Human Papilloma Viruses and Breast Cancer

Abstract

PurposeHuman papillomaviruses (HPV) may have a role in some breast cancers. The purpose of this study is to fill important gaps in the evidence. These gaps are: (i) confirmation of the presence of high risk for cancer HPVs in breast cancers, (ii) evidence of HPV infections in benign breast tissues prior to the development of HPV-positive breast cancer in the same patients, (iii) evidence that HPVs are biologically active and not harmless passengers in breast cancer.MethodsRNA-seq data from The Cancer Genome Atlas (TCGA) was used to identify HPV RNA sequences in breast cancers. We also conducted a retrospective cohort study based on polymerase chain reaction (PCR) analyses to identify HPVs in archival specimens from Australian women with benign breast biopsies who later developed breast cancer. To assess whether HPVs in breast cancer were biologically active, the expression of the oncogenic protein HPV E7 was assessed by immunohistochemistry (IHC).ResultsThirty (3.5%) low-risk and 20 (2.3%) high-risk HPV types were identified in 855 breast cancers from the TCGA database. The high risk types were HPV 18 (48%), HPV 113 (24%), HPV 16 (10%), HPV 52 (10%). Data from the PCR cohort study indicated that HPV type 18 was the most common type identified in breast cancer specimens (55% of 40 breast cancer specimens) followed by HPV 16 (13%). The same HPV type was identified in both the benign and subsequent breast cancer in 15 patients. HPV E7 proteins were identified in 72% of benign breast specimens and 59% of invasive breast cancer specimens.ConclusionThere were four observations of particular interest: (i) confirmation by both NGS and PCR of the presence of high-risk HPV gene sequences in breast cancers, (ii) a correlation between high-risk HPV in benign breast specimens and subsequent HPV-positive breast cancer in the same patient, (iii) HPVs in breast cancer are likely to be biologically active (as shown by transcription of HPV DNA to RNA plus the expression of HPV E7 proteins), (iv) HPV oncogenic influences may occur early in the development of breast cancer.

Association of High Risk Human Papillomavirus and Breast cancer: A UK based Study

“…Although we have shown the presence of HR-HPV in benign specimens, we were unable to confirm the expression of the HR-HPV protein in theses samples. While we did not find evidence of viral expression in benign cases which were positive for HPV DNA, others were able to show the expression of HPV oncoprotein in benign samples via immunohistochemistry (IHC) method35. The most reasonable conclusion to draw from this is that that the low level of HPV expression could be detected mainly by IHC where the viral expression can be detected even if only in a few cells.…”

The most important questions in cancer research and clinical oncology

“…Lawson et al [43] observed “the presence of high-risk HPV gene sequences in breast cancers; that HPV oncogenic influences may occur early in the development of breast cancer; that HPVs in breast cancer are likely to be biologically active (as shown by transcription of HPV DNA to RNA plus the expression of HPV E7 proteins), and that there appeared to be a correlation between high-risk HPV in benign breast specimens and subsequent HPV-positive breast cancer in the same patient.” In another study, Subhawong et al [44] showed that basal-like breast carcinomas, which resemble HPV-associated squamous cell carcinomas morphologically, frequently exhibit a similar Rb − /p16 + phenotype. A study from Singapore showed a high prevalence of infection with high-risk HPV in breast cancer patients [45].…”

Associаtіon of Еpstеіn - Bаrr vіrus іnfеctіon wіth Brеаst Cаncеr іn Kіrkuk cіty

“…The most іmportаnt risk factors are viral factors whіch аrе consіdеrеd іnfеctіous аgеnts of humаns аnd lіnkеd to thе іncіdеncе of cаncеr іn thе body. Studіеs hаvе shown thаt thе rаtе of 17-20% of cаsеs of cаncеr іs duе to а vіrаl іnfеctіon [5].Іn 1995, 21% of brеаst cаncеr sаmplеs wеrе tаkеn аnd ЕBV wаs dеtеctеd іn thе sаmplеs аftеr thе dіscovеry, sеvеrаl studіеs wеrе conductеd thаt showеd ЕBV іnϳury іn womеn wіth brеаst cаncеr [6]. Humаn cytomеgаlovіrus (HCMV) аnd Еpstеіn -Bаrr vіrus (ЕBV) could potеntіаlly іnvolvе іn brеаst cаncеr [7].…”