Basic Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Oncol. Nov 10, 2018; 9(7): 123-132
Published online Nov 10, 2018. doi: 10.5306/wjco.v9.i7.123
Lymphocyte subsets predictive value and possible involvement of human papilloma virus infection on breast cancer molecular subtypes
Andreína Fernandes, Adriana Pesci-Feltri, Isabel García-Fleury, Marco López, Vincent Guida, Marisol De Macedo, María Correnti
Andreína Fernandes, Marisol De Macedo, María Correnti, Oncology and Hematology Institute, Caracas 1050, Venezuela
Adriana Pesci-Feltri, Isabel García-Fleury, Marco López, Vincent Guida, University Hospital of Caracas, Caracas 1050, Venezuela
Author contributions: Fernandes A and Correnti M designed research and wrote the paper; Fernandes A collected data and samples, analyzed and interpreted the data; De Macedo M analyzed the flow cytometry data; Pesci-Feltri A, García-Fleury I, López M, Guida M conducted the mastectomies.
Supported by FONACIT Project, No. G2005000408; and PEII Project, No. 2012001201.
Institutional review board statement: Approved by Bioethics Committee of the University Hospital of Caracas.
Conflict-of-interest statement: The authors confirm that they do not have any conflict of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Andreína Fernandes, PhD, Biologist, Assistant Professor, Oncology and Hematology Institute, University City, Minerva Street, Caracas 1050, Venezuela. andreinafernandesb@gmail.com
Telephone: +58-414-2754878 Fax: +58-212-6053815
Received: May 28, 2018
Peer-review started: May 28, 2018
First decision: July 9, 2018
Revised: August 26, 2018
Accepted: October 24, 2018
Article in press: October 24, 2018
Published online: November 10, 2018
Processing time: 165 Days and 5.1 Hours
ARTICLE HIGHLIGHTS
Research background

Breast cancer is the leading cause of death among women, classified in molecular subtypes according to a genetic profile. Approximately 18% of human cancers are caused by infectious factors, and it is recognized that breast cancer is strongly related to environmental factors, such as viruses, diet, radiation, among others. Human papilloma virus (HPV) has been detected in 0% to 86% of breast cancer tumors, and it represents a possible risk factor. The host immune response might influence the prognosis of cancer patients after standard treatment.

Research motivation

It was recently suggested that HPV presence may act as a risk factor in breast cancer development, but it has not been correlated with molecular subtypes. In addition, it is important to evaluate the immune response of breast cancer patients and to be able to suggest some prognostic values that make it possible to offer better patients treatment.

Research objectives

The main objective is to detect HPV presence and to characterize the cellular immune response in breast cancer patients based on the molecular subtypes.

Research methods

The patients inclusion was done prospectively, and the breast cancer molecular classification was made according to the St. Gallen International Breast Cancer Conference. HPV detection and genotyping were performed using HPV INNO-LIPA Genotyping Extra test, and lymphocyte subsets were measured by flow cytometry.

Research results

Luminal A was the most frequent breast cancer molecular subtype (33.33%), and HPV was detected in 25% of the breast cancer patients, with genotype 18 as the most frequent in the studied population. The means of CD3+, CD4+ and CD8+ subsets were decreased in patients with breast cancer, respective to benign pathology, with a statistically significant difference between CD8+ values (P = 0.048). The mean of NK+ cells was increased in the benign pathology group. HER2+ and Luminal B HER2+ tumors had the lowest counts of cell subsets. The HPV breast cancer patients had elevated counts of cellular subsets.

Research conclusions

It can be observed that HPV positive breast cancer tumors have a better prognosis, correlated with Luminal A subtypes, and show a better cellular immune response, specifically in relation with TCD8+ cells counts, suggesting a better response to chemotherapy and radiant treatment, as in the case of HPV positive oropharynx tumors.

Research perspectives

Future effforts should focus on evaluating patients disease-free survival, based on HPV positivity in the tumor tissue. In addition, viral load and HPV genome integration, the identification of HPV variants by sequencing, and the infiltrating lymphocytes in the tumor bed should also be studied. As a final consideration, the experience of working with fresh samples is complex and involves a process of sample collection in the operating room, in addition to the management of bioethical parameters, and our experience will allow for the possibility of obtaining more accurate results.