Genomic landscape of virus-associated cancers

Yoonhee Nam, Karen Gomez, Jean-Baptiste Reynier, Cole Khamnei, Michael Aitken, Vivian Zheng, Tenzin Lhakhang, Milena Casula, Giuseppe Palmieri, Antonio Cossu, Arnold Levine, Enrico Tiacci and Raul Rabadan ()
Additional contact information
Yoonhee Nam: Columbia University
Karen Gomez: Columbia University
Jean-Baptiste Reynier: Columbia University
Cole Khamnei: Columbia University
Michael Aitken: Columbia University
Vivian Zheng: Columbia University
Tenzin Lhakhang: Columbia University
Milena Casula: National Research Council (CNR)
Giuseppe Palmieri: National Research Council (CNR)
Antonio Cossu: University of Sassari
Arnold Levine: Institute for Advanced Study
Enrico Tiacci: University and Hospital of Perugia
Raul Rabadan: Columbia University

Nature Communications, 2025, vol. 16, issue 1, 1-16

Abstract: Abstract It has been estimated that 15%-20% of human cancers are attributable to infections, mostly by carcinogenic viruses. The incidence varies worldwide, with a majority affecting developing countries. Here, we conduct a comparative analysis of virus-positive and virus-negative tumors in nine cancers linked to five viruses. We observe a higher frequency of virus-positive tumors in males, with notable geographic differences in incidence. Our genomic analysis of 1971 tumors reveals a lower somatic burden, distinct mutation signatures, and driver gene mutations in virus-positive tumors. Compared to virus-negative cases, virus-positive cases have fewer mutations of TP53, CDKN2A, and deletions of 9p21.3/CDKN2A-CDKN1A while exhibiting more mutations in RNA helicases DDX3X and EIF4A1. Furthermore, an analysis of clinical trials of PD-(L)1 inhibitors suggests an association of virus-positivity with higher treatment response rate, particularly evident in gastric cancer and head and neck squamous cell carcinoma. Both cancer types also show evidence of increased CD8 + T cell infiltration and T cell receptor clonal selection in virus-positive tumors. These results illustrate the epidemiological, genetic, and therapeutic trends across virus-associated malignancies.

Date: 2025
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DOI: 10.1038/s41467-025-60836-9

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