Using Whole Genome Sequencing Technique In The Exfoliative Cells Of Cervical Cancer As An Effective Tool For Cervical Cancer Detection

Objective:Cervical cancer is the second most common cancer in women after breast cancer.Cervical cancer screening has made a significant difference in reducing the incidence and mortality rate of cervical cancer.C urrently.the main screening methods includes the thinprep cytologic test,human papilloma virus detection,electronic colposcopy,etc.Different methods have their advantages and disadvantages.The purpose of this study is to analyze the chromosomal-arm-level copy number alterations(CNAs)in the cervical exfoliative cell and tissue samples by using the low-coverage whole genomic sequencing technique.Methods:In this study,we retrospectively collected 196 patients(61 in the model group and 135 in the verification group)in the Qingdao municipal hospital from January 1,201 8 to April 31,2018.The model group selected a total of 61 patients who are under surgical treatment in the Qingdao municipal hospital for cervical cancer or benign disease from January 1 2018 to January 31 2018.The model group is used to establish model.A total of 135 patients who underwent surgical treatment for cervical cancer or total hysterectomy for benign diseases or cervical cone resection tor cervical intraepithelial neoplasia in the gynecological ward of Qingdao municipal hospital were selected as the validation group to verify the efficacy of the model from February 1 to April l.20O 8.We analyzed the CNAs in cervical exfoliated cell and tissue samples by using the low-coverage next generation of sequencing to judge whether the CNAs changes in cervical exfoliated cell the same with tissue samples.Meanwhile,we established a model(C-score)to describe the chromosomal changes in the tumor group and non-tumor group.The model was test in the validation group to detect the sensitivity and specificity.Results:In the retrospective study,multiple chromosomal-arm-level CNAs were detected in both cervical exfoliated cell and tissue samples of all cervical cancer cases.By statistical analysis,it was found that the same variation trend of chromosole copy number in tissue and exfoliated cells.Considering the influence of pathological typing on chromosome copy number changes,the model group was divided into cervical squamous cell carcinoma group and cervical non-squamous cell carcinoma group for whole genome sequencing.ln the cervical squamous cell carcinoma group,the most of samples were discoverd the chromosomal arm-level changes of 3p,5q and 11q.In the cervical non-squamous cell carcinoma group,the copy number variation of chromosome 17 and 18 was more obvious.According to chromosome copy number variation,a c-score model was constructed.And it was considered that if the C-score model>0,the samples was positive and the sample was a tumor specimen.Data from an independent validation set including 135 samples demonstrate a sensitivity of 94.7%and a specificity of 96.6%.Data from both the model set and validation set including 196 samples demonstrate a sensitivity of 97.7%and a specificity of 97.4%.Conclusions:In this study,we found that the same variation trend of chromosome copy number in both the cervical exfoliated cells and tumor tissues.Therefore,the detection of the chromosome copy nunber of the cervical exfoliated cell sample can predict whether the patient has cervical malignant tumor.Through statistical analysis,it was found that the C-score model was highly sensitive and specific.The C-score model has higher accuracy and specificity than the thin-laver liquid-based cytology.However.the C-socre also has disadvatage that the C-score can not distinguish the cervical intraepithelial neoplasia Ⅲ with cervical cancer,and specific pathological types such as transparent cell adenocarcinoma.In the future,it is necessary-to expand the sample and find more copy number variations of different chromosomes,so as to further improve the C-score model accuracy and specificit’.To sum up,the clinical value of-whole genome sequencing of exfoliated cervical cells in cervical cancer screening methods has been preliminarily confirmed,which is expected to open up a new way for cervical cancer screening.