Analysis Of Circulating Tumor DNA In Early Cervical Cancer And Its Correlation With Clinicopathologic Features

Objective:To analyze the copy number variation and content distribution of plasma circulating tumor DNA before initial treatment in early cervical cancer patients,to study the relationship between plasma circulating tumor DNA content and clinicopathological features before initial treatment;to monitor changes of plasma circulating tumor DNA content after surgery,after treatment and during follow-up,to explore the role of changes in plasma circulating tumor DNA content in the monitoring of early cervical cancer recurrence during follow-up after treatment.Methods: Thirty-three patients with early cervical cancer diagnosed by cervical biopsy were enrolled between March 2017 and September 2018.Among them,27 patients with early cervical cancer underwent surgery,6 cases of cervical cancer IIA2 patients refused surgery and received concurrent radiochemotherapy.General clinical pathology data of 33 patients with early cervical cancer were collected before initial treatment,including age,HPVE6E7 mRNA copy number,tumor diameter,squamous cell carcinoma antigen level,HPV classification,clinical stage,histological grade,histological classification,10 ml of elbow venous blood was extracted from each enrolled early cervical cancer patient for plasma circulating tumor DNA detection.Subsequently,27 patients with early cervical cancer were treated with surgery,and of which the surgical pathology data were collected,including lymph node metastasis,parametrial infiltration,surgical margin,lymphatic vessel infiltration,depth of cervical interstitial infiltration,10 ml of elbow venous blood was extracted 2 weeks after surgery for plasma circulating tumor DNA detection.Patients with early cervical cancer after surgery were treated with adjuvant therapy based on the presence or absence of intermediate and high risk factors.10 ml of elbow venous blood was extracted 4 weeks after the end of treatment from patients receiving adjuvant therapy.Subsequently,patients with early cervical cancer after the end of treatment were followed up.During the follow-up period,10 ml of elbow venous blood was taken every 6 months(no signs of recurrence)to detect plasma circulating tumor DNA.If there is any sign of recurrence,10 ml of elbow venous blood should be taken for plasma circulating tumor DNA detection at any time.The next-generation sequencing technology was used to detect the DNA chromosome copy number variation and content of plasma circulating tumors and further data analysis.Results:Among the 33 patients with early cervical cancer,16 patients with early cervical cancer before initial treatment had chromosome copy number variation,and the copy number of plasma circulating tumor DNA was 48.48%.Among them,3q amplification was the most common copy number variation;The content of plasma circulating tumor DNA was positive in 13 patients with early cervical cancer before initial treatment,and the detection rate was 39.39%;The content of plasma circulating tumor DNA in patients with early cervical cancer was correlated with tumor diameter,clinical stage,depth of cervical interstitial invasion,tissue differentiation degree and HPV infection,the difference was statistically significant(P<0.05);The content of circulating tumor DNA in patients with early cervical cancer was negative after surgery and the end of treatment;During the follow-up period,2 patients with recurrent cervical cancer were positive for plasma circulating tumor DNA.Conclusion: There are chromosome copy number variations in plasma of patients with early cervical cancer,3q amplification is the most common copy number variation,and circulating tumor DNA content can be detected in plasma of some patients;The plasma circulating tumor DNA content of early cervical cancer patients before the initial treatment is related to the tumor diameter,which can reflect the tumor burden to a certain extent;The content of plasma circulating tumor DNA before the initial treatment was correlated with clinical stage,depth of interstitial invasion,degree of tissue differentiation,and HPV infection;Increased circulating tumor DNA levels were detected in plasma of patients with early cervical cancer who had relapsed during follow-up,which may be of guiding significance in the monitoring of recurrence of early cervical cancer patients.