Human Papillomavirus In Breast Cancer Research Articles

Abstract P2-26-04: Human papillomavirus protein E6 regulates Toll like receptor-9 expression in breast cancer cells

Abstract Toll like receptor-9 (TLR9) is an innate immunity DNA-receptor, which is widely expressed in various cancers, including breast cancer. Low TLR9 expression in cancer cells was initially associated with poor prognosis among patients with triple negative breast cancer. We have now discovered a similar association also among among other breast cancer subtypes. The mechanism for TLR9-associated poor prognosis is not currently known, but our ongoing studies suggest that it may be due to poor chemotherapy responses. Regulation of TLR9 expression in breast cancer is poorly understood. It has been demonstrated that in cervical cancers, TLR9 expression is suppressed by human papillomavirus (HPV) infections. Although breast cancer is not typically considered HPV-associated, there are reports of HPV in breast cancer. The aim here was to test the hypothesis, that HPV-infections suppress TLR9 expression also in breast cancer. To study this, human breast cancer cells were infected with HPV16 E6-oncoprotein, followed by measurement of TLR9 mRNA and protein in vitro. We also aimed to compare the presence of HPV DNA with TLR9 protein expression in clinical breast cancer specimens. We further studied E6-infection effects on breast cancer proliferation, migration, and invasion. E6-infection decreased TLR9 protein expression in TNBC but not in estrogen receptor expressing (ER+) cells. E6-overexpression significantly altered breast cancer proliferation, but the impact was opposite in TNBC and ER+ cells. No effect on migration and invasion was observed. E6-transfected breast cancer cells were significantly less sensitive in vitro to chemotherapies typically used for the treatment of breast cancer in the adjuvant setting. In vivo studies are pending. HPV DNA was not detected in a pilot cohort of clinical breast cancer specimens (n=37) among Northern Finnish breast cancer specimens. These results indicate that HPV may affect breast cancer TLR9 expression and thereby breast cancer prognosis, through treatment responses. Although HPV was not detected in the small pilot set of our clinical samples, this issue needs to be further studied in larger data sets. Citation Format: Essi Parviainen, Sini Nurmenniemi, Sara Bravaccini, Francesca Pirini, Sara Ravaioli, Arja Jukkola, Katri S. Selander. Human papillomavirus protein E6 regulates Toll like receptor-9 expression in breast cancer cells [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-26-04.

Oncogenic human papillomavirus in breast cancer: molecular prevalence in a group of Congolese patients.

BackgroundSince the work of Band et al. in 1990 (Proc. Natl. Acad. Sci. USA 87:463–467), several studies have suggested a possible link between the pathogenesis of breast cancer and viral infection. Infection with oncogenic HPV has been one of the viruses implicated in breast cancer cases worldwide.ObjectiveTo investigate the presence of HPV DNA in archived paraffin-embedded breast cancer cases at the University Hospital of Brazzaville and to assess the association between viral HPV infections and clinicopathological features.MethodsA total of 40 formalin-fixed paraffin-embedded (FFPE) biopsies were retrospectively collected and available information was recorded. HPV detection and genotyping were performed by real-time PCR by GeneXpert technology (Cepheid, Sunnyvale, USA).Results The mean age was 51.1±11.4 years (range 22–75 years; median was 47). Overall, HPV DNA was detected in six (15%) breast carcinoma samples. HPV-16, the most common genotype was identified in 83.7 % of all samples. HPV porting with clinicopathological features showed no significant difference (P>0.05). However, a statistically significant difference was observed between HPV infection and SBR grade (P=0.05).Conclusion Our study described a high prevalence of HPV-HR in breast cancer cases in the Congolese woman. Future type case-control studies are necessary to better describe the potential role of HPV in the occurrence of breast cancer in Congo.

