Breast cancer risk factors include lifestyle, genetic–hormonal influences, and viral infections. Human papillomavirus (HPV), known primarily as the etiological agent of cervical cancer, also appears active in breast carcinogenesis, as evidenced in our study of 56 patients from northeastern Brazil. We assessed the clinical and sociodemographic characteristics, correlating them with various breast cancer tumor types. HPV detection involved amplifying the L1 region, with viral load measured using the E2/E6 ratio and viral activity indicated by E5 oncogene expression. Predominantly, patients over 56 years of age with healthy lifestyles showed a high incidence of invasive ductal carcinoma and triple-negative breast cancer. HPV was detected in 35.7% of cases, mostly HPV16, which is associated with high viral loads (80 copies per cell) and significant E5 expression. These results hint at a possible link between HPV and breast carcinogenesis, necessitating further studies to explore this association and the underlying viral mechanisms.

Head and neck cancer (HNC) is the sixth most prevalent type of cancer worldwide and is associated with low five-year survival rates. Alcoholism and smoking are the main risk factors associated with the development of head and neck cancer (HNC). However, Human Papillomavirus (HPV) infection has been reported as a significant risk factor, particularly for the oropharyngeal subset. In these cases, patients with HPV-positive HNC exhibit a better clinical prognosis; however, resistance to chemotherapy has been frequently reported. The carcinogenic activity of HPV is related to the viral oncoproteins E5, E6, and E7. E5 has been associated with immune evasion mechanisms and modulation of the tumor microenvironment, which appears to be linked to the virus’s resistance to chemotherapeutic treatments. Here, we review the potential of HPV E5 in targeted therapy for HNC and discuss relevant data regarding the activity of this oncoprotein in head and neck carcinogenesis.

Breast cancer is among the most prevalent and deadly types of cancer worldwide. Viral infections have been investigated as contributing factors in breast carcinogenesis, including infections by high-risk genotypes of human papillomavirus (HPV). Although viral DNA has been detected in breast tumors, the role of HPV activity in this type of cancer remains poorly understood. HPV oncogenes interact with various host genes, including those involved in the JAK/STAT signaling pathway. This pathway is associated with the regulation of gene expression related to the tumor microenvironment, and understanding how HPV oncogenes interact with JAK/STAT components may provide insights into the relationship between the virus and breast cancer development. In this study, we assessed the differential expression of the JAK/STAT pathway in MDA-MB-231 cells individually transfected with the E5, E6, and E7 oncogenes of HPV16. The results revealed downregulation of STAT4 in the presence of the E5, E6, and E7 oncogenes. Notably, cells transfected with E5 alone exhibited upregulation of JAK2, STAT3, and STAT6, whereas transfection with E6 and E7 resulted in their downregulation. These findings highlight the underexplored role of the E5 oncogene in contrast to the more extensively studied E6 and E7. Our results support the hypothesis that HPV oncogenes actively modulate the expression of genes involved in the tumor microenvironment in breast cancer.

Aim: Breast cancer is the most prevalent malignant tumor among women. Human papillomavirus (HPV) has been detected in breast tumors since the 1990s, and beyond its oncogenic potential, therapy resistance driven by viral immune evasion in non-anogenital tumors, such as oropharyngeal cancers, highlights the need to investigate viral activity in breast tissues. Among high-risk HPV types, HPV16 is one of the most prevalent and exhibits the highest carcinogenic potential. Therefore, this study aimed to evaluate the expression of HPV16 oncogenes E5, E6, and E7 in breast tumors, as well as the modulation of the PI3K/AKT/mTOR signaling pathway associated with viral activity. Methods: A total of 92 breast cancer patients were included after Ethics Committee approval. Clinical data were obtained from medical records. RNA was extracted from formalin-fixed, paraffin-embedded tissues and reverse-transcribed into cDNA. Transcripts of HPV oncogenes (E5, E6, and E7), components of the PI3K/AKT/mTOR pathway, and regulatory genes (EGFR and PTEN) were quantified by RT-qPCR. Gene expression levels were calculated using the ΔCt method. Results: Forty-eight samples met RNA quality criteria and were included in the expression analysis. Among these, 77.08% showed expression of at least one viral oncogene, with E5 being the most frequently expressed. The PI3K/AKT/mTOR pathway was modulated in HPV-positive samples, with increased PI3K expression and decreased mTOR expression. Notably, the high expression of E5—associated with immune evasion—combined with reduced mTOR expression suggests that HPV16 status may influence therapeutic response in breast cancer patients. Conclusions: These findings reinforce the importance of further studies investigating HPV activity in breast tumors to better understand its biological and clinical impact.

Breast 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.