Abstract
A causal link between Human Papillomavirus (HPV) and breast cancer (BC) remains controversial. In spite of this, the observation that HPV DNA is over-represented in the Triple Negative (TN) BC has been reported. Here we remark the high prevalence of HPV DNA (44.4%) in aggressive BC subtypes (TN and HER2+) in a population of 273 Italian women and we convey the presence of HPV DNA in the epithelial and stromal compartments by in situ hybridization. As previously reported, we also found that serum derived-extracellular vesicles (EVs) from BC affected patients contain HPV DNA. Interestingly, in one TNBC patient, the same HPV DNA type was detected in the serum-derived EVs, cervical and BC tissue samples. Then, we report that HPV DNA can be transferred by EVs to recipient BC stromal cells that show an activated phenotype (e.g., CD44, IL6 expression) and an enhanced capability to sustain mammospheres (MS) formation. These data suggest that HPV DNA vehiculated by EVs is a potential trigger for BC niche aggressiveness.
Highlights
Human Papillomavirus (HPV) is a common pathogen in oropharyngeal and ano-genital cancers [1]
We found that HPV DNA was over-represented in the Triple Negative (TN) subtype (12/27, 44.4%), in aggressive HER2+ breast cancer (BC) (15/31, 48.4 %) compared to Luminal A (LumA) (34/142, 23.9%) and Luminal B (LumB) ones (22/73, 30.1%) (Monte Carlo X square test: P = 0.0181, Figure 1C)
We found the presence of HPV16 DNA in 2 out of 9 Breast Cancer Derived-Fibroblasts (BC DFs), one from an HPV16 DNA positive TNBC and one from an HPV16 DNA positive LumB cancer (Figure 1H)
Summary
Human Papillomavirus (HPV) is a common pathogen in oropharyngeal and ano-genital cancers [1]. Circulating HPV DNA may contribute to HPV DNA spreading in unconventional site of infection. At this regard, some authors reported circulating HPV DNA in the serum of patients with HPV-associated invasive cancer [10] and as marker for disease extent and recurrence [14]. We found HPV DNA in the serum derived-extracellular vesicles (EVs) of breast pathologies affected women as well as in patient with HPV DNA positive squamous cell carcinoma of the middle rectum [15, 16]. We report that HPV DNA is associated with aggressive BC phenotypes and that HPV DNA is present in serum derived-EVs of TNBC affected patients. We showed that EVs transfer HPV DNA to BC stromal cells, which acquire an inflammatory activated phenotype
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