Reply: Breast cancer, human papilloma virus and sexual activities

Lawson, James S.; Glenn, Wendy K.; Whitaker, Noel J.

doi:10.1038/sj.bjc.6604104

Cited by 5 publications

(7 citation statements)

References 20 publications

(24 reference statements)

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“…Human papilloma virus-positive breast cancer is more common in young when compared with older women, an observation which is compatible with sexual transmission of HPVs among sexually active younger women ( 173 ). HPVs have been identified in peripheral blood which is a possible means by which they are transferred from infected genitals to the breast ( 174 ).…”

Section: High-risk Human Papilloma Viruses and Breast Cancermentioning

confidence: 83%

Oncogenic Viruses and Breast Cancer: Mouse Mammary Tumor Virus (MMTV), Bovine Leukemia Virus (BLV), Human Papilloma Virus (HPV), and Epstein–Barr Virus (EBV)

Salmons²,

2018

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BackgroundAlthough the risk factors for breast cancer are well established, namely female gender, early menarche and late menopause plus the protective influence of early pregnancy, the underlying causes of breast cancer remain unknown. The development of substantial recent evidence indicates that a handful of viruses may have a role in breast cancer. These viruses are mouse mammary tumor virus (MMTV), bovine leukemia virus (BLV), human papilloma viruses (HPVs), and Epstein–Barr virus (EBV-also known as human herpes virus type 4). Each of these viruses has documented oncogenic potential. The aim of this review is to inform the scientific and general community about this recent evidence.The evidenceMMTV and human breast cancer—the evidence is detailed and comprehensive but cannot be regarded as conclusive. BLV and human breast cancer—the evidence is limited. However, in view of the emerging information about BLV in human breast cancer, it is prudent to encourage the elimination of BLV in cattle, particularly in the dairy industry. HPVs and breast cancer—the evidence is substantial but not conclusive. The availability of effective preventive vaccines is a major advantage and their use should be encouraged. EBV and breast cancer—the evidence is also substantial but not conclusive. Currently, there are no practical means of either prevention or treatment. Although there is evidence of genetic predisposition, and cancer in general is a culmination of events, there is no evidence that inherited genetic traits are causal.ConclusionThe influence of oncogenic viruses is currently the major plausible hypothesis for a direct cause of human breast cancer.

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Section: High-risk Human Papilloma Viruses and Breast Cancermentioning

confidence: 83%

Oncogenic Viruses and Breast Cancer: Mouse Mammary Tumor Virus (MMTV), Bovine Leukemia Virus (BLV), Human Papilloma Virus (HPV), and Epstein–Barr Virus (EBV)

Salmons²,

2018

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“…There is substantial evidence which indicates a potential role for high risk HPVs in breast cancer. This evidence includes (i) meta-analyses of 22 studies conducted in a wide range of countries indicate that infection with high risk HPVs is associated with an increased risk of breast cancer with an overall odds ratio of 5.4, there are marked differences between countries in the prevalence of high risk HPVs in breast cancer [ 29 ], (ii) recent studies in the United Kingdom and Spain also indicate an increased risk of breast cancer associated with HPV infection [ 30 , 31 ], the risk differs according to HPV type, with 5.7 fold higher risk for HPV 16, 3.6 fold increase for HPV 33 and 3.0 fold increase for HPV 18 [ 29 ], (iii) HPVs immortalize and transform human mammary epithelial cells [ 32 ], (iii) HPV E6 and E7 oncoproteins have been identified in breast cancers, however, there is a low level of transcription of these oncoproteins which suggests that any influences of HPVs in breast cancer are likely to be indirect [ 4 , 33 ], (iv) high risk HPVs have been identified in the SK-BR-3 breast cancer cell line [ 34 ], (v) HPV type 16 E6 and E7 oncoproteins convert non-invasive and non-metastatic breast cancer cells to invasive and metastatic phenotypes [ 35 ], (vi) HPV-positive breast cancer is more common in young as compared to older women, an observation which is compatible with sexual transmission of HPV among sexually active younger women [ 36 ], (vi) HPV positive koilocytes have been identified in breast cancers [ 37 ], (vii) the prevalence of HPV positive breast cancer is higher in women with prior HPV associated cervical cancer [ 38 ], (viii) high risk HPV gene sequences are present in benign breast tissues prior to the development 3 to 10 years later of same HPV type positive breast cancers [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Multiple oncogenic viruses are present in human breast tissues before development of virus associated breast cancer