Histopathological study of Human Papillomavirus (HPV) in breast cancer patients

A large number of epidemiological studies have evaluated the association between Human papillomavirus infection and breast carcinoma, but the results have been inconsistent.Numerous types of cytopathic effect are distinct in living cultures, but fixation and staining of the cells is essential to realize appearances of viral infection such as inclusion bodies. Identifying cytopathic effect and using it as a investigative tool needs much practice in observing stained section of numerous cell types. The present study aimed at diagnosing the histological changes in the malignant breast tissue, which caused by the HPV and comparing them with malignant breast tissue caused by other factors in order to find a way to diagnose the virus through the histopathic effect. A total of 100 samples was included in the study, 20 from benign tumor and 80 carcinomas, including different histopathological change. HPV was detected by using the conventional PCR. The breast cancer sections were examined for the expression of the effect of Human papillomavirus. In separate series the results of using formalin-fixed, paraffin -embedded sections were compared. Overall prevalence of HPV in malignant breast tissue was difference, we found that the histopathological characteristics of HPVassociated breast cancer are very different to breast cancercaused by other factors. Specifically, we showed the presence of HPV in breast cancer associates with the adenocarcinoma, The virus caused more activity in the tumor. Tumor is acinar carcinoma with increased cellularty and proliferative, While, in none infected with virus, there is no increased in cellularty or acinar, in some arease there was dilution of ducts.The observations indicate a likely causal role of HPV in causing a different histopathological change than breast cancercaused by other factors, This helps in the diagnosing of the HPV through cytopathic effect.

Low Prevalence of Human Papilloma Virus in Patients with Breast Cancer, Kerman; Iran

Breast cancer is the first of the most important causes of the deaths of women in the world and in Iran. There are various causes and causes of this cancer, one of which has recently been described as a cause of breast cancer, is the human papillomavirus (HPV). The HPV is transmitted through sexual contact and skin lesions. There are more than 100 types of HPV that can influence different parts of the body. Some types of HPV can cause cancer (such as cervical or anal cancer) and others can cause warts (such as genital or plantar warts). To study the risk of HPV infection in Breast Cancer, we managed a Case-Control study in Kerman, southeast of Iran. For this purpose, 98 paraffin blocks of breast cancer and 40 paraffin blocks of fibrocystic as a control were tested for the presence of HPV DNA using Real-Time PCR, and HPV typing was done using INNo-Lippa assay. HPV DNA was detected in 8 out of 98 patients (8.2%), while it was not detected in the control group samples. HPV types 16, 18 were the most common (62.5%) types in positive samples. The prevalence of HPV in patients with breast cancer of Iran is very low and less than other regions of the world, it seems that maybe rout of transmission of HPV in Iran is under control. No one knows exactly why breast cancer occurs. The environment, hormones, Viruses, or your lifestyle could all play a role in the development of breast cancer. Currently, Vaccination is the best way to prevent cancer that’s due to HPV. However, additional studies on the larger group of patients are needed to explain the roles of HPV in Breast cancer.

Presence of human papillomavirus in breast cancer and its association with clinical features.

e13566Background: Breast cancer (BC) is the most common cancer and leading cause of cancer-related deaths. Recent evidence indicates that a substantial proportion of BC may be caused by viral infec...

Study of association and molecular analysis of human papillomavirus in breast cancer of Indian patients: Clinical and prognostic implication.

