Human Papillomaviruses and Breast Cancer: A Systematic Review and Meta‑analysis

Breast cancer (BC) is the leading malignancy worldwide. The association between human papillomavirus (HPV) and BC is debatable. The present systematic review and meta-analysis aimed to assess the prevalence of HPV DNA in malignant breast tumors. An extensive search of the PubMed and SCOPUS databases was carried out for case-control studies published between January 1, 2003 and January 7, 2023, which compared HPV DNA detection in breast tissue specimens of female patients with BC and women with absent or benign breast disorders. Once the initial title/abstract screening was completed by two independent investigators, the full texts of the included studies from that stage were reviewed by the aforementioned investigators to determine if they should be included in the present study. Data extraction was independently conducted by two investigators. A third investigator was consulted to resolve disagreements through free discussion. MedCalc was used for quantitative synthesis. The significance of association was estimated by pooled odds ratios (ORs) with 95% confidence intervals (CIs) calculated using the random-effects model. A total of 23 primary studies, including 3,243 subjects (2,027 patients and 1,216 controls), were eligible for quantitative analysis. HPV prevalence in patients with BC and controls was 21.95 and 8.96%, respectively. The prevalence of HPV differed significantly between the two groups (OR 3.83; 95% CI 2.03-7.25; P<0.01). Heterogeneity among studies was quantified using the I index which was 69.57% (95% CI 51.89-80.75). The risk of bias was assessed using an appropriate tool contributed by the CLARITY Group at McMaster University. Seven studies had a low risk of bias, 15 studies had a moderate risk of bias and only one study had a serious risk of bias. These results reinforce the hypothesis that HPV is involved in BC development and progression, indicating a possible role of HPV vaccination in BC prevention.