The Emerging Role of Human Papillomavirus in Shaping the Breast Tumor Microenvironment
Gabriel Romulo Parente da Silva, Isabela Duarte de Farias, Elisa Fotin Genn Barros, Gabriela Vitória de Araujo, Beatriz Eda de Oliveira Isídio, Marcelo Miranda da Silva, Isabelle Silva Simões, Pedro Henrique Bezerra Fontes, Nathálya Lima de Queiroz, Isabella Luiza Ralph de Oliveira, Bianca de França São Marcos, Daffany Luana dos Santos, Vanessa Emanuelle Pereira Santos, Antonio Carlos De FreitasBreast cancer is a heterogeneous disease influenced by genetic, hormonal, environmental, and biological factors. Among potential biological contributors, Human Papillomavirus (HPV) has attracted increasing attention due to its established oncogenic role in other malignancies. Although the association between HPV and breast cancer remains controversial, emerging evidence suggests that viral oncoproteins may modulate key components of the breast tumor microenvironment (TME). HPV oncoproteins E5, E6, and E7 have been associated with the regulation of inflammatory signaling, immune responses, extracellular matrix remodeling, and activation of oncogenic pathways, including JAK/STAT, PI3K/AKT/mTOR, and NF-κB. These alterations may promote chronic inflammation, immune evasion, angiogenesis, and tumor progression. This review discusses current evidence regarding the relationship between HPV infection and the breast TME, highlighting potential mechanisms through which the virus may influence breast cancer biology. While definitive evidence supporting a causal role of HPV in breast carcinogenesis is still lacking, available findings indicate that HPV may act as an important modulator of the breast tumor microenvironment, representing a promising area for future translational and therapeutic research.