Medical Research: Emerging Concepts and Applications Vol. 2

Chronic infection remains one of the few causes of human cancer for which the causal chain is understood at molecular resolution and for which primary prevention has already been demonstrated at population scale. Roughly one in eight incident cancers worldwide is attributable to an infectious agent, and the affected burden falls disproportionately on low-income and middle-income settings. Existing reviews of this field have tended to be organised agent by agent, to treat the two vaccine-preventable exemplars as templates for the remaining agents, and to give limited attention to the methodological architecture on which attributable-burden estimates rest. This review examines the field as a single evidentiary problem rather than a catalogue of pathogens. It evaluates how attributable fractions are constructed and where they are most fragile, compares direct and indirect mechanistic routes and asks what each route implies for the feasibility of vaccine-based control, and appraises the strength of the evidence that vaccination alters cancer incidence rather than surrogate endpoints. Human papillomavirus and hepatitis B virus vaccination are supported by registry-linked and cohort evidence extending to invasive cancer, although the two programmes differ substantially in the maturity, granularity and generalisability of that evidence. For hepatitis C virus, Helicobacter pylori, Epstein–Barr virus, Kaposi sarcoma herpesvirus, human T-lymphotropic virus type 1, Merkel cell polyomavirus and the carcinogenic helminths, prevention rests on treatment, screening or sanitation, and the barriers to vaccination are biological and economic rather than merely technical. Persistent uncertainties include the durability of reduced-dose schedules, the transferability of eradication-trial results to low-incidence populations, the causal status of candidate agents identified through sequencing, and the reasons why coverage failures rather than efficacy failures now dominate the gap between what is achievable and what is achieved. Prevention research priorities should shift towards implementation, long-horizon endpoints and settings where the burden is greatest.