Researchers report that individuals carrying HPV were more than twice as likely to develop CRC as those without the virus, with the strongest associations seen for the high-risk HPV16 strain, among Asian populations, and in studies using formalin-fixed paraffin-embedded (FFPE) tissue samples. The authors suggest that incorporating viral profiling into
colorectal cancer screening could help pinpoint people at greatest risk and guide targeted prevention strategies.
The systematic review and meta-analysis were led by Mengqi Yang and colleagues from the Faculty of Pharmacy and Pharmaceutical Science at Monash University, Australia. Following PRISMA 2020 guidelines, the team combed through PubMed, Embase, Web of Science, and the Cochrane Library up to May 2025, focusing on observational case–control and cross-sectional studies. Data from 20 eligible studies—covering 1,424 CRC cases and 1,363 controls—were pooled to clarify whether HPV infection contributes to colorectal cancer development.
The key findings of the study:
- The pooled odds ratio was 2.39, showing that HPV-positive individuals had more than double the risk of colorectal cancer compared with HPV-negative individuals.
- There was no significant heterogeneity across the included studies (I² = 0%), strengthening the reliability of the findings.
- The association was strongest in Asian populations, where the odds ratio increased to 3.73.
- Detection using formalin-fixed paraffin-embedded (FFPE) tissue samples showed an odds ratio of 3.56.
- Studies focusing only on the high-risk HPV16 genotype reported even higher effect sizes than those assessing mixed or unspecified HPV strains.
To ensure reliability, the investigators performed sensitivity analyses, including leave-one-out testing, which confirmed the robustness of the results. Meta-regression further underscored the role of geographic region and HPV genotype as key modifiers of risk. While Egger’s test hinted at minimal small-study bias, the funnel plot demonstrated no significant publication bias overall.
HPV is already recognized as a major cause of cervical, anal, and certain head-and-neck cancers, but its role in colorectal cancer has been debated. These updated findings strengthen the evidence that the virus may act as an oncogenic driver beyond the anogenital tract. The authors emphasize the importance of region-specific and genotype-aware screening strategies, particularly in populations with high HPV prevalence or limited access to preventive healthcare.
Clinicians, the study notes, may want to consider viral profiling as part of comprehensive colorectal cancer prevention and early detection programs. Tailoring screening to account for HPV infection—especially the HPV16 strain—could improve identification of high-risk patients and open doors for interventions such as vaccination and vigilant surveillance.
"By consolidating data from diverse global studies, this meta-analysis offers compelling evidence that HPV infection is a significant, independent risk factor for colorectal cancer. The findings highlight an emerging frontier in cancer prevention, where understanding viral contributions may help reduce the global burden of CRC through targeted public health initiatives and improved clinical practice," the authors concluded.
Reference:
Yang, Mengqi MSa; Huo, Yujia MSb,c,d; Huasng, Yedong MD, PhDe; He, Wenjun MD, PhDf; Luo, Qingyu PhDg,h; Zhang, Lin MD, PhDb,c,d,*. Human papillomavirus (HPV) infection and prevalence of colorectal cancer: an updated systematic review and meta-analysis of global data. International Journal of Surgery ():10.1097/JS9.0000000000003426, September 11, 2025. | DOI: 10.1097/JS9.0000000000003426
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