High Expression of Vascular Endothelial Growth Factor, Ki-67, and Protein 53 are Risk Factors for Poor Response of Paclitaxel-Carboplatin Neoadjuvant Chemotherapy in Stadium IB3, IIA2, and IIB Cervical Cancer

Background: The therapeutic strategy for stage IB3, IIA2, and IIB cervical cancer is still controversial. The modalities are chemoradiation, radical hysterectomy surgery, or administration of neoadjuvant chemotherapy followed by radical hysterectomy. Response to chemotherapy is determined by tumor vascularization or angiogenesis, proliferative activity, and genetic instability of cervical cancer. The marker of tumor cell proliferation is the Ki-67 protein. In cervical cancer, the p53 gene is suppressed by human papillomavirus (HPV). The HPV E6 protein promotes the degradation of p53 thereby inhibiting stabilization and activation of p53. This study aimed to prove that high expression of VEGF, Ki-67, and p53 are risk factors for a poor response to neoadjuvant chemotherapy. Methods: This was a case-control study that was conducted at the Department of Obstetrics and Gynecology in one tertiary hospital in Denpasar from October 2021 to April 2022. There were 56 samples included in this study, which were divided into two equal groups, namely good response and poor response to neoadjuvant chemotherapy. Data were analyzed using the software SPSS-24 including the Kolmogorov-Smirnov normality test, Chi-square, and multiple regression logistics. Data were presented in tables and described narratively. Results: It was found that the risk of a poor response to chemotherapy on the expression of VEGF VEGF, Ki-67, and p53 were 11.5, 15.0, and 8.33 times, respectively. We obtained a formula for calculating chemotherapy response, y = -7.3+ 1.6 VEGF + 1.6 Ki-67 + 1.8 p53. High VEGF, Ki-67, and p53 expressions were scored 1, and low expressions were scored 2. The limit value used is 0.05. The result y < 0.05 means the risk of poor response to chemotherapy and the value of y > 0.05 means good response. Conclusion: This formulation can be used as a parameter to assess the risk of poor response to neoadjuvant chemotherapy in stage IB3, IIA2, and IIB cervical cancer which can be applied in clinical practice in the treatment of cervical cancer.