Link between chronic inflammation and human papillomavirus-induced carcinogenesis (Review)

Abstract

Inflammation is a defense strategy against invading agents and harmful molecules that is activated immediately following a stimulus, and involves the release of cytokines and chemokines, which activate the innate immune response. These mediators act together to increase blood flow and vascular permeability, facilitating recruitment of effector cells to the site of injury. Following resolution of the injury and removal of the stimulus, inflammation is disabled, but if the stimulus persists, inflammation becomes chronic and is strongly associated with cancer. This is likely to be due to the fact that the inflammation leads to a wound that does not heal, requiring a constant renewal of cells, which increases the risk of neoplastic transformation. Debris from phagocytosis, including the reactive species of oxygen and nitrogen that cause damage to DNA already damaged by the leukotrienes and prostaglandins, has an impact on inflammation and various carcinogenic routes. There is an association between chronic inflammation, persistent infection and cancer, where oncogenic action is mediated by autocrine and paracrine signals, causing changes in somatic cells under the influence of the microbial genome or of epigenetic factors. Among the infectious agents associated with cancer, certain genotypes of human papillomavirus (HPV) stand out. HPV is responsible for virtually all cases of cervical cancer and a lower proportion of cancers of the vagina, vulva, anus, penis and a number of extragenital cancers. In the present review, recent advances in the mechanisms involved in the inflammatory response are presented with their participation in the process of carcinogenesis, emphasizing the role of chronic inflammation in the development of HPV-induced cervical cancer.

Celecoxib promotes degranulation of CD8+ T cells in HPV-induced lesions of K14-HPV16 transgenic mice

“…Cytotoxic T lymphocytes (CTL), differentiated from CD8 + T cells, play an important role in the complex immune response which accompanies HPV-induced carcinogenesis [8,9]. CD8 + T cells are recruited to the lesions microenvironment by chemokines released by stromal and/or innate immune cells on site [10].…”

Association of serum cytokines with oral HPV clearance

“…Previous research suggests that although initial HPV infection does not cause an inflammatory reaction,(38, 39) persisting infection can activate inflammatory pathways, including ones with established roles in cancer promotion. (40) Repeated longitudinal cytokine measurements, or cytokine measurements taken directly from the oropharynx, may show a decrease in TNF-α following HPV clearance, and may help clarify temporal patterns of immune response over the course of oral HPV infection.…”

High Levels of EBV-Encoded RNA 1 (EBER1) Trigger Interferon and Inflammation-Related Genes in Keratinocytes Expressing HPV16 E6/E7

“…Interestingly, we demonstrated that EBV localized in infiltrating leukocytes adjacent to tumor epithelium and we did not observe EBV infection in epithelial cells [6]. Thus, we hypothesized that HPV infection, which induces many inflammatory signals [7], recruits EBV-carrying B lymphocytes to the infected area. The presence of EBV may provide signals causing the modulation of HPV-infected cells or microenvironment and contributing to tumorigenesis.…”