Cervical cancer (CxCa) stands as a significant cause of cancer-related deaths among women globally. Specifically, in the Rio Grande Valley (RGV), comprising Cameron, Hidalgo, Willacy, and Starr counties, the highest CxCa mortality in the U.S. has been identified. The initiation of HPV infection represents a pivotal event in the malignant transformation of the cervical zone, established as the primary cause leading from intraepithelial lesions to CxCa. The most prevalent cytopathologic manifestations of cervical HPV infection are low-grade squamous intraepithelial lesions situated in the cervix's transformation zone. The prevalence of HPV infection and its various genotypes differs significantly worldwide. Different populations may harbor distinct HPV genotypes within their genital tracts. Nevertheless, factors such as high poverty rates, poor nutrition, unknown environmental influences, socio-behavioral elements, and limited education along the Mexican border might also significantly contribute to this health disparity. Understanding the disease pathology and devising new approaches to combat it in specific populations necessitates crucial information regarding HPV prevalence, HPV genotypes, and the frequency of HPV 16 E6 genomic variance among women from diverse populations, along with their associations with socio-behavioral factors. However, this vital information, concerning either HPV prevalence or the distribution of HPV types, remains unavailable for RGV women, who are profoundly affected by CxCa. Consequently, we propose investigations to gather this critical information regarding RGV women. We believe this knowledge will be immensely valuable in mitigating the CxCa disparity among this highly underserved population. Our hypothesis posits that analyzing HPV genotype prevalence, frequency of HPV 16 E6 genomic variants, and immunological factors will illuminate the cause of CxCa disparity in RGV women. In aim 1, we will determine the prevalence of HPV infection and identify the specific HPV types of present. This analysis will involve cervical mucosa samples collected from women in rural RGV. Samples from Caucasian women will also be analyzed for comparison. In aim 2, we propose investigating the existence of Ig types (representing the humoral response), cytokines (representing the cellular response), and genetic polymorphisms within immune response genes in cervical mucosa samples. Aim 3, achieved using PDX mouse models of HPV16 E6 variants, is designed to explore the frequency and incidence of different HPV16 E6 genomic variants, investigating their oncogenic, metastatic potential, and role in drug resistance, all contributing to the aggressiveness of the disease and poor therapeutic outcomes of CxCa. The outcomes of this study will be instrumental in developing innovative prevention and therapeutic strategies to alleviate the CxCa disparity among the RGV Hispanic women population.