The role of human papillomavirus in the epithelial breast tumor formation

Introduction. Viral infection is considered an etiological factor for the development of hyperplastic processes in the breast epithelium leading to the formation of benign and malignant tumors. Human papillomavirus (HPV) is suspected to cause breast cancer. The aim of the study was to determine the presence of proteins E6 and L1 in breast tumor tissues in benign and malignant lesions, since they are considered to be highly oncogenic in HPV. Materials and methods. We conducted a retrospective analysis of 608 medical records of patients operated on intraductal papilloma (n=304) and other benign breast tumors to determine their association with subsequent breast cancer development. An immunohistochemical study was carried out to determine the presence of proteins of early E6 HPV types 16 and18; late L1 HPV types 1, 6, 11, 16, 18, and 31; and the proliferation Ki-67 in the tissues of benign and malignant epithelial breast tumors. Results. The patients with a history of intraductal papilloma were found to have a 2.3-fold increased risk of developing breast cancer. The majority of samples with a positive reaction to the E6 protein were detected in the group of tumors with the intraductal papilloma structures; the reaction to L1 protein was observed in approximately equal numbers of samples in all groups of benign tumors. A direct moderate correlation was determined between the parameters of protein synthesis Ki-67 and L1 (R=0.54; p=0.0057) in intraductal papilloma, indicating a productive infection and possible participation of the L1 protein in the epithelial proliferation of benign tumors. In cancer samples and benign proliferation, we determined a weak correlation (R=0.47; p=0.0172) between Ki-67 and E6 and L1 parameters, which is likely to be explained by the absence of productive infection in both benign and malignant tumors of the breast. Conclusion. The study showed possible participation of HPV proteins E6 and L1 in the development of proliferative processes in the breast. A history of intraductal papilloma increases the risk of developing breast cancer. Studying the synthesis of proteins E6 and L1 combined makes it possible to determine the stage of the life cycle of HPV. Pairing these values with the Ki-67 index provides information about possible risks of a benign lesion development into a malignant one.