Background: Following breast cancer, cervical carcinoma is the second most common malignancy among Indian women, with a mortality rate of 18.7.The incidence of cervical cancer is 18.3, which is notably higher than worldwide. Regular screening for cervical cancer will significantly reduce both mortality and morbidity rates. Aim and objectives: To study the correlation between p16 and Ki-67 immunohistochemistry biomarkers and the histopathological diagnosis of preinvasive lesions of the cervix. Materials and methods: A prospective study was conducted in the department of obstetrics and gynaecology at a tertiary care center, Puducherry, from 2021 to 2023. Women visiting the gynecology OPD (age-group 25�45 years) underwent visual inspection with acetic acid (VIA). Women with acetowhite lesions were enrolled (100 cases), and biopsies taken from these lesions were sent for histopathological examination and immunohistochemistry staining of biomarkers p16 and Ki-67. Results: Out of 15 cervical intraepithelial neoplasia (CIN) I cases, five cases (33.3) were positive for both p16 and Ki-67. Of the eight cases of CIN II, dual positivity was seen in 75, and all CIN III and squamous cell carcinoma showed dual positivity (100). Human papillomavirus (HPV) DNA was positive in all dual positivity cases. Conclusion: This study concludes that preinvasive lesions of the cervix and their severity are associated with the expression of both p16 and Ki-67. Therefore, these biomarkers can be utilized for the early diagnosis of preinvasive cervical lesions which are likely to progress, enabling timely intervention and reducing the prevalence of cervical carcinoma. Clinical significance: The significance of p16 and Ki-67 in cervical biopsies lies in their specificity for high-risk HPV (HR-HPV) associated preinvasive lesions, which are likely to progress further to high-grade lesions due to persistent and prolonged HPV infection. Early diagnosis of preinvasive lesions of the cervix helps in early intervention and can reduce the progression to cervical carcinoma. © 2025 Elsevier B.V., All rights reserved.