Oncolytic virus therapy for hepatocellular carcinoma: A bibliometric analysis of research landscapes, hotspots, and clinical transformation trends from 2000 to mid-2025

This study aimed to systematically analyze the research status, hotspots, and trends of oncolytic virotherapy (OV) for hepatocellular carcinoma (HCC) from 2000 to mid-2025, scientifically predict future directions, facilitate clinical translation, and provide a reference for subsequent studies in this field. Based on the Web of Science Core Collection and Scopus databases, bibliometric methods were adopted combined with visualization analyses using R software (version 4.5.1), VOSviewer (version 1.6.19), and CiteSpace (version 6.4.R1). A total of 341 publications were retrieved from the WoSCC database and 624 from the Scopus database. Based on the combined analysis of both databases, the field exhibited a continuous upward trend in publication output. The top four countries in both databases were China, the USA, Germany, and Korea. China ranked first globally with 152 publications in WoSCC and 212 in Scopus, but its international co-authorship rates (13.2% and 17.5%, respectively) were markedly lower than those of the USA (34.4% and 34.9%) and Korea (40.0% and 33.3%). Molecular Therapy is the most influential core journal in this field. Research hotspots focus on four main areas: the mechanisms of oncolytic virus therapy for HCC, the evolution of genetically engineered armed vectors, combination therapies involving oncolytic viruses, and the challenges and breakthroughs in clinical translation. Future advances in this field will likely focus on three key directions: (1) optimizing transgene expression to balance antiviral and antitumor immunity; (2) developing personalized therapeutic strategies based on biomarkers such as immune cell subsets; (3) advancing clinical validation and regulatory approval of combination regimens through multicenter clinical studies. OV for HCC has entered a new integrated stage featuring mechanistic innovation, vector optimization, and precise combination therapy. The clear future directions can provide a well-defined roadmap for clinical translation, which is expected to yield more effective novel therapeutic strategies for HCC.