HPV in Sentinel Lymph Nodes of Cervical Cancer Patients

Overview

This study examines sentinel lymph node tissue from early stage cervical cancer patients treated with radical surgery and removal of pelvic sentinel lymph nodes (SLN). SLNs are tested for the presence of human papilloma virus (HPV), and results are compared to the HPV-type found in the patient's cervical tissue. We hereby examine whether pathologic status of SLNs in patients with early-stage cervical cancer correlates to the HPV status in the SLNs. By means of an up to 5-years follow-up period, we furthermore examine whether cervical cancer recurrence correlates to the histopathologic status of the SLNs and/or the SLN HPV status. This will contribute to the clarification on whether HPV status of the SLNs plays a crucial role for predicting LN metastasis of cervical cancer and also, whether the HPV status in SLNs may have a clinical value as a prognostic factor for disease recurrence in cervical cancer patients and perhaps even a better clinical value than SLN mapping.

The aim of the study is to examine whether the pathologic status of SLNs in patients with early-stage cervical cancer correlates to the HPV status in the SLNs and also, whether cervical cancer recurrence correlates to the histopathologic status of the SLNs and/or the SLN HPV status. In Denmark, staging and treatment of cervical cancer are performed according to the recommendations of the International Federation of Gynecology and Obstetrics (FIGO). Cervical cancer is the only gynecological cancer that is clinically based on tumor size, vaginal or parametrial involvement, bladder/rectum extension and distant metastases. It requires examination under anesthesia and imaging, which in Denmark includes positron emission computed tomography (PET-CT) to detect pathological lymph nodes (LNs) and to accurately delineate the extent of the disease and magnetic resonance imaging (MRI) to determine tumor size, degree of stromal penetration, parametrial involvement, vaginal and corpus extension. Tumor risk assessment includes tumor size, stage, depth of tumor invasion, LN status, lymphovascular space invasion (LVSI) and histological subtype, of which LN status and number of LNs involved are the most important prognostic factors. In Denmark, patients at FIGO stages 1B1 to 2A undergo radical surgery and removal of SLNs, and these lymph nodes are examined by means of the ultrastaging protocol (see https://www.sciencedirect.com/science/article/pii/S0090825821005126?via%3Dihub). In this study, we want to examine the remains from these analyzed SLNs. Ultrastaging entails cutting the SLNs in more sections and all levels of the lymph node, and these levels are subsequently histologically analysed by an experienced pathologist. In this study, we examine the remains from the SLNs; that is the sections between the tissue used for SLN mapping. These sections are analyzed for HPV DNA by means of our in-house targeted Next Generation Sequencing panel (see https://febs.onlinelibrary.wiley.com/doi/10.1002/1878-0261.13538).