Association of Tumor Necrosis Factora-2anda-8Microsatellite Alleles with Human Papillomavirus and Squamous Intraepithelial Lesions among Women in Brazil

Abstract

Infection with oncogenic human papillomavirus (HPV) is considered to be the major risk factor for cervical cancer. Tumor necrosis factor (TNF) is a pluripotent cytokine that plays an important role in inhibiting the action of microbial agents, and TNF microsatellite polymorphisms have been associated with several diseases, including cancer and viral infections. This study analyzed the associations between TNFa to -e microsatellite polymorphisms and the severity of squamous intraepithelial lesions (SIL), according to the presence of the oncogenic HPV16 and HPV18 types. Samples from 146 HPV-positive women with low-grade SIL (LSIL) and high-grade SIL (HSIL) and samples from 101 healthy women were studied. TNF microsatellite polymorphism typing and HPV detection and typing were performed using PCR-amplified DNA hybridized with sequencespecific primers. Data were analyzed by Fisher's exact test using the GENEPOP software. Significant associations were observed between LSIL and the TNFa-8 allele (4/166; P ‫؍‬ 0.04), as well as between TNFa-2 with HPV18 only (16/44; P ‫؍‬ 0.002) and TNFa-2 with HPV18 coinfection with HPV16 (16/44; P ‫؍‬ 0.001). Patients exhibiting the TNFa-2 allele and harboring HPV18, in the presence or absence of coinfection with HPV16, had an increased risk of HSIL occurrence (13/38; P ‫؍‬ 0.04; 5/10; P ‫؍‬ 0.04) compared to patients with other HPV types. These results suggest that the TNFa-8 allele is associated with increased susceptibility to the occurrence of LSIL and that despite the presence of a high TNF-␣ production allele, the ability of HPV18 to resist the inhibitory effects of TNF-␣ may contribute to the occurrence of infection and consequently to HSIL in women with cervical HPV18 infection.

Concentration levels of IL-10 and TNFαcytokines in patients with human papilloma virus (HPV) DNA+and DNA−cervical lesions

“…Other studies noted that infection with HR or other aggressive genotypes of HPV gave rise to transformed cells that were resistant to TNFα-mediated growth inhibition; this outcome seemed to be due to a decreased expression/loss of the TNFα receptors on the infected cells (Simoes et al, 2005;Govan et al, 2006). In contrast, Song et al (2007) reported that TNFα and IL-10 levels did not correlate with pre-cancerous lesions of the cervix after HPV infection.…”

“…Tumor necrosis factor (TNF)-α, which plays a key role in viral clearance and inflammatory reactions after viral infections and cancer (and as such is considered as proinflammatory cytokine), is secreted by several cell types including macrophages and T-lymphocytes (Simoes et al, 2005). In addition, TNFα has anti-tumor properties and is spontaneously released by HPV-infected cells.…”

“…The immune response is mediated through the release of different mediators, which can influence the synthesis of different immunoregulating cytokine networks (Bais et al, 2007). In an immunocompetent host, immune surveillance mechanisms against HPV infection include the participation of different anti-inflammatory and anti-tumor cytokines that affect the growth of HPV-infected cells and facilitating lesion regression (Simoes et al, 2005). Cytokines play a significant role in the defense against HPV-induced infections; among their activities are the modulations of viral replication and the polarizing of the immune response toward T-helper-1 (T H 1) or -2 (T H 2) cell-type patterns (Govan et al, 2006).…”

Tumor Necrosis Factor Alpha rs1800629 Polymorphism and Risk of Cervical Lesions: A Meta-Analysis

“…A total of 117 potentially individual abstracts were found from the the Pubmed, Embase, Web of Science, and Wanfang databases, but only 24 studies were preliminarily identified and were further assessed for inclusion [13]–[25], [30]–[39] (Figure 1). After reviewing the full-texts of those 25 studies, three studies were excluded for irrelevant studies [36], [37], [39] and two were excluded for studies assessing the other TNF gene polymorphisms [35], [38].…”

New viral vaccines for dermatologic disease

“…43 This may in part be due to the reduction of E-cadherin-mediated interactions between keratinocytes and Langerhans cells. 44 As a result, cytokine production is altered, [46][47][48] and the virus is not cleared by the cell-mediated immune system.…”