Comparative Analysis of Virus-Associated and Virus-Negative Tumors: Epidemiological, Genomic, and Therapeutic Insights

An estimated 15%-20% of human cancers are linked to infections, primarily caused by 23 carcinogenic viruses, with a higher incidence in developing countries. Our comparative analysis of virus-positive and virus-negative tumors in nine cancers associated with five viruses revealed a higher frequency of virus-positive tumors in males and geographic differences in incidence. Genomic analysis of 1,971 tumors showed that virus-positive tumors have a lower somatic mutation burden, distinct mutation signatures, and specific driver gene mutations. Virus-positive cases had fewer mutations in TP53, CDKN2A, and deletions of 9p21.3/CDKN2A-CDKN1A, but more mutations in RNA helicases DDX3X and EIF4A1. Clinical trials of PD-(L)1 inhibitors indicated a higher treatment response rate in virus-positive cases, especially in gastric cancer and head and neck squamous cell carcinoma. These findings highlight important epidemiological, genetic, and therapeutic trends in virus-associated cancers.