IGF1R Gene Expression as a Predictive Marker of Response to Ionizing Radiation for Patients with Locally Advanced HPV16-positive Cervical Cancer

Aim: The aim of this study was to evaluate the predictive utility of Insulin-like growth factor-1 receptor (IGF1R), IGF1, IGF2, Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and of hemoglobin levels for tumor response to exclusive radiotherapy, in patients with locally advanced Human papillomavirus (HPV) 16-positive cervical cancer. Patients and Methods: From 102 patients treated at our institutes, 38 patients with histologically-proven HPV16- positive cervical cancer were included in this prospective case-controlled study. All patients underwent exclusive radiotherapy-only. Complete response was defined as an absence of residual disease at clinical examination and radiological imaging, three months after the completion of treatment. Gene expression levels, assessed before radiotherapy, were compared between responders and non- responders. Controls consisted of normal cervical tissue samples from 30 patients with non-oncological indications. Results: Twenty patients (52.6%) showed a complete response. Gene expressions of IGF1R (34%), IGF2 (24%), and GAPDH (median=3.26 versus 2.12) were increased in cancer patients, in comparison with the control group. Higher levels of expression of GAPDH were observed in patients co- expressing IGF2 and IGF1R, who had a hemoglobin level ≤11g/dl (p=0.05). Clinical characteristics in the responder and in the non-responder groups were similar. In bi-variate and multi-variate analyses, IGF1R expression was the only factor predictive of response to radiotherapy (p=0.018). Accordingly, patients with IGF1R expression had a 28.6-fold greater risk of treatment failure. Conclusion: In our study, IGF1R was a strong predictive marker of lack of response to radiotherapy. Larger prospective trials are needed to validate IGF1R as a biomarker of radiation response for patients with HPV16-positive cervical cancer. Cervical cancer of the uterine cervix is the second most common cancer in women worldwide and the fifth leading cause of cancer-related deaths (1). Focusing on Colombia, cervical carcinoma is the first representative cancer and the leading cause of cancer-related death in women of reproductive age (2, 3). Moreover, most cases are diagnosed at advanced stages and infection with high risk human papillomavirus (HPV), mainly HPV16 (57% of cases) and