Human papillomavirus and host genetic polymorphisms in carcinogenesis: a systematic review and meta-analysis

Abstract

Background: As the role of human papillomavirus (HPV) in carcinogenesis continues to rise, the role of genetic factors that modify this risk have become increasingly important. In this study, we reviewed the literature for associations between polymorphisms and HPV in carcinogenesis.

Objective: To identify any associations of genetic polymorphisms with oncogenic HPV in carcinogenesis and to evaluate the methodology used.

Study design: Systematic literature review of HPV, genetic polymorphisms, and cancer risk. Odds ratios (OR), interaction terms, and p-values were tabulated. Meta-analyses and measures of heterogeneity were estimated using RevMan 5.1.

Results: The cervix was the most frequently studied cancer site followed by the head and neck. Overall risk of cancer (cancer vs. control) was the most common comparison, whereas reports of initiation (pre-cancer vs. control) and progression (cancer vs. pre-cancer) were rare. Case-series and joint-effect of HPV and genotype on risk was evaluated frequently, but the independent effect of either risk factor alone was rarely provided. P53-Arg72Pro was the most commonly studied polymorphism studied. No consistent interaction was detected by meta-analysis in the HPV(+) [OR 0.98 (0.55-1.76)] or the HPV(-) [OR 1.10 (0.76-1.60)] subsets in head and neck cancer risk. Polymorphisms in genes known to encode proteins that physically interact with HPV were infrequently studied.

Conclusion: No consistent polymorphism-HPV interactions were observed. Study design, choice of candidate polymorphisms/genes, and a focus on overall risk rather than any specific portions of the carcinogenic pathway may have contributed to lack of significant findings.

Keywords: Cancer; Cervix; Head and neck; Human papillomavirus; Interaction; Polymorphism.