2.1 Study population
This study included 1,713 patients with pathologically confirmed uterine cervical carcinoma, who underwent radical hysterectomy between January 2008 and December 2018 at the First Affiliated Hospital of Wenzhou Medical University, China. The following exclusion Criteria was used: (1) Women who received any drugs that impacted lipid metabolism; (2) Patients with chronic diseases that effected lipid levels (i.e., diabetes); 3) Patients received any treatments before serum collection. Information mentioned above was obtained from the electronic medical records. Besides, the control group included 10,397 healthy women. This study was approved by the Ethics Committee of the First Affiliated Hospital of Wenzhou Medical University and informed consent was signed by the patients before taking part in this study. A detailed review of patient history, general physical examination, pelvic examination (including bimanual pelvic and rectal examinations), preoperative laboratory (plasma lipid profiles, and SCC-Ag ), pathological data (metastasis, stage, and differentiation) of all patients were collected from electronic medical records and reviewed. Detailed clinical data were collected within one week before operation. Preoperative plasma levels of HDL, LDL, TC, TG, and serum squamous cell carcinoma antigen (SCC-Ag) were measured in early morning before surgical operation and immediately measured using a Hitachi 7600-020 automatic biochemical analyzer with the kinetic method [11]. Body mass index (BMI) was calculated as body-weight(kg)/height(m)2.
All of 1,713 cervical cancer patients were classified as high-risk, intermediate-risk, and low-risk after postoperative pathological evaluation. High-risk patients defined as the presence of tumor involvement of the parametria, positive margins, or lymph node metastases [14]. Intermediate risk factors included depth of invasion, lymphovascular space invasion, and tumor size [15]. Patients without high and intermediate risk factors are defined as low-risk.
Besides, we collected age, BMI, plasma levels of HDL, LDL, TC, TG from 10,397 healthy women as control. Given that lipid levels were affected by confounders such as age and BMI, we matched the healthy women group and the cervical cancer group with age, with every 10 years as a subgroup. Then, by randomly matching the healthy control group and the cancer group with a ratio of 2: 1, we obtained 3,426 healthy women. We then controlled the potential confounders (age and BMI) by regression analysis and analyzed the difference of lipid levels between healthy group and cancer group.
Follow-up examinations were performed every 3 months in the first 2 years, and then every 6 months for the next 3 years and every 1 year thereafter. Pelvic examination, cytology, the serum concentration of SCC-Ag, and imaging studies including Computed Tomography, Magnetic Resonance Imaging, or Positron Emission Tomography-Computed Tomography, were performed during routine follow up.
The last follow-up date was July 15, 2019. The end points of this study were overall survival (OS) and recurrence-free survival (RFS). Overall survival was determined from the date of surgery to death or last follow-up. Recurrence-free survival (RFS) was calculated from the date of surgery to the tumor recurrence or distant metastasis.