/CDKN2A mutations, more DDX3X/EIF4A1 mutations).
• Virus-positivity correlated with higher response rates to PD-(L)1 inhibitors, increased CD8+ T cell infiltration, and T cell receptor clonal selection, particularly in gastric and head and neck cancers.

Conclusions:

• Viral infections significantly impact cancer development, genetics, and immune microenvironment.
• Virus-associated cancers present distinct genomic landscapes compared to their virus-negative counterparts.
• Virus-positivity may predict a favorable response to immune checkpoint inhibitor therapy in specific cancer types.