ObjectivesHuman papillomavirus (HPV) causes tumors primarily Cervical cancer. Recently, inconsistent reports came up in Breast cancer (BC) too. In India, despite treatment 70,218 BC patients die each year. So, we explored the association of HPV, if any, with BC prognosis in Indian pre-therapeutic (PT) and Neo-adjuvant chemotherapy (NACT) patients with subsequent analysis of HPV profile.MethodsHPV prevalence was checked and analysis of physical status, copy number, genome variation, promoter methylation and expression (mRNA and protein) of the prevalent subtype was done.ResultsHigh prevalence of HPV was observed in both PT (64.0%) and NACT (71.0%) cases with significant association with younger (20–45 yrs) PT patients. Interestingly, HPV infection was significantly increased from adjacent normal breast (9.5%, 2/21), fibro adenomas (30%, 3/10) to tumors (64.8%, 203/313) samples. In both PT and NACT cases, HPV16 was the most prevalent subtype (69.0%) followed by HPV18 and HPV33. Survival analysis illustrated hrHPV infected PT patients had worst prognosis. So, detailed analysis of HPV16 profile was done which showed Europian-G350 as the most frequent HPV16 variant along with high rate of integration. Moreover, low copy number and hyper-methylation of P97 early promoter were concordant with low HPV16 E6 and E7 mRNA and protein expression. Notably, four novel variations (KT020838, KT020840, KT020841 and KT020839) in the LCR region and two (KT020836 and KT020837) in the E6 region were identified for the first time along with two novel E6^E7*I (KU199314) and E6^E7*II (KU199315) fusion transcript variants.ConclusionThus, significant association of hrHPV with prognosis of Indian BC patients led to additional investigation of HPV16 profile. Outcomes indicated a plausible role of HPV in Indian BC patients.

Inconclusive role of human papillomavirus infection in breast cancer.

BackgroundEpidemiological studies have examined the association between human papillomavirus (HPV) and breast cancer, but the findings are inconclusive. This study aimed to detect the prevalence of HPV in breast cancer tissue in patients from northeastern China and define the association between HPV and breast cancer using meta-analysis.MethodsPolymerase chain reaction (PCR) was used to test cutaneous or mucosal HPV DNA sequence in 77 breast cancer samples and 77 corresponding adjacent normal tissues. The prevalence of HPV in breast cancer was estimated by pooling data from 38 studies. A meta-analysis of 16 case–control studies was conducted to investigate the association between HPV and breast cancer.ResultsWe did not find HPV DNA sequence in any of the 154 tissue specimens we tested. However, our meta-analysis revealed a HPV prevalence of 30.30 % (95 % confidence interval [CI] = 22.30–38.40 %) among breast cancer cases; most of these involved high-risk HPV types (35.50 %, 95 % CI = 25.00–46.10 %). HPV prevalence in breast cancer varied by geographic region, publication period, and PCR detection method. An increased risk of breast cancer was observed in association with exposure to HPV (odds ratio [OR] = 3.24, 95 % CI = 1.59–6.57), which was influenced by geographic region, HPV DNA source, PCR primer used, and publication period.ConclusionsHPV, especially high-risk HPV types, may be associated with an increased risk of breast cancer, and this association varies dramatically among geographic regions.

Presence of human papillomavirus in breast cancer and its association with prognostic factors.

Breast cancer accounts for 16% of all female cancers worldwide, and in Venezuela, it is the leading cause of death among women. Recently, the presence of high-risk genotypes of human papillomavirus (HPV) has been demonstrated in breast cancer and has been associated with histopathological features of the tumours. In Venezuela, there is no study which determines the association between the presence of HPV in breast cancer and the histopathological features. The aim of this investigation is to evaluate the presence of HPV in the different types of breast cancer, according to their molecular classification, based on the expression of ER, PR, HER2 and Ki67. With this purpose in mind, we assessed the presence of the HPV genome in 24 breast cancer samples diagnosed with infiltrating ductal carcinoma, ductal carcinoma in situ (DCIS) and lobular carcinoma, by the INNO-LIPA genotyping extra kit and the evaluation of the markers ER, PR, HER2, and Ki67 by immunohistochemistry. The viral genome was found in 41.67% of the total number of samples, 51 being the most frequent genotype with 30.77%, followed by types 18 and 33, with 23.08%, respectively. Most tumours were found in the group of luminal A, with a low range of Ki67 expression. The presence of HPV in breast tumours could affect their growth pattern and metastatic power.

