**9. Ongoing clinical trials and future perspectives**

On October 2021, the highly anticipated KEYNOTE-826 trial confirmed that there was a survival benefit of adding immunotherapy in the form of a drug called Pembrolizumab to chemotherapy for patients with persistent, recurrent, or metastatic cancer. The KEYNOTE-A18 trial is an ENGOT (European Network for Gynecological Oncological Trial groups) and GOG partners collaboration. It is a randomized phase 3 trial with chemoradiotherapy with or without pembrolizumab for high-risk locally advanced cervical cancer. And 980 patients are anticipated to receive pembrolizumab on day 1 of a 3-week cycle for 5 cycles, followed by pembrolizumab on day 1 of a 6-week cycle for 15 cycles. The primary outcome is progression-free survival (PFS) and overall survival (OS) [43]. Dr. Tewari is researching high-risk individuals, patients with stage IIIB or IIIC positive lymph nodes, or even aortic nodes, and has randomized them to chemotherapy, radiation, placebo versus durvalumab, added both in the radiation phase and the maintenance phase for up to 24 months. This study is known as CALLA, and it is enrolled. There are 714 subjects listed on clinicaltrials.g ov, and the trial has been closed since December 2020 [44].

In addition, the currently approved therapies for cervical cancer are accompanied by debilitating side effects and tumor drug resistance. This is the case despite significant breakthroughs in the utilization of combination medicines. To increase the efficacy of single-agent therapies for cervical cancer, there is a pressing need to discover new and better medications. Immunotherapy, targeted therapy, and genetic methods such as CRISPR/Cas9 and RNAi are among the various cervical cancer therapies now under investigation. These are only a few instances of the treatment options available. Chemotherapy and radiation therapy are other treatment choices to explore. The majority of these therapies are still in the research phase, and the alternatives they provide are more costly. Identification of non-cancer medicines that target host factors that, in conjunction with HPV oncoproteins, notably E6 and E7, promote cervical cancer progression is one method that may lead to timely medication development at an acceptable and cheap price. This strategy, which combines a targeted approach with medication redirection, is appealing because it should find pharmaceuticals with far fewer adverse effects than conventional cancer therapies. This makes the idea more appealing. Due to the extensive study of their safety profiles, it is anticipated that they will enter clinical trials quickly [45].
