Comparative Clinicopathological Features and p16 Expression in Squamous Cell Carcinoma and Adenocarcinoma of the Cervix: A Single-Center Retrospective Cohort Study in Saudi Arabia (2020–2024)

<b>Background</b>: Cervical cancer remains a major global health burden, with squamous cell carcinoma (SCC) and adenocarcinoma (ADC) representing the two predominant histological subtypes. Comparative clinicopathological patterns between SCC and ADC in contemporary cohorts remain of interest, but inference is often limited by small single-center datasets. <b>Methods</b>: We conducted a retrospective single-center cohort analysis of cervical cancer patients treated between 2020 and 2024. Demographic, clinical, and pathological variables, including p16 immunohistochemistry, histological subtype, differentiation grade, FIGO stage, and survival status, were analyzed. Comparative analyses were performed using appropriate exact tests, and survival was assessed using Kaplan-Meier methods. <b>Results</b>: The cohort included 85 patients: 69 with squamous cell carcinoma and 16 with adenocarcinoma. Both subtypes demonstrated similarly high p16 positive rates (89.9% vs. 93.8%, <i>p</i> = 1.00). Menopausal status emerged as a distinguishing factor (<i>p</i> = 0.0047), with SCC patients more likely to be postmenopausal. SCC patients were older on average (52.16 vs. 48.2 years: <i>p</i> = 0.0131). Analyses involving p16 status were interpreted descriptively due to the very small number of p16-negative cases. Kaplan-Meier analysis revealed significant survival differences by clinical stage (log-rank <i>p</i> = 0.03), with high-stage patients showing progressive decline from 95% to 73% survival over five years, while low-stage patients maintained 100% survival. <b>Conclusions</b>: In this retrospective single-center cohort, SCC and ADC showed similar p16 positivity rates and clinical stage remained the most informative prognostic variable. Apparent subtype-related demographic differences and multivariable associations should be considered hypothesis-generating rather than definitive. Larger multicenter studies with standardized pathology and p16 assessment, direct HPV testing/genotyping, and more complete clinical and prevention-related data are needed before prognostic or clinical conclusions are drawn.