Detection of CDR3s diversity and its prediction of persistent high-risk HPV infection and cervical intraepithelial neoplasia risk: a prospective study

Abstract

Background: We aimed to determine the potential role of complementarity-determining region 3s (CDR3s) in prognosis of high-risk HPV (hr-HPV) infections and cervical intraepithelial neoplasia (CIN) in a prospective study for 12 months. Methods: Twenty-six women aged 30–64 years were recruited using cytology and HPV DNA test in China. After obtaining written informed consent, our team utilized ARM-PCR and second-generation high throughput sequencing to detect the diversity 50 (D50) value of CDR3s diversity among the groups of cancer (n=5), CIN 2/3 (n=4), CIN 1 (n=6), hr-HPV positive (n=8) and normal control (n=3) at the baseline year. Additionally, cytology and HPV DNA test adopted to the groups of CIN 1 and hr-HPV found the status of cervical lesions and hr-HPV infected persistence between CIN 1 (n=6) and hr-HPV (n=7) groups. Results: The prevalence of CDR3s diversity staining was 9.2±7.9, 5.7±5.6, 4.0±6.0, 13.6±7.7, 8.0±7.6 among women with normal, hr-HPV positive, CIN 1, CIN 2/3 and cancer biopsies. Decreased CDR3s diversity were not significantly associated with disease progression (P=0.093). There is no significant difference between CDR3s diversity and HPV clearance (P=0.173). All CIN1 cases regressed. Conclusions: CDR3s might be a biomarker to predict HPV-positive outcomes. The detection of CDR3s may assist in the clinical management of CIN 1. Women with CIN 1 and decrease of CDR3s diversity may benefit from closer follow-up at frequently intervals. (The trial registration number in Chinese Clinical Trial Registry: ChiCTR2000038164 and date of registration: September 11, 2020). 9