Several causes of the variable radiotherapy (RT) efficacy have been studied without convincing results. If the HPV-16 infection has been hypothesized to be a predictor of poor response to RT (Ferdousi et al., 2010, Moreno-Acosta et al., 2017), the real clinical impact of HPV-16 and its prognosis significance is still to be demonstrated. In the recent studies (Zacapala-Gómez et al., 2016), was reported that factor receptor insulin-like growth1 (IGF1R) is over-expressed by effect of E6 AA-a, and E-G350 HPV-16 variants. Previous studies have shown a role for IGF1R in cellular radio-resistance in cervical carcinoma; Moreno-Acosta et al., 2012, found that the over-expression of IGF1R is a predictive marker for patients (HPV16 (+)) undergoing Radiotherapy because overexpression of this receptor confers 28.6 times greater risk of treatment failure. The aim of the present study was to prospectively report the detection of HPV-16 variants, gene expression IGF1R and assess the relationship with treatment response.
Detection of HPV 16 variants of 19 patients by PCR-SSCP and direct sequencing and analysis of IGF1R gene expression by real-time PCR. Of these patients, 15 underwent exclusive radiotherapy and four underwent radiochemotherapy.
Three months after treatment completion, out of the 15 patients receiving exclusive RT, 8 experienced complete responses: 3 with the European T350 variant (E-T350 and IGF1R low expression, 2 with the European G350 variant (E-G350) and IGF1R negative expression), 2 with an undetermined European variant (E-Nd) and IGF1R negative expression), and 1 with an Asian-American variant (AAa) and IGF1R negative expression. The other 7 experienced no complete response: Three patients were diagnosed a partial response (2 E-T350, 1 E- G350, and IGF1R overexpression), 3 had a stable tumor (2 E-G350, 1 E-Nd and IGF1R overexpression) and 1 experienced tumor progression (AAa and IGF1R overexpression).
The presence of E-G350 and non-european (eg. AA) variants and overexpression of IGF1R in the no complete response group could be related with radio-resistance. Larger prospective trials are needed to validate the presence of HPV-16 variants and IGF1R expression as a biomarkers of radioresistance.
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Moreno-Acosta P, Vallard A, Molano M, Huertas A, Gamboa Ó, Cotes M, Romero-Rojas A, Rancoule C, Magné N. HPV-16 variants' impact on uterine cervical cancer response to radiotherapy: A descriptive pilot study. Cancer Radiother. 2017 Mar 18. pii: S1278-3218(17)30041-0. doi: 10.1016/j.canrad.2016.09.018
Moreno-Acosta P, Gamboa O, Sanchez de Gomez M, Diaz GD, Romero A, Balart-Serra J, Conrado Z, Levy A, Chargari C, Magne N.IGF1R Gene Expression as a Predictive Marker of Response to Ionizing Radiation for Patients with Locally Advanced HPV16- positive Cervical Cancer. Anticancer Research. 2012; 32: 4319-4326.