This review, by integrating 34 global studies, provides comprehensive evidence for the association between carcinogenic human papillomavirus and breast cancer and proposes a groundbreaking mechanistic explanation: HPV may drive tumorigenesis via a unique “low viral load, high carcinogenic impact” mode by activating the host APOBEC3B enzyme to induce genomic instability. This evidence concerns the gene APOBEC3B and breast carcinoma.