Deregulated TNF-Alpha Levels Along with HPV Genotype 16 Infection Are Associated with Pathogenesis of Cervical Neoplasia in Northeast Indian Patients

Abstract

Multiple factors are associated with human papillomavirus (HPV) infection related cervical anomalies and its progression to cervical carcinoma (CaCx), but data vary with respect to the underlying HPV genotype and with population being studied. No data are available regarding the role of immunological imbalance in HPV infected CaCx pathogenesis from Northeast India, which has an ethnically distinct population, and was aimed to be addressed through this study. The study included 76 CaCx cases, 25 cervical intraepithelial neoplasia (CIN) cases, and 50 healthy female controls. HPV screening and genotyping were performed by PCR. Differential expression of tumor necrosis factor alpha (TNF-α) was studied at serum level by enzyme-linked immunosorbent assay and tissue level by immunohistochemistry and messenger RNA (mRNA) level by real-time PCR. The data were correlated with interferon gamma (IFN-γ) and NF-κβp65 levels at protein level, as well as HPV16 E6 and E7 expression at transcript level statistically. HPV infection and HPV16 genotype were predominant in the studied cohort. TNF-α was found to be downregulated at both mRNA and protein levels in CaCx cases compared to controls; and the gradient downregulation correlated with progression of the disease from normal→CIN→CaCx. TNF-α expression correlated with insufficient modulation of both IFN-γ and NF-κβp65. The HPV16 E6 and E7 transcripts were found to be sharply upregulated in CaCx cases strongly inversely correlated with the TNF-α expression. Significant role of TNF-α downregulation associated with insufficient IFN-γ and total NF-κβp65 modulation and the resulting significant upregulation of viral transcripts E6 and E7 are key to the HPV16 infection mediated CaCx pathogenesis in northeast Indian patients.

Persistence of oncogenic and non-oncogenic human papillomavirus is associated with human immunodeficiency virus infection in Kenyan women

“…Cervical cancer is responsible for nearly 300,000 deaths annually worldwide; 90% occur among women living in low- and middle-income countries. 1 – 3 Cervical cancer is the most common malignancy in women living in sub-Saharan Africa. 4 – 6 The incidence and mortality rate (15 and 12 per 100,000 women per year, respectively) of cervical cancer in Kenya far exceed the rates for women living in the United States (4 and 1 per 100,000 women per year, respectively).…”

Diagnostic Value of sIL-2R, TNF-α and PCT for Sepsis Infection in Patients With Closed Abdominal Injury Complicated With Severe Multiple Abdominal Injuries

“…Soluble interleukin 2 receptor (sIL-2R) is a nonspecific indicator produced by lymphocytes under conditions such as malignant tumors and infection, which can reflect diseases related to lymphocyte activation and is also a marker of the activation of the immune system (14). Tumor necrosis factor-a (TNF-a) is a major pro-inflammatory cytokine that plays a key role in antimicrobial and anti-inflammatory responses through mechanisms such as the activation of white blood cells, cell proliferation, differentiation, and apoptosis of lymphocytes (15,16). A large number of cytokines are produced in the process of infection, among which TNF-a plays a powerful immune regulatory role in host immune response (17).…”

Longer duration of anti-retroviral therapy is associated with decreased risk of human papillomaviruses detection in Kenyan women living with HIV

“…Cervical cancer causes nearly 300,000 deaths annually worldwide, 90% of which occur among women living in low-and middle-income countries, including Kenya. [1][2][3][4][5][6][7] Oncogenic types of human papillomaviruses ("high-risk", or HR-HPV) are the causative agents of cervical cancer 8 and persistent detection of HR-HPV is associated with an increased risk of invasive disease. [9][10][11][12][13] Women living with human immunodeficiency virus (HIV) infection have a higher incidence of HR-HPV infection and cervical cancer compared to HIV-negative women.…”