The relationship between Human Papillomavirus and Epstein-Barr virus infections with breast cancer of Iranian patients

Background and Aim: As the etiology and progression of breast cancer r emain incompletely understood, novel routes of disease pa thogenesis are important to consider. Some researchers have been found Human papillomavirus (HPV) and Epstein Barr virus (EBV) in breast carcinomas (BCs). Methods: Paraffin-embedded sections from 65 female patients with breast carcinoma and 53 breast tissues from patients with fibrocystic disease as control were selected. After DNA extraction and amplificati on of housekeeping gene (beta-globin), all suitable samples were evaluated for presence of DNA-EBV and DNA-HPV by using PCR (Polymerase Chain Reaction). Results: HPV DNA sequences were detected in 3 of the 53 benign breast tissue samples but none of the breast carcinoma samples was identified. EBV was detected by PCR in 23 of 65 (35.38%) cases of breas t cancer specimens and 11 of 53 (20.75%) control samples (fibroadenoma 7 of 26 (26.92%) and fibrocystic 4 of 27 (14.81%)) . A total of 118 samples from 34 cases (81/28%) were positive. Statistically, crammer indicator analysis for EBV i nfection in tumor samples and normal samples was 0.46 which indicates a significa nt relationship. Conclusion: Our analysis could not confirm a role of HPV in br east cancer but statistically, significant correlation between EBV infection and breast cancer exists. To demonstrate the possible relationship be tween viral load and breast cancer, need for epidemiological, biological and mo lecular mechanisms to clear the virus is involved in the process of carcinogene sis.

Current Resources for Evidence‐Based Practice January/February 2013

Current Resources for Evidence‐Based Practice January/February 2013

58P Detection of Human Papillomavirus and Epstein-Barr Virus in Breast Cancer

ABSTRACT Aim of the study Breast cancer is the most common malignancy diagnosed in the world's populations. Oncogenic viruses such as human papillomavirus have been identified in benign and cancerous breast tissues which are considered as an involving factor in the etiology of breast cancer. An oncogenic role for Epstein-Barr virus (EBV) in B cell lymphoma and nasopharyngeal cancer has been proposed. The relationship between EBV and breast cancer is not known yet. The purpose of this study was investigation of the presence of human papillomavirus (HPV) and EBV in Iranian patients with breast cancer. Materials and methods Paraffin blocks from 64 female patients with breast cancer and 53 non-cancerous breast tissues (Fibrocystic) as a control, were collected from the Imam Khomeini Hospital and Sizdah Abaan. DNA was extracted according to manufacturer's protocol by kit (QIAGEN, Hilden, Germany). Quality of isolated DNA was checked with primers of beta globin gene by PCR. Then, the appropriate samples were selected. All samples, for detection of HPV DNA were amplified for conserved sequences of the GP5 / GP6 by Real-Time PCR. Then, all of them were evaluated for the presence of DNA-EBV by PCR. Results Based on gene amplification of beta globin, two cancerous tissues and one non-cancerous tumor sample were not suitable and excluded. For DNA- HPV, 3 of 52 breast tissues samples (5.76%) were positive but not detected in any samples of breast cancer. For DNA- EBV, 23 of 65 (35.38%) cases of breast cancer specimens and 11 of 53 (20.75%) control samples were positive for virus. Conclusion Our results are not confirming the role of HPV in breast cancer but for EBV our results were similar to other reports in the world, in which a prevalence of EBV between %30 and 50% is suggested in the association of invasive breast cancer and EBV infection. Most epidemiological, biological and molecular studies is necessary to clear mechanisms involved these virus in the process of carcinogenesis. Disclosure All authors have declared no conflicts of interest.

