Prognostic Value of KI6 Biomarker to Predict Short Term Prognosis of Low Grade Cervical Intraepithelial Neoplasia in Human Papilloma Virus Negative and Positive Patients

Cervical cancer is the most common gynecologic cancer in developing countries. Although this malignancy is preventable, problems exist with screening this cancer. Numerous studies have researched immunohistochemistry methods, such as the KI-67 biomarker as a proliferation marker, to improve screening for cervical intraepithelial neoplasia as the precancerous phase of cervical cancer. These studies mostly screened cytological samples. In the current study, we sought to analyze the correlation between the KI-67 proliferative biomarker and HPV infection in order to predict short-time prognosis in cervical intraepithelial neoplasia as an alternative or ancillary method to current screening methods. Our assessment was based on histologic samples from a different geographic population. This descriptive cohort prospective study included 40 patients diagnosed with low grade cervical intraepithelial neoplasia based on cervical punch biopsy samples after colposcopy examination. We enrolled patients who referred to the Department of Gynecology- Oncology of an academic hospital of Mashhad University of Medical Sciences from 2016 to 2017. All low grade cervical intraepithelial neoplasia samples were investigated for HR-HPV DNA with the Cobas test and immunostaining for the KI-67 biomarker. After a one-year follow-up, we evaluated the prognosis for all patients based on liquid based cytology and HRHPV test. Data were analyzed by SPSS version 23.0 and the Mann-Whitney U and Fisher's exact tests. A P-value < 0.05 was considered significant. We observed a significant difference between HR-HPV positive and negative tests in KI-67 expression (P<0.001), but there were no significant differences in reactivity level of cervical epithelium (P=0.5) and in KI-67 expressions in metaplastic and non-metaplastic epithelium (P=0.88). After one year, most low grade cervical intraepithelial neoplasia cases in group A that had a low staining KI-67 biomarker had evidence of regression. On the contrary, all cases with high grade KI-67 expression didn’t persist or progressed necessarily. The KI-67 biomarker is recommended as a complementary screening test, but not an alternative for triage of high-risk patients with low grade cervical intraepithelial neoplasia. Patients with low grade cervical intraepithelial neoplasia/HR-HPV positive cervical samples and low staining KI-67 antigen could be offered a less aggressive follow-up protocol.