Introduction:
The implication of viral infection in alterations of vital cellular pathways and genomic integration and thus, human carcinogenesis is well documented in molecular epidemiology studies. EBV and CMV are two of the most studied human viruses for potential association with cancer risk, progression, and outcome. The contradicting reports as for the etiologic role of these viruses in breast cancer entailed the conduction of the current meta-analysis

Material and methods:
A thorough comprehensive electronic search was performed using PubMed, EMBASE, and Web of Science databases for relevant publications until February 28, 2021 based on predefined eligibility criteria. Extracted data from eligible studies were used to calculate the pooled effect size, heterogeneity, publication bias, sensitivity, and subgroup analyses for both viruses independently. Meta-analyses were performed using Prometa 3 software.

Results:
For EBV, a total of 19 studies were included, while 8 studies were included for CMV. A significantly high risk of breast cancer with EBV infection (OR = 5.04, 95%CI: 3.44 – 7.39, P < 0.05), a similar, though smaller risk with CMV (OR = 4.53, 95%CI: 2.04 – 10.03, P < 0.05). EBV studies in which viral genetic material was detected in fresh breast cancer tissue showed higher risk compared to studies relied upon FFPE specimen. Conversely, for CMV, the FFPE studies showed a higher risk compared to studies relying upon fresh breast cancer tissues.

Conclusions:
It can be inferred that infection with either of the two viruses increases the risk of breast cancer, suggesting an etiologic role of these viruses in breast carcinogenesis.