Background <p>Cervical cancer remains a major public health concern in Ghana, with limited screening coverage and late-stage presentation. Biomarkers such as p16 and p53 have been explored for their diagnostic and prognostic relevance in cervical cancer. The study aims to elucidate the possibility of using p16 immunohistochemistry as a surrogate marker for HPV infection in cervical cancer among other things and role of p53 in cervical cancer.</p> Methods <p>A retrospective descriptive study was conducted on 135 Formalin-Fixed-Paraffin-Embedded archived cervical tissue samples at a tertiary facility in Kumasi, Ghana. Histological evaluation and immunohistochemical staining for p16 and p53 were performed. Data were analysed using SPSS with associations between biomarker expression and clinicopathological variables (age, histological type, tumour grade) assessed.</p> Results <p>The age range of the participants was 31–115 year with a mean age of 58.93 ± 17.88 years. Most cases (96.3%) were squamous cell carcinoma, with 49.6% being poorly differentiated. p16 was positively expressed in 71.11% of cases, while p53 showed 63.70% positivity. Significant associations were observed between p16 and tumour grade (<i>p</i> = 0.02), and between p53 and histological type (<i>p</i> = 0.021). No significant correlations were found between marker expression and age (<i>p</i> = 0.174).</p> Conclusion <p>The high expression of p16 and p53, particularly in squamous and high-grade lesions, shows their potential role in early detection and prognostication of cervical cancer. These biomarkers may serve as cost-effective tools in resource-limited settings like Ghana, supporting improved clinical decision-making.</p>