HPV-16 E2/E6 and POU5F1B as Biomarkers to Determine Cervical High-Grade Squamous Lesions and More

Lihua Chen; Binhua Dong; Hangjing Gao; Huifeng Xue; Diling Pan; Pengming Sun

doi:10.2147/JIR.S278911

HPV-16 E2/E6 and POU5F1B as Biomarkers to Determine Cervical High-Grade Squamous Lesions and More

J Inflamm Res. 2020 Oct 29:13:813-821. doi: 10.2147/JIR.S278911. eCollection 2020.

Authors

Lihua Chen^#^{1

2}, Binhua Dong^#^{2

3}, Hangjing Gao^{2

3}, Huifeng Xue⁴, Diling Pan⁵, Pengming Sun^{1

2

3}

Affiliations

¹ Department of Gynecology, Fujian Provincial Maternity and Child Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, People's Republic of China.
² Fujian Provincial Key Laboratory of Women and Children Major Disease, Fujian Provincial Maternity and Child Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, People's Republic of China.
³ Laboratory of Gynecologic Oncology, Fujian Provincial Maternity and Child Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, People's Republic of China.
⁴ Medical Center of Cervical Disease and Colposcopy, Fujian Provincial Maternity and Child Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, People's Republic of China.
⁵ Department of Pathology, Fujian Provincial Maternity and Child Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, People's Republic of China.

^# Contributed equally.

Abstract

Purpose: Human papillomavirus-16 (HPV-16) is the most carcinogenic HPV genotype. This study aimed to evaluate the clinical value of POU5F1B and HPV-16-E2/E6 by cervical cytology specimens to predict the cervical intraepithelial neoplasia two grade and more (CIN2+).

Methods: Finally, 248 patients with HPV-16 single infection were enrolled. Using cytology specimen by real-time quantitative PCR (qPCR), POU5F1B mRNA and HPV-16-E2/E6 were detected. The relationship of POU5F1B, HPV-16-E2/E6 and CIN2+ were analyzed, and the optimal cut-off values of POU5F1B and HPV-16-E2/E6 to predict CIN2+ were calculated.

Results: The mean HPV-16-E2/E6 decreased signiﬁcantly with cervical lesions development, especially compared with CIN2+ (p<0.05). And the POU5F1B demonstrated higher expression in CIN2+ than that of normal cervical tissue and CIN1 (p<0.05). What is more, POU5F1B was negatively correlated with HPV-16-E2/E6. It demonstrated that the area under the receiver operating characteristic curve (AUC) for POU5F1B (0.9058) was higher than that for HPV-16-E2/E6 (0.8983), and the sensitivity and specificity of POU5F1B in the diagnosis of CIN2+ were higher than HPV-E2/E6. Furthermore, it demonstrated that the POU5F1B had the highest odds ratio (OR= 16.84; 95% CI (8.00-35.46)) for the detection of CIN 2+.

Conclusion: HPV-16-E2/E6≤0.6471 or POU5F1B≥1.0310 in cervical exfoliated cells can be used as a reliable predictor of CIN2+. POU5F1B can be used as a new auxiliary biomarker to determine the HPV infection status and a reliable predictor of CIN2+. The expression of POU5F1B≥1.0310 had the highest OR for the detection of CIN2+.

Keywords: HPV integration; HPV-E2/E6; POU5F1B; cervical intraepithelial neoplasia; human papillomavirus type 16.

Grants and funding

The study was supported by grants from the Fujian Provincial Maternity and Children’s Hospital Technology Innovation Project (grant no. YCXM-19-01) and Fujian Provincial Health and Family Planning Commission Innovation Project (2019-CX-7).