Prevalence of Human Papillomavirus in Breast Cancer: A Systematic Review

We performed a systematic review and meta-analyses to estimate the prevalence of human papillomavirus (HPV) in breast carcinoma and to explore the reasons for the ongoing controversies about this issue. A comprehensive search of the Cochrane Library, MEDLINE, CANCERLIT, LILACS, and EMBASE databases was performed for papers published from January 1990 to January 2011. The medical subject heading terms were searched for the following: breast neoplasm, breast lesions, breast cancer, and HPV or human papillomavirus. Statistical analysis was performed using REVMAN 5.0. Twenty-nine primary studies, including 2211 samples, were analyzed. Overall, HPV prevalence in patients with breast cancer was 23.0% (95% CI, 21.2%-24.8%). The prevalence of HPV ranged from 13.4% (95% CI, 10.2%-16%) in Europe to 42.9% (95% CI, 36.4%-49.4%) in North America and Australia. The prevalence of HPV in controls was 12.9%. Combinations of 9 case-control studies showed that breast cancer was associated with HPV (odds ratio, 5.9; 95% CI, 3.26-10.67). We found a high prevalence of HPV DNA in breast cancer. There is strong evidence to suggest that HPV has an important role in the development of breast cancer.

Human Papillomavirus (HPV) in breast tumors: prevalence in a group of Mexican patients

BackgroundBreast cancer is one of the main health problems in developed countries, occupying first place in mortality in women. It is well-known that there are risk factors associated with breast cancer development. Nonetheless, in 50–80% of cases known risk factors have not been identified, this has generated the attempt to identify new factors related with this neoplasia as viral infections. The aim of this work is investigate the prevalence of HPV DNA in patients with breast lesions at the Instituto Nacional de Cancerologia de Mexico.MethodsFifty-one cases of breast cancer were selected from the files of the institute and compared by age and tumor size with 43 cases of non malignant breast lesions (fibroadenoma, fibrocystic disease and phyllodes tumor). Paraffin embedded specimens were selected, HPV DNA was analyzed by polymerase chain reaction (PCR) and sequenced for different types of HPV in case of positivity for HPV-DNA. Descriptive analysis of clinical and pathological variables was performed and comparisons between positive and negative cases was done.ResultsAll patients were mexican, mean age was 53.3, median age of menarche was 13 and median tumor size 9 cms. Cervicovaginal cytology was performed to all patients, 1 patient (1.9%) of cancer group had HPV and none in the other group, no cases were diagnosed with cervical dysplasia. In the group of carcinomas 36 (70.5%) were negative and 15 (29.4%) were positive to HPV-DNA, 10(66.6%) were positive for HPV 16, 3(20%) for HPV 18, two cases (13.4%) were positive for both. In the group of benign conditions all were negative to HPV-DNA.ConclusionPresence of HPV in breast cancer in our group of cases is high in comparison to other authors; larger numbers of cases need to be analyzed in order to establish the exact role of this virus in the pathogenesis of breast cancer.

Human papilloma virus: Is it a new etiological factor in breast cancer?

9635 Background: Viruses are known to be associated with human malignancies, e.g.,; Epstein-Barr virus, human papilloma virus (HPV) and human T-cell leukemia virus type I. HPV DNA has been found in uterine cervix, anogenital, oral cavity and esophagus tumors. HPV also has been shown to immortalize the breast epithelial cells and increase their proliferation in vitro. We conducted a prospective study to define the role of HPV in breast cancer. Materials and Methods: The malignant and normal breast tissue samples of 30 consecutive breast cancer patients were obtained postoperatively within the 1st hour of operation. All tissue samples were proven to be invasive ductal/lobular carcinoma histopathologically. DNA extracted from all tissues was amplified with the polymerase chain reaction using HPV consensus primer (MY11; 5'GCMCAGGGWCATAAYAATGG-3'; MY9; 5'CGTCCMARRGGAWACTGATC-3') and HPV type specific primers. HPV 11, 16, 18, 33 subtypes were searched in HPV-DNA positive samples. Results: The median age was 53 (range 30–75). Twenty-five samples (83.3%) of tumoral breast tissue expressed HPV-DNA, 13 normal breast tissue samples (43.3%) were positive as well. But there was a significant difference in HPV-DNA positivity between normal and tumoral breast tissue samples (p= 0.003; Fisher's exact test). HPV 18 was detected in 20 of the HPV-DNA positive tumoral tissue (80%) and in 9 of the HPV-DNA positive normal tissue (69.2%) (p=0.689). HPV-33 also was detected in 24 (96 %) of the HPV-DNA positive tumoral tissue and in 12 (92.3 %) of the HPV-DNA positive normal tissue samples (p= 1.000). The distribution of HPV types 18 and 33 between the normal tissue and tumoral tissue was not significantly different. HPV-11 and 16 were not found in any of the HPV-DNA positive samples. Conclusion: HPV DNA was significantly associated with breast tumor tissue compared to normal breast tissue. Our study could not define the specific HPV subtype involved in breast cancer etiology due to the small number of samples and the possible presence of other HPV subtypes which are not analyzed in the present study. Additional studies looking at other HPV subtypes are needed to clarify the etiological role of the HPV in breast cancer. No significant financial relationships to disclose.

