To decipher the role of Immune Regulatory Cells and associated Genetic Variation s in HPV mediated Cervical Cancer

Abstract

Cervical cancer is the fourth most common cancer among women globally, with over newline660,000 new cases and 350,000 deaths estimated in 2022. Nearly all cases are linked to newlinepersistent infection with high-risk human papillomavirus (HPV), predominantly types 16 and newline18. Despite the availability of screening and vaccination programs, the burden remains newlinedisproportionately high in low- and middle-income countries, such as India, where it causes newlineapproximately 77,000 deaths annually. The immune system plays a crucial role in newlinedetermining whether HPV infection is cleared or progresses to cancer, yet the precise newlinemechanisms remain insufficiently understood. newlineThis PhD research investigates the immunological and genetic factors contributing to HPV newlinepersistence and cervical cancer development. It focuses on three key immune regulatory cell newlinetypes: T follicular helper (Tfh) cells, which support B cell-mediated antibody production; T newlineregulatory (Treg) cells, which suppress excessive immune activity; and B regulatory newline(Breg) cells, which produce immunosuppressive cytokines like IL-10. Additionally, in this newlinestudy key immune genes and its SNP responsible for HPV virus clearance were also newlineidentified. Using flow cytometry, immunohistochemistry, real-time PCR, cytokine assays, newlineand genetic analysis, the study compared immune and genetic profiles among healthy newlinecontrols, individuals with cervical dysplasia, and those with cervical cancer.Key findings include: newline HPV prevalence was 67.2% among symptomatic participants, exceeding the national newlineaverage of 60.3%. HPV 16 was most prevalent, followed by grouped types (HPV 31, newline33, 35, 52, 58, 51, 56, 66) and HPV 18. newline Altered immune cell dynamics were observed: elevated Tregs and IL-10+ Bregs, newlineand dysregulated Tfh and CD19+ B cell responses correlated with disease severity. newline Pro-inflammatory cytokines (IL-17, IL-18, IL-6, GM-CSF) were significantly newlineincreased, reflecting an imbalanced immune environment that may contribute to newlinecancer progression. newline Tfh cells showed skewed interactions with B cells, potentia