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Human papillomavirus (HPV) genotype distribution varies according to the assessment method and the population targeted. This study aimed to assess HPV infection prevalence in women aged 23 to 82 with abnormal cytology attending King Fahad Medical City (KFMC), Riyadh, Saudi Arabia, using retrospective data collected from January 2021 to December 2022. Cytological distribution included 155 samples of atypical squamous cells of undetermined significance (ASCUS) (n = 83), low-grade squamous intraepithelial lesion (LSIL) (n = 46), high-grade squamous intraepithelial lesion (HSIL) (n = 14), atypical squamous cells cannot exclude high-grade squamous intraepithelial lesion (ASC-H) (n = 10), and squamous cell carcinoma (SCC) (n = 2). All samples were submitted to HPV detection and genotyping using Xpert HPV assay specimens. The most prevalent epithelial abnormalities were ASCUS (53.50%). Positive HPV infection results were observed in 52.9% of the samples. The highest prevalence of HPV genotypes, accounting for 31%, was attributed to the other high-risk genotypes, including 31, 33, 35, 39, 51, 52, 56, 58, 59, 66, and 68, followed by high-risk genotype 16, which counted in 11.60% of cases. Individuals who tested positive for HPV 16 were at a high risk of ASC-H, HSIL, and LSIL. Those testing positive for HPV 18–45 exhibited an elevated risk of LSIL, and those with positive results for other high-risk HPV genotypes were at an increased risk of ASCUS and LSIL, suggesting a low oncogenic potential. The results suggest that the percentage of association between samples with abnormal cervical presentation and negative high-risk HPV diagnosis is noticeably increasing. This underscores the need for effective screening programs and an understanding of the impact of specific HPV genotypes on cervical abnormalities.