Cell-resolved virus-host programs across cancers associated with five human oncoviruses: a systematic review

<title>Abstract</title> <p>Single-cell RNA sequencing can separate transcriptional changes within a cell type from shifts in tumor composition, yet findings from virus-associated cancers remain scattered across diseases and study designs. Human single-cell RNA-sequencing studies were reviewed, including cancers associated with human papillomavirus (HPV), Epstein-Barr virus (EBV), hepatitis B virus (HBV), human T-cell leukemia virus type 1 (HTLV-1), or Merkel cell polyomavirus (MCPyV). PubMed/MEDLINE was searched for reports published from 2020 to 2 August 2026, with complementary coverage checks in Scopus and Web of Science. Seventy-five reports met the eligibility criteria (HPV, 34; EBV, 14; HBV, 18; HTLV-1, 5; MCPyV, 4). Findings did not converge on a single host-gene signature. Instead, several functions recurred in different cellular compartments: interferon responses, antigen presentation, clonal lymphocyte expansion, and B-cell or tertiary-lymphoid organization were accompanied by checkpoints, T-cell exhaustion, regulatory T cells, suppressive myeloid and stromal states, and loss of antigen presentation. Within malignant cells, viral transcript abundance was associated with differentiation, integration, proliferation, invasion, or treatment response, although these relationships varied by virus, lineage, tissue, disease stage, and therapy. More informative studies combined cell-level viral-read assignment with patient-level analysis, etiologically matched controls, spatial or longitudinal sampling, and orthogonal validation. These design features will be necessary if cell-resolved virus-host programs are to yield reproducible biomarkers.</p>