Cervical cancer mortality is high in Texas, especially among Hispanic women living in south Texas and adjacent Mexico. Though human papillomavirus (HPV) infection has a causal role in the development of cervical cancer, there are no published data on the prevalence of HPV genotypes in this underscreened region. We studied 398 Hispanic women on both sides of the border along the lower Rio Grande River to determine the prevalence of HPV genotypes and risk factors for cervical cancer. Using a nested PCR system HPV was detected in 62% of cervical specimens, including all the known high-risk HPV genotypes, with HPV16 and HPV18 the most frequent (30.6% and 23.0%, respectively). Multiple infections were common (29.4% of the infected specimens), and where this occurred we were more likely to find high-risk HPV genotypes. We examined host p53 codon 72 genotype frequencies and found that patients with cervical abnormalities and women with HPV16 and HPV18 infections had a lower genotype frequency of the homozygous (AA) previously reported to be associated with cervical cancer, than uninfected women with no abnormalities. In this US/Mexico border population high rates of potentially oncogenic HPV viruses and multiple infections are consistent with observed elevated cervical cancer rates. These data are further evidence that in this underserved population HPV infections are associated with high rates of malignancy, but that host p53 genotypic variations are unlikely to be primary factors in oncogenesis.