Management of Cervical Cancer in the Era of Precision Medicine

Keerthi Ranganathan

Scientific Content Developer
4baseCare

According to WHO GLOBOCAN 2020, cervical cancer (CC) is one of the most often diagnosed malignancies in women, accounting for 6.5 percent of cancer cases and 7.7 percent of fatalities. It is the fourth most common cancer in women, with 604,127 cases and 341,831 deaths globally (Poondla et al 2020).

Patients with recurrent or metastatic cervical cancer have a poor prognosis, with a 5-year survival rate of about 17%. Surgery, radiotherapy, systemic therapy, or a combination of these therapeutic modalities are all considered standard of care in cervical cancer management based on clinical stage categories at diagnosis. However, clinical outcomes remain poor, especially in locally advanced and recurrent/metastatic disease.

Cervical cancers pathogenesis is triggered when the human papillomavirus (HPV) infects the host, resulting in tumor suppressor gene inactivation and oncogene activation, supporting the development of immunotherapy in cervical cancer (Marret et al, 2019).

Molecularly targeted agents in CC are still being tested in clinical trials. Patients with Cervical Cancer can have a wide range of outcomes, and certain genetic variants have been demonstrated to influence clinical response to conventional treatment. Therefore, precision medicine trials include (1) adding targeted medicines to conventional therapies based on single molecular alterations and/or tumor types, and (2) algorithm testing in late-stage tumor types.

The concepts of immunotherapy and non-specific immune treatments have made significant progress in the treatment of cervical cancer. Monoclonal antibodies directed against a particular protein in cancer cells that are not found in normal cells are used in immunotherapy to target cancer-specific cells. For instance, immunotherapy drugs target Programmed cell death protein 1 (PD-1) expression is used to select patients with cervical cancer for treatment with checkpoint inhibitors.

Chimeric antigen receptor modified-T cells (CAR-T) cell treatment, a type of immunotherapy that uses and improves the immune system’s intrinsic potential, is one of the most promising techniques in recent years. In this, the participant’s T-cells are collected and genetically modified (CAR T) which can recognize specific molecules that are expressed on the surface of cervical cancer cells and are then given back to the participant by intravenous infusion. Once in the body, the CAR T cells can further grow to large numbers, persist for long periods of time, and provide ongoing tumor control and possible protection against recurrence.

Chung et al. (2019) investigated the antitumor activity and safety of pembrolizumab in previously treated patients with advanced cervical cancer. The authors analyzed cervical cancer subpopulation in phase II KEYNOTE-158 basket study. In patients with advanced cervical cancer, pembrolizumab monotherapy showed long-term anticancer efficacy and acceptable tolerability. The US Food and Drug Administration granted pembrolizumab expedited approval based on these findings for patients with advanced programmed death-ligand 1 (PD-L1)-positive cervical cancer who experienced progression during or after chemotherapy.

Furthermore, BIO-RAIDs, a prospective multicenter European trial with extensive bio-banking, are being used to find predictive biomarkers for cervical cancer therapy response. By defining a set of stratification criteria for cervical carcinomas and other malignancies with comparable genetic changes, BIO-RAIDs will provide the groundwork for future precision medicine investigations (Ngo et al 2015).