Human papilloma virus: Is it a new etiological factor in breast cancer?

9635 Background: Viruses are known to be associated with human malignancies, e.g.,; Epstein-Barr virus, human papilloma virus (HPV) and human T-cell leukemia virus type I. HPV DNA has been found in uterine cervix, anogenital, oral cavity and esophagus tumors. HPV also has been shown to immortalize the breast epithelial cells and increase their proliferation in vitro. We conducted a prospective study to define the role of HPV in breast cancer. Materials and Methods: The malignant and normal breast tissue samples of 30 consecutive breast cancer patients were obtained postoperatively within the 1st hour of operation. All tissue samples were proven to be invasive ductal/lobular carcinoma histopathologically. DNA extracted from all tissues was amplified with the polymerase chain reaction using HPV consensus primer (MY11; 5'GCMCAGGGWCATAAYAATGG-3'; MY9; 5'CGTCCMARRGGAWACTGATC-3') and HPV type specific primers. HPV 11, 16, 18, 33 subtypes were searched in HPV-DNA positive samples. Results: The median age was 53 (range 30–75). Twenty-five samples (83.3%) of tumoral breast tissue expressed HPV-DNA, 13 normal breast tissue samples (43.3%) were positive as well. But there was a significant difference in HPV-DNA positivity between normal and tumoral breast tissue samples (p= 0.003; Fisher's exact test). HPV 18 was detected in 20 of the HPV-DNA positive tumoral tissue (80%) and in 9 of the HPV-DNA positive normal tissue (69.2%) (p=0.689). HPV-33 also was detected in 24 (96 %) of the HPV-DNA positive tumoral tissue and in 12 (92.3 %) of the HPV-DNA positive normal tissue samples (p= 1.000). The distribution of HPV types 18 and 33 between the normal tissue and tumoral tissue was not significantly different. HPV-11 and 16 were not found in any of the HPV-DNA positive samples. Conclusion: HPV DNA was significantly associated with breast tumor tissue compared to normal breast tissue. Our study could not define the specific HPV subtype involved in breast cancer etiology due to the small number of samples and the possible presence of other HPV subtypes which are not analyzed in the present study. Additional studies looking at other HPV subtypes are needed to clarify the etiological role of the HPV in breast cancer. No significant financial relationships to disclose.

Human papillomavirus in breast cancer.

Histological sections from paraffin-embedded breast carcinoma and axillary lymph nodes were examined for the presence of human papillomaviruses by two different techniques: the polymerase chain reaction (PCR) and the in situ hybridization with biotin-labelled probes. By PCR we detected HPV 16 DNA sequences in 29.4% of breast tumours and in some metastatic lymph nodes, though we were unable to identify any HPV DNA sequences by in situ hybridization. These results suggest that HPV's could play a role in the genesis of breast neoplasia.