Abstract
Women with human papilloma virus (HPV)-associated cervical neoplasia have a higher risk of developing breast cancer than the general female population. The purpose of this study was to (i) identify high-risk HPVs in cervical neoplasia and subsequent HPV positive breast cancers which developed in the same patients and (ii) determine if these HPVs were biologically active. A range of polymerase chain reaction and immunohistochemical techniques were used to conduct a retrospective cohort study of cervical precancers and subsequent breast cancers in the same patients. The same high-risk HPV types were identified in both the cervical and breast specimens in 13 (46%) of 28 patients. HPV type 18 was the most prevalent. HPVs appeared to be biologically active as demonstrated by the expression of HPV E7 proteins and the presence of HPV-associated koilocytes. The average age of these patients diagnosed with breast cancer following prior cervical precancer was 51 years, as compared to 60 years for all women with breast cancer (p for difference = 0.001). These findings indicate that high-risk HPVs can be associated with cervical neoplasia and subsequent young age breast cancer. However, these associations are unusual and are a very small proportion of breast cancers. These outcomes confirm and extend the observations of two similar previous studies and offer one explanation for the increased prevalence of serious invasive breast cancer among young women.
Highlights
Women with squamous or glandular precancer of the cervix have a significantly higher risk of subsequent breast cancer than the general female population – odds ratios 1.10 and 1.52, respectively [1]
human papilloma virus (HPV) and Young Age Breast Cancer patients, there is no increased prevalence of breast cancer, which is in contrast to the twofold to sixfold increased prevalence of HPV-associated cervical cancer in these patients [4], and (ii) the HPV viral load in breast cancer is extremely low [5, 6]
We have shown that (i) high-risk HPVs are present in 70% of breast cancers among women who had prior HPV positive cervical neoplasia – HPV types were identical in both prior cervical neoplasia and later breast cancer in 46% of the patients, (ii) HPV E7 was expressed in 64% of invasive breast cancers, and (iii) HPV-associated koilocytes were identified in 32% of breast cancers which is an additional indicator of HPV biological activity
Summary
Women with squamous or glandular precancer of the cervix have a significantly higher risk of subsequent breast cancer than the general female population – odds ratios 1.10 and 1.52, respectively [1]. Women with human papilloma virus (HPV)-associated cervical neoplasia may some years later develop HPV-associated breast cancer [2, 3]. These data indicate that HPVs may have a possible role in some breast cancers, it is unlikely that HPVs have a major causal role. Data from The Cancer Genome Atlas (TCGA), published on line by the Larsson Lab [6], indicate a low prevalence of high cancer risk HPVs in breast cancer. It has been shown that approximately 1.3% of these data are contaminated by HPV 18 (7, Cantalupo, 2015, personal communication)
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