The Potential Benefits of HPV E6/E7 mRNA Test in