Background: Cervical cancer ranks as the third most prevalent cancer among women globally, having been the leading cause of cancer-related deaths half a century ago. Low-grade squamous intraepithelial lesions (LSIL) typically advance to normal or benign conditions, with only a small percentage progressing to high-grade squamous intraepithelial lesions (HSIL). HSIL is commonly associated with the development of cervical cancer. Currently, there are no reliable biomarkers for predicting HSIL progression in high-risk populations. Apoptosis plays a crucial role in preventing cancer formation, with cell cycle regulators like P15 and P16 being key in G1 cell cycle arrest and oncogene-triggered apoptosis. Aim: To assess and contrast the expression profiles of the candidate biomarker proteins P15 and P16, and to determine their utility as predictive biomarkers for the advancement of cervical dysplasia. Patients and Methods: This study included 50 cervical biopsy cases. Immunohistochemical staining was performed for P15 and P16. Tissue blocks and clinical data were collected from March 2021 to March 2023 in the Department of Obstetrics and Gynecology at the unit of Cancer Early Detection, and Department of Pathology, and Al-Zahra´a University Hospital. Results: High expression of P15 and P16 in HSIL were higher than that in LSIL and NIL, with statistically significant P value of 0.003 for both markers. A P value of <0.0001 indicated a very strong positive correlation between P15 and P16 expression in all cases examined. Conclusion: As cervical dysplasia degree increases, the expression of P15 and P16 increases. Detecting these two markers in combination has important potential for predicting HSIL. IHC expression of P15 and P16 is associated with the grade of histological dysplasia and malignancy, suggesting their prognostic and predictive value in the treatment of cervical lesions.