Lawson

Glenn

2017

Infect Agents Cancer

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BackgroundMultiple oncogenic viruses including, mouse mammary tumor virus, bovine leukemia virus, human papilloma virus, and Epstein Barr virus, have been identified as separate infectious pathogens in human breast cancer. Here we demonstrate that these four viruses may be present in normal and benign breast tissues 1 to 11 years before the development of same virus breast cancer in the same patients.MethodsWe combined the data we developed during investigations of the individual four oncogenic viruses and breast cancer. Patients who had benign breast biopsies 1–11 years prior to developing breast cancer were identified by pathology reports from a large Australian pathology service (Douglas Hanly Moir Pathology). Archival formalin fixed specimens from these patients were collected. The same archival specimens were used for (i) investigations of mouse mammary tumour virus (also known as human mammary tumour virus) conducted at the Icahn School of Medicine at Mount Sinai, New York and at the University of Pisa, Italy, (ii) bovine leukemia virus conducted at the University of California at Berkeley,(iii) human papilloma virus and Epstein Barr virus conducted at the University of New South Wales, Sydney, Australia.Seventeen normal breast tissues from cosmetic breast surgery conducted on Australian patients were used as controls. These patients were younger than those with benign and later breast cancer.ResultsStandard and in situ polymerase chain reaction (PCR) methods were used to identify the four viruses. The detailed methods are outlined in the separate publications.: mouse mammary tumor virus, human papilloma virus and Epstein Barr virus (Infect Agent Cancer 12:1, 2017, PLoS One 12:e0179367, 2017, Front Oncol 5:277, 2015, PLoS One 7:e48788, 2012).Epstein Barr virus and human papilloma virus were identified in the same breast cancer cells by in situ PCR.Mouse mammary tumour virus was identified in 6 (24%) of 25 benign breast specimens and in 9 (36%) of 25 breast cancer specimens which subsequently developed in the same patients.Bovine leukemia virus was identified in 18 (78%) of 23 benign breast specimens and in 20 (91%) of 22 subsequent breast cancers in the same patients.High risk human papilloma viruses were identified in 13 (72%) of 17 benign breast specimens and in 13 (76%) of 17 subsequent breast cancers in the same patients.Epstein Barr virus was not identified in any benign breast specimens but was identified in 3 (25%) of 12 subsequent breast cancers in the same patients.Mouse mammary tumour virus 3 (18%), bovine leukemia virus 6 (35%), high risk human papilloma virus 3 (18%) and Epstein Barr virus 5 (29%) were identified in 17 normal control breast specimens.ConclusionsThese findings add to the evidence that multiple oncogenic viruses have potential roles in human breast cancer. This is an important observation because evidence of prior infection before the development of disease is a key criterion when assessing causation.

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“…In addition to the epidemiologically based evidence outlined above, there is substantial but incomplete evidence, which indicates a potential role for HPVs in breast cancer. This evidence includes: (i) HPVs immortalize and transform human mammary epithelial cells ( 13 ), (ii) HPVs are located in breast cancer cell nuclei ( 8 ), (iii) HPV E6 oncoprotein has been identified in breast cancers ( 8 ), (iv) high-risk HPVs have been identified in breast cancer cell cultures ( 8 ), (v) HPV-positive breast cancer is more common in young as compared to older women, an observation which is compatible with sexual transmission of HPV among sexually active younger women ( 14 , 15 ), (vi) approximately 16% of normal Australian women are serologically HPV type 16 positive ( 16 ), and (vii) HPV-positive koilocytes have been identified in breast cancers ( 17 ).…”

Section: Introductionmentioning

confidence: 99%

Human Papilloma Viruses and Breast Cancer

et al. 2015

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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.

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Reply: Breast cancer, human papilloma virus and sexual activities

Cited by 5 publications

References 20 publications

Oncogenic Viruses and Breast Cancer: Mouse Mammary Tumor Virus (MMTV), Bovine Leukemia Virus (BLV), Human Papilloma Virus (HPV), and Epstein–Barr Virus (EBV)

Oncogenic Viruses and Breast Cancer: Mouse Mammary Tumor Virus (MMTV), Bovine Leukemia Virus (BLV), Human Papilloma Virus (HPV), and Epstein–Barr Virus (EBV)

Multiple oncogenic viruses are present in human breast tissues before development of virus associated breast cancer

Human Papilloma Viruses and Breast Cancer

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