Abstract
A BSTRACT The association between human papillomavirus (HPV) infection and colorectal cancer (CRC) remains a subject of active scientific debate, with significant inconsistencies in the data. This mini-review synthesizes contemporary studies (2016 - January 2026) investigating this association. The review reveals geographic heterogeneity in the prevalence of HPV DNA in CRC tissues, ranging from 0% in some European populations to over 60% in several Middle Eastern and Asian countries. Analysis indicates that a substantial portion of the discrepancy in research findings is attributable to methodological differences, particularly the use of highly sensitive polymerase chain reaction-based methods, which may yield higher detection rates than other approaches. The presence of viral DNA is insufficient to establish causality; more compelling evidence comes from the detection of transcriptionally active, integrated virus and from the expression of the E6/E7 oncoproteins. The biological plausibility of HPV’s involvement in carcinogenesis is examined, including the possibility of retrograde infection, its role in specific tumor subtypes (e.g. neuroendocrine carcinomas), the influence of co-infections (Epstein–Barr virus, polyomaviruses), and host genetics. Data from Mendelian randomization and large-scale epidemiological cohort studies partially support a causal link. Paradoxically, in some studies, the presence of HPV has been associated with a more favorable tumor immune microenvironment and improved survival. In conclusion, current evidence does not support a universal etiological role for HPV in CRC. Still, it suggests its potential as a cofactor in specific geographic regions, histological subtypes, and clinical contexts. Further standardized research focused on detecting active viral infection is required to clarify the clinical and biological significance of this association.