Human Papillomavirus (HPV) has been detected in several types of cancers such as cervix, vulva, penis, oral cavity or esophagus. There are controversial reports on the role of HPV in some breast cancer around the world. Since 1992, some studies detected HPV-DNA in human breast cancer (1-38); however some authors had reportes negative results (39-48). Furthermore, the studies are very heterogeneous in terms of the methodology employed.The aim of this study was to explore the presence of HPV-DNA in a case-control study, in a series of samples obtained from breast surgeries at the University General Hospital of Alicante (Spain), estimating the strength of the association between the presence of HPV in benign breast disease and breast cancer.
A case-control study was performed to evaluate the presence of HPV infection in a subset of 250 embedded breast cancer, as cases, and 250 embedded benign breast diseases, as controls. The estimated exposure rate (presence of HPV) was 25%in the cases, and 14% in the controls, with a confidence level of 95% and a statistical power of 85% in detecting OR >2.The search for viral DNA was carried out at the Instituto de Estudios Celulares y Moleculares (Spain). Sections measuring 10 µm in thickness were obtained from the tumor area of the paraffin block for the identification of viral DNA. The samples were subjected to three different HPV detection and genotyping methods:GP5+/GP6+ consensus primers, CLART® HPV2 amplification kit (Genomica) and HPV Direct Flow CHIP kit (Master Diagnostica).
The final study included 437 samples: 251 cases (57.4%) and 186 controls (42.6%). The data obtained for determining the presence of HPV in breast cancer tissue samples and establishing the comparisons with the samples corresponding to benign breast tissue, were analyzed using the Chi-squared test. In this regard, the HPV exposure rate among the cases was significantly higher (51.8%) than the HPV exposure rate in the controls (26.3%) (p<0.001). The raw odds ratio was 3.0 (CI 95%: 2.0-4.5). On applying the binary logistic regression model to control for confounding variables, the OR assigned to HPV was seen to be 4.034 (CI 95%: 2.213‑7.352), which means a higher risk of suffering cancer in the presence of HPV, taking into account patient age and breastfeeding. HPV-16 was the most frequent.
HPV is present in a subset of breast carcinomas and therefore, potentially pathogenic related. Moreover, taking in consideration age and breastfeeding, reinforce the influence of HPV-positivity in determining whether a given patient belongs to the case or control group. Nevertheless, further research is necessary to confirm our results.
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