Yu.Yu. Andreeva

Predictive immunotherapeutic markers of adenocarcinomas and adenosquamous carcinoma of the cervix

Adenocarcinoma and adenosquamous carcinoma of the cervix together account for up to 20% of all cervical cancers. These histologic subtypes are characterized by a worse prognosis compared with squamous cell cancer of the same grade and have specific epidemiologic, morphologic and molecular features. Despite fundamental differences, therapeutic approaches for cervical cancer are similar regardless of tumor histology. This article discusses promising companion diagnostic markers for cervical cancer treatment, including MSI, PD-L1 and TIL’s, that may find application in the therapy of prognostically unfavorable subtypes of cervical cancer. The literature review revealed that despite the low frequency of immunotherapy markers among adenocarcinomas and adenosquamous carcinomas of the cervix, analyzing them will allow us to identify a group of patients who will benefit most from immunotherapy, a key step towards improving treatment outcomes.

Predictive markers of immunotherapy in cervical cancer

Objective. Study of PD-L1 expression in squamous and adenosquamous cell cervical cancer (CC) by immunohistochemical (IHC) method, assessment of the relationship between PD-L1 tumor status and its clinical and morphological characteristics, TILs, MSI/dMMR, and HPV tumor status. Material and methods. Surgical material was obtained from 41 patients with CC, on which the expression of PD-L1, proteins of the MMR system and p16 was studied by the IHC method, the TILs index was determined. Results. Positive PD-L1 status was found in 51.2% of the studied CC samples. In the study sample, the level of PD-L1 expression depended on the severity of lymphoid infiltration of the tumor (p=0.038), it was shown that a positive PD-L1 status of CC can be expected with a TILs value greater than or equal to 50%. The age of the patients, the histological variant of the tumor, the pT and pN stage, the presence of lymphovascular invasion, and the HPV status did not statistically significantly affect the level of PD-L1 expression, however, there was an association between the PD-L1 status and the grade of CC malignancy (p=0.027). The presence of the MSI/dMMR phenomenon was detected in a small percentage of carcinomas (4.9%), the PD-L1 status of these tumors was determined as positive. Conclusion. A positive PD-L1 status is determined in a significant number of cases of CC, regardless of most of the studied clinical and morphological characteristics; there is a statistically significant relationship between PD-L1 expression and the degree of tumor differentiation and TILs. It has been shown that CC with the MSI/dMMR phenomenon is characterized by a positive PD-L1 status. The authors consider it necessary to study the expression of PD-L1 in patients with cervical carcinomas in order to determine the possibility of prescribing personalized therapy with immune checkpoint inhibitors.