Papilloma virus and breast cancer

Barnes, Jyotsna Batra, Matthias W. Bogdanova, Stig E. Bojesen, Manjeet K. Brenton, Mark N. Caligo, Ian Campbell, Peter T. Carvalho, Andrew T. Chanock, Chu Chen, David C. Christiani, Kathleen B. Couch, Angela Cox, Julie M. Duell, Alison M. Dunning, Miriam Dwek, Diana M. Eccles, Christopher K. Gareth Evans, Peter A. Fasching, Robert L. Ferris, Triantafillos Liloglou, Jane C. Gallinger, Patricia A. Gayther, Graham G.

Giles, Andrew K. Godwin, Mark S. Goldberg, David E. Goldgar, Ellen L. Goode, Marc T. Hamdy, Robert J. Hopper, Richard Houlston, Peter J. Hulick, David J. Hunter, David G. Huntsman, Gregory Idos, Evgeny N.

John, Amit D. Joshi, Radka Kaneva, Beth Y. Karlan, Linda E. Kibel, Lambertus A. Kiemeney, Jeri Kim, Susanne K. Kjaer, Julia A. Levine, Li Li, Christopher I. Li, Annika Lindblom, Noralane M. Milne, Robert J. Nathanson, David E. Neal, Andrew R. Ness, Susan L. Neuhausen, Heli Nevanlinna, Polly A. Newcomb, Lisa F. Nordestgaard, Robert L. Olopade, Andrew F. Park, Nora Pashayan, Michael T. Invasive cancers grow out into and beyond surrounding healthy tissue.

Most breast cancers are invasive. This organization also reports that in , approximately , new diagnoses of invasive and 63, diagnoses of noninvasive breast cancer are estimated to occur in U. Although researchers have connected HPV to cervical cancer, suggesting a link exists between breast cancer and HPV is controversial.

In one study , researchers used 28 breast cancer specimens and 28 noncancerous breast cancer specimens to see if high-risk HPV was in the cells. Results showed high-risk HPV gene sequences in two of the cell lines. In a study , both cancerous and benign breast tissue samples were analyzed. Researchers were able to detect high-risk HPV DNA sequences and proteins in some malignant breast cancer tissue samples. However, they also found evidence of high-risk HPV in some of the benign samples as well.

They theorize that there may be a possibility that breast cancer may eventually develop in these people, but note that further investigation and follow-ups are required to either confirm or disprove this. Taken together with the study, this underlines the importance of continuing to investigate a possible link between breast cancer and HPV. More research is necessary.

No one knows exactly why breast cancer occurs. It may also have genetic causes. These infected cells can then develop mutations, which can cause cancer. However, most of the time papillomas do not require routine follow-ups. Multiple Papillomas and Papillomatosis Multiple breast papillomas present a greater risk and more difficult management problem.

Here the tumors occur deeper within the breast and probably will not cause nipple discharges. Multiple papillomas are more suspicious for subsequent breast cancer development than solitary papillomas.

This is a more serious, higher-risk diagnosis. In this case, regular screening and treatment are necessary. Usual hyperplasia simply means an increase in the number of cells. Whereas in atypical ductal hyperplasia there is an increase in the number of cells that do not appear normal under the microscope. Juvenile papillomatosis tends to have many features of atypical hyperplasia and also some cyst development. Although juvenile papillomatosis is not breast cancer, there is an increase in the risk of breast cancer development, especially if it is bilateral.

Family history also tends to play a role in an increase for risk or tendency of papillomatosis to develop into breast cancer. There is even some evidence to suggest that female relatives of a young person with papilloma, might be more susceptible to breast cancer development than the average population.

However, nobody knows exactly why this is so. Any kind of proliferative cell growth in the breast raises concerns of breast cancer or an increase in the risk for future breast cancer development. Fibrocystic changes of any sort are thought to confer a slightly increased risk of breast cancer development over the long term, but only slightly higher than for the general population. Specialists consider a solitary papilloma to be benign.

