Evaluation of p16 and Ki67 expression in cervical neoplasm and its association with human papillomavirus infection: An observational study

Introduction: Cervical cancer is the fourth-most common cancer among females associated with strong viral etiology. Nearly 99.7% of cases are associated with persistent high-risk human papillomavirus infection (hr-HPV). p16 INK4a , a cyclin-dependent kinase inhibitor, is commonly overexpressed in HPV-associated lesions. However, a subset of HPV-associated cervical intraepithelial neoplasia 2/3 lesions exhibits weak/inconsistent immunoreactivity to p16. Ki67, a marker of cellular proliferation, is valuable in distinguishing ambiguous cases as its expression in the normal epithelium is confined to the basal layer but extends to the basal and parabasal layer in premalignant and malignant lesions. Materials and Methods: A total of 150 cases were received during the study period. These cases were analyzed employing HPV DNA detection and immunohistochemistry for p16 and Ki67. Results: Of the 150 cases, 27.3% were chronic cervicitis, 1.3% were endocervical polyp, 0.7% were low-grade squamous intraepithelial lesion (LSIL), 3.3% were high-grade squamous intraepithelial lesion (HSIL), 64.7% were squamous cell carcinoma (SCC), 2% were adenocarcinoma, and 0.6% were adenosquamous carcinoma. hr-HPV was detected in 70.1% cases of SCC and 100% cases of adenocarcinoma and adenosquamous cell carcinoma. p16 was positive in 60.7% cases of SCC, while Ki67 overexpression (3+) was noted in 76.3% of cases of SCC and in all adenocarcinoma cases. HSIL showed +3 Ki67 index in 3/5 cases and +2 in 2/5 cases. One case of endocervical polyp and LSIL showed +1 proliferation index. Benign lesions were mostly negative for Ki67. Significant correlations were observed between p16, Ki67, and HPV (<0.05). Conclusion: The current study highlights the critical role of p16 and Ki-67 as complementary biomarkers in cervical cancer screening. Their integration into routine diagnostics can enhance precision, reduce variability, and support better risk stratification for early intervention.