The value of cytokine levels in triage and risk prediction for women with persistent high-risk human papilloma virus infection of the cervix

Bohan Li; Ling Zhang; Jianguo Zhao; Guichun Tan; Wenwen Zhang; Na Zhang; Jing Tian; Pengpeng Qu

doi:10.1186/s13027-019-0231-z

The value of cytokine levels in triage and risk prediction for women with persistent high-risk human papilloma virus infection of the cervix

Infect Agent Cancer. 2019 Jun 28:14:16. doi: 10.1186/s13027-019-0231-z. eCollection 2019.

Authors

Bohan Li¹, Ling Zhang², Jianguo Zhao¹, Guichun Tan³, Wenwen Zhang¹, Na Zhang¹, Jing Tian¹, Pengpeng Qu¹

Affiliations

¹ 1Tianjin Central Hospital of Gynecology and Obstetrics, No. 156, Nankaisan Road, Nankai District, Tianjin, China.
² Cang Zhou Central Hospital, No. 16 Xinhuaxi Road, Yunhe District, Cangzhou, Hebei China.
³ 3Tianjin Medical University, No. 22, Qixiangtai Road, Tianjin, Heping District China.

Abstract

Background: Cervical cancer is a common cancer among women worldwide and is closely related to high-risk human papillomavirus infection (HR-HPV). The immune microenvironment is thought to play an essential role in viral infection and cancer development; however, this relationship remains controversial. Cytokines are an important part of the immune system. Therefore, in this study, we explored changes in cervical cytokine levels of women with persistent HR-HPV infection and determined the value of cytokine detection in assessing cervical lesions.

Methods: We enrolled 146 patients; 117 had long-term high-risk (HR) HPV infection (> 6 months), and 29 were HPV-negative with previous HR-HPV infection. According to histopathological examination, 43 patients were diagnosed with cervicitis; 35, with low-grade squamous intraepithelial lesions (LSILs); and 39, with high-grade squamous intraepithelial lesions (HSILs). Cytokine levels in vaginal fluid were examined using cytometric bead array, and the values of interleukin (IL)-6 and IL-2 levels were converted to a cytokine score. The performance of the cytokine score for diagnosis and risk assessment was compared with that of ThinPrep cytology tests (TCTs).

Results: Disease severity was positively associated with IL-6 levels and inversely related to IL-2 levels. The area under the curve (AUC) was higher for the cytokine score including IL-6 and IL-2 than for TCTs for HSILs. Comparisons of the sensitivity, specificity, Youden index, and positive and negative predictive values for HSILs demonstrated that the cytokine score was better than TCT. HPV-positive patients with high cytokine scores showed increased risk of developing HSIL within 3 years. The hazard ratio for the cytokine score was 3.12; thus, the risk of developing HSIL was related to the cytokine score.

Conclusions: The cytokine score increased with the severity of cervical lesions and could distinguish more patients from HPV-positive women and predict the risk of disease progression.

Keywords: Cervical lesions; Cytokines; Flow cytometry; High-grade squamous intraepithelial lesion; Triage.