Indeed, the risk for breast cancer only slightly increases for women who show any benign fibro-cystic changes. Multiple papillomas, however, are associated with an increase in the risk for breast cancer development, but this is still very low. False positives indicated that the DNA was self-priming and were unsuitable for in situ work this is probably because of fragmented DNA, caused by formalin fixation, acting as primers. The methods used are outlined below. The products were sequenced and the identity of the sequences was determined using the BLAST alignment system.

Previously described protocols were used to extract genomic DNA from the breast cancer specimens Dawkins et al , The amplified products were visualised on a 1. The PCR was independently repeated for each sample. The presence of koilocytosis in the fixed breast cancer series was assessed by light microscopy with koilocyte positive cervical cancer specimens used for comparison. Koilocytes were best characterised by Koss and Durfee, the presence of large cells with relatively small, but irregular and hyperchromatic nuclei surrounded by clear and transparent cytoplasm.

Koilocytosis is restricted to the replicating basal cells and multinucleation is common in these cells. The histological features of HPV positive breast tumours are similar to cervical koilocytosis and have previously been reported by de Villiers et al Polymerase chain reaction PCR product nucleotide sequences of human papilloma virus HPV -positive patient samples and breast cancer cell lines.

There is no sequence variation in specimen 7 when matched against HPV-type 16 genome accession FJ Lanes 1—7 are patient samples breast cancer specimens 1—7.

Lanes 9—11 are negative controls water in place of DNA in reaction. Both samples in lanes 1 specimen 1 and 3 specimen 3 are negative for HPV. Having established the method and demonstrated the presence of HPV in breast cancer cell lines, we screened a series of fixed breast cancer and normal breast tissue specimens using in situ PCR.

As discussed in Materials and Methods section, we eliminated those samples, which potentially could give false-positive HPV results, identified by positive in situ PCR without primers. An unknown number of these eliminated specimens would have been true positives. Accordingly, the data cannot be used to make estimates of prevalence of the presence of these viruses.

Unexpectedly, we saw HPV containing cells in the surrounding normal tissue of some samples Figure 4D. The presence of HPV in normal breast tissues is consistent with the requirement for HPV infection in the breast tissue before HPV-induced tumourigenic transformation of a single clone. Human papilloma virus HPV in cancer cells of ductal carcinoma in situ breast cancer demonstrated by in situ polymerase chain reaction PCR same specimen in all panels.

The appearance of koilocytes in the HPV containing cells shown in panel F selected koilocytes shown by arrows is indicated by the clearing of the cytoplasm and condensed, hyperchromatic nuclei. Seven breast cancer specimens and three normal specimens showed false-positive outcomes when the PCR primer was omitted from the in situ PCR analysis.

These specimens were not considered further. The outcome was confirmed in all the three HPV-positive normal breast specimens. The outcome was confirmed in five of the eight HPV-positive breast cancer specimens.

Minor sequence variations indicate that contamination was unlikely. The identification of two HPV types is a further indication that contamination is unlikely. All controls gave the expected outcomes.

Koilocyte-like cells were also observed in some HPV-positive normal breast tissue specimens. These features are very similar to koilocytosis present in HPV-positive cervical cancer. In this report, we have confirmed the presence of HPV in the nuclei of cells in breast cancer tissue.

The use of in situ PCR localises the HPV to the nuclei of cells within the cancerous tissue, and substantially decreases the possibility that detection of HPV in breast cancer is a contamination.

Given such a high proportion of studies reporting HPV in breast cancer and breast tissue, the question is why some 2 of 17 studies report that HPV is not present in breast cancer. Potential explanations include difficulties in detection due to low viral load and low frequency of HPV in breast cancers in some populations.

The in situ PCR results demonstrate just how much non-cancerous tissue is present in breast cancer specimens, which may explain the difficulty in detection of HPV by standard PCR upon DNA extraction from the whole tissue sample.