Presence of high-risk HPVs, EBV, and MMTV in human triple-negative breast cancer

Abstract

Breast cancer, the most frequent disease amongst women worldwide, accounts for the highest cancerrelated mortality rate. Triple-negative breast cancer (TNBC) subtype encompasses ~15% of all breast cancers and lack estrogen, progesterone, and HER2 receptors. Although risk factors for breast cancer are well-known, factors underpinning breast cancer onset and progression remain unknown. Recent studies suggest the plausible role of oncoviruses including human papillomaviruses (HPVs), Epstein-Barr virus (EBV), and mouse mammary tumor virus (MMTV) in breast cancer pathogenesis. However, the role of these oncoviruses in TNBC is still unclear. In the current study, we explored the status of high-risk HPVs, EBV, and MMTV in a well-defined TNBC cohort from Croatia in comparison to 16 normal/non TNBC samples (controls) using polymerase chain reaction assay. We found high-risk HPVs and EBV present in 37/70 (53%) and 25/70 (36%) of the cases, respectively. The most common HPV types are 52, 45, 31, 58 and 68. We found 16% of the samples positive for co-presence of high-risk HPVs and EBV. Moreover, our data revealed that 5/70 (7%) samples are positive for MMTV. In addition, only 2/70 (3%) samples had copresence of HPVs, EBV, and MMTV without any significant association with the clinicopathological variables. While, 6/16 (37.5%) controls were positive for HPV (p = .4), EBV was absent in all controls (0/ 16, 0%) (p = .01). In addition, we did not find the co-presence of the oncoviruses in the controls (p > .05). Nevertheless, further investigations are essential to understand the underlying mechanisms of multipleoncogenic viruses' interaction in breast carcinogenesis, especially TNBC.

Coinfection of HPVs Is Associated with Advanced Stage in Colorectal Cancer Patients from Qatar

“…Polymerase chain reaction (PCR) was performed to analyze HR HPVs in purified genomic DNA, through the use of primers specific to HR HPV types: 16, 18, 31, 33, 35, 45, 51, 52, and 59, as previously described [ 46 , 47 ]. For the internal control, GAPDH was used.…”

“…All analyses were completed as described by our group [ 46 ]. For each single experiment, we used the respective positive and negative controls reported by our group previously [ 47 ].…”

Mouse Mammary Tumor Virus (MMTV) and MMTV-like Viruses: An In-depth Look at a Controversial Issue

“…BC discovered during pregnancy or lactation is known to be very aggressive and of poor prognosis, probably because of the effect of hormones on the stimulation of cellular growth [ 143 , 144 ]. However, in contrast with the previous reports, although triple-negative BC (TNBC) is considered one of the most aggressive ones among the molecular subtypes of BC [ 145 , 146 ], Gupta et al [ 147 ] unexpectedly found that MMTVels were present in only 7% of TNBC samples from a Croatian cohort, and similar findings (4%) came from a Brazilian TNBC cohort [ 148 ].…”

Epstein–Barr Virus Association with Breast Cancer: Evidence and Perspectives

“…Considering the relevance of lytic activation in EBV-driven carcinogenesis [ 107 ], these issues lead us to speculate about the possibility of cooperation between EBV and pesticides for BC development. In addition, frequent viral coinfection has been detected in BCs including EBV, HPV and MMTV, suggesting the possibility of interactions among viral pathogens [ 108 ]. Finally, considering all these findings, a hypothetical model is suggested for EBV-mediated breast carcinogenesis, even though additional studies are necessary to solve this conundrum ( Figure 3 ).…”