Is Human Papilloma Virus Associated with Breast Cancer? A Review of the Molecular Evidence

Abstract

Background: Although the association of human papillomavirus (HPV) with many cancers is well established, the involvement of HPV in breast cancer remains controversial. The purpose of this study is to perform a comprehensive review of the results and methods used to demonstrate that HPV markers are present in human breast cancer, and how well these studies fulfil the criteria for proving the viral etiology of a cancer. Study Design: We conducted a search for molecular studies published until November 2016 that relate human breast cancer to HPV. Results: Forty-three original molecular studies were found, some of which compared cases to nonneoplastic controls. Some investigations did not identify HPV in mammary tissue, but others identified it with different frequencies of positivity, varying between 1.2 and 86%. In most case-control studies (21/24 studies), positivity in cases was found to be higher than in controls, but odds ratios and confidence intervals were not reported. Conclusion: The results are controversial. However, they arouse a great interest in the potential participation of HPV in breast carcinogenesis, but rather as an essential cause-effect participant, at least as a co-participant in some cases. The circumstance of HPV positivity in breast cancer can be criticized, but the elements that clearly demonstrate it in a number of cases are also relevant.

Prevalence and Type Distribution of High-Risk Human Papillomavirus (HPV) in Breast Cancer: A Qatar Based Study

“…Long-term virus persistence and the participation of other cofactors are needed to increase the risk of cancer progression [28,29]. In support of this statement, our data may suggest that the detection of HPV infection in normal breast specimens is expected to be an early event at the time of diagnosis, followed by progressive and cumulative changes over the years, similar to cervical carcinogenesis [22].…”

“…HPV infection also causes direct effects through the expression of viral oncoproteins that influence carcinogenic mechanisms and its oncogenic role is well-known in cervical cancer [21]. It has recently been suggested that the HPV oncogenicity in breast tissue could be similar to cervical carcinogenesis, in which viral infection could be an early event, followed by cumulative changes over the chronic viral infection [22].…”

Papillomavirus can be transmitted through the blood and produce infections in blood recipients: Evidence from two animal models

“…HPV was detected in the blood of a subset of sexually naïve children with hemophilia who had received multiple transfusions [1]. HPV sequences are sometimes found in tumours of internal organs such as the stomach, prostate, breast, colon, bladder, esophagus, and lung [3,9,11,45–49]. We asked whether these observations could be due to transmission of the virus through the blood.…”

“…Some of these children were hemophiliacs who had contracted HIV through contaminated transfusions. HPV has been detected in malignant tissues, including those of the head and neck [2], esophagus [3], lung [4], colorectum [5,6], prostate [7,8], breast [9,10] and stomach [11,12]. We asked: (1) Could blood be a non-sexual mode for the transmission of papillomavirus infections?…”

Human papillomavirus (HPV) 16 infection is not detected in rectal carcinoma

“…A strong causal relationship has been demonstrated between HPV and some types of cancers such as cervix uteri, penis, vulva, vagina, anus and oropharynx [4,6]. Controversial results have been obtained regarding the role of HPVs in esophagus [6][7][8], oral cavity [6,9], breast [10][11][12] and lung cancers [13,14]. In cervical lesions the HPV DNA is frequently found integrated into the host genome particularly in high grade cervical intraepithelial neoplasia and invasive cancer cases [15,16].…”