TIPOS CELULARES ENVOLVIDOS NA RESPOSTA IMUNE À INFECÇÃO DA CÉRVICE UTERINA POR PAPILOMAVÍRUS DE ALTO RISCO ONCOGÊNICO (HR-HPV)

Abstract

The relationship between HPV and the immune response cells is important to comprehend the pathophysiology of the infection and its role in neoplastic progression. It is known that high-risk human papilomavírus (HR-HPV) is the main reason which leads to cervical cancer, thus the association among immune response cells, the virus, and its behavior according to cervical disease development, could provide new ways to patients follow up and a better understanding of the entire process. This work aims to identify the immune response cells involved in the high-grade intraepithelial lesion (HSIL) and cervical cancer development, related to uterine cervix infection caused by HR-HPV. A systematic review study was carried out to answer such a question. Cross-sectional, cohort, and case-control studies were included in the study. The study population are women who have direct and indirect positive tests for HPV. The total amount of primary studies identified was 6698 and after the duplicate’s exclusion, a total of 6040 studies remained. Subsequently, 5957 studies were excluded since they were not related to our question. Hence, 83 studies were available to be evaluated as a complete text. As an extra step, manual inclusion of studies was done. At this point, once again 2 reviewers executed the process of search and reading the selected studies, and the questions left were solved by a third person. Afterward, the final number of studies included in this review was 38 as the others were not eligible to answer our question directly. They were 10 from indirect methodology and 28 from direct. The cervical lesions were distributed according to the severity in High grade squamous intraepithelial lesion (HSIL), Low grade squamous intraepithelial lesions (LSIL) and Negative for intraepithelial lesion or malignancy (NILM). The cellular types presented by the publications were T lymphocytes (LT), B lymphocytes (LB), regulatory T lymphocytes (LTregs), macrophages, natural killer cells (NK), natural killer T cells (NKT), Langerhans cells (LC), and dendritic cells (DC). Among all the relationships observed between the cells of the immune response and the viral infection/lesions according to the direct and indirect methodology, the presence of LT, LTregs, and Macrophages can be highlighted as the main ones. These cells were increased in a greater number of studies associated with patients with HR-HPV infection and/or high-grade cervical lesions, as well as, in agreement with each other, in the vast majority of findings in both methodologies. The risk of bias of the publications included, as well as the relationship between the quality of the evidence, were verified using the New Castle Ottawa and GRADEpro scale, respectively. The present work, through the identification of immune response cells in women with HR-HPV infection, contributes suggestively to the establishment of strategies for monitoring the progression or remission of cervical lesions as well as an initial proposal for new more focused studies regarding the importance and functions effectors of such cells. However, it is necessary to consider the importance of further longitudinal studies for a better understanding of the long-term immune response as well as the absence of inclusion and exclusion factors in most of the included studies. The results found provide us with preliminary data suggestive of the importance of LT, Tregs, and Macrophages in future research, given the agreement between the findings of cell populations and their relationship to HR-HPV and cervical lesions.