Background/Aim: This study aimed to describe genomic alterations on squamous cell cervical and anal carcinomas. Materials and Methods: From 2013 to 2019, 3,269 patients were included in the molecular screening ProfiLER trial. Only patients with non-metastatic cervical or anal cancer, and those initially treated with radiotherapy in a curative intent were selected. Genetic analyses were performed by next generation sequencing (NGS). Results: Genomic alterations were observed in most patients: 5 patients out of 15 (33.3%) had at least one mutation on NGS and 4 out of 15 (26.7%) had at least one aberration of the number of copies of genes in the comparative genomic hybridation (CGH) analysis. The most common mutated gene was PIK3CA. Conclusion: All omic approaches must be integrated in the locally advanced cancer setting by new clinical trial design to develop two routes in the treatment strategy: intensification or de-escalation treatment strategy according to omic markers