Advances in management algorithm in clear cell carcinoma of cervix

Abstract

Abstract This comprehensive review critically assesses tailored management strategies for clear cell carcinoma of the cervix (cCCC), an uncommon subtype of cervical adenocarcinomas. A globally prevalent condition, cCCC affects individuals across diverse racial and ethnic groups. Notably, a significant risk factor associated with cCCC is intrauterine exposure to diethylstilbestrol (DES), a synthetic estrogen historically prescribed to address pregnancy-related complications. Intriguingly, almost two-thirds of cCCC cases are linked to DES exposure. Studies reveal a notable surge in cCCC incidence among offspring born to women administered DES during pregnancy, with DES-exposed daughters facing a staggering 40-fold higher risk compared to their non-DES-exposed counterparts. Turning to the molecular intricacies of cCCC, gene expressions within this subtype exhibit intriguing parallels with clear cell carcinomas found in the ovary, endometrium, and kidney. Additionally, there is a noteworthy exploration of cervical endometriosis as a potential precursor to cCCC. Molecular pathways, specifically the PI3K/AKT and Hippo pathways, have garnered attention in understanding the pathogenesis of cCCC. From a prognostic standpoint, disparities emerge, with non-DES-related cCCC cases generally exhibiting a grimmer prognosis than their DES-related counterparts. This discrepancy becomes starkly evident in advanced disease stages. Early detection proves crucial, as patients diagnosed in initial stages experience commendable outcomes, markedly superior to those facing advanced or recurrent manifestations. Fertility-preserving treatments are highly endorsed for early-stage patients. Simultaneously, the therapeutic landscape is evolving, with PD-L1 inhibitors gaining prominence as a burgeoning treatment modality, particularly beneficial for those navigating advanced stages of cCCC. Furthermore, the combination of PARP inhibitors (PARPi) and immune checkpoint inhibitors (ICI) emerges as a promising and innovative treatment alternative for cCCC. In summary, this review encompasses a detailed exploration of cCCC, spanning risk factors, molecular intricacies, prognostic considerations, early detection strategies, and evolving treatment modalities, presenting a comprehensive understanding of the management approaches tailored for this unique subtype of cervical adenocarcinomas.

Keywords

• Cervical cancer
• Clear cell carcinoma
• HPV-independent adenocarcinoma
• Treatment regimens