Human papillomavirus infection increases the risk of breast carcinoma: a large-scale systemic review and meta-analysis of case-control studies

Background: Breast carcinoma (BC) is a cancer with a high morbidity rate, but the mechanisms by which it develops are never clear. There has been speculation regarding the potential relationships between breast cancer and local HPV infections for some time, and although much clinical research supports this hypothesis, some research results disprove the association. Therefore, the association is still inconclusive. Methods: We performed the data collection by searching the database PubMed, Embase, Cochrane Library and Web of science. In addition, 22 sites were added manually. After carefully selection, the pooled odds rate of 37 included case control studies was calculated. Subgroup analysis, publication bias and trim & fill analysis were conducted to make the result more reliable. Results: The analysis of 37 case control studies containing 3,607 BC cases and 1,728 controls showed obviously increase of BC risk with human papillomavirus (HPV) positive [summary odds ratio (SOR) =6.22, 95% confidence interval 4.25 to 9.12; P=0.0002]. Subgroup analysis proved three high risk HPV types (HPV16, 18 and 33) were positively correlated to BC. Conclusions: This systemic review and meta-analysis provide the evidence for HPV infection as a potential risk factor in BC, while the mechanism of this hypothesis still needs further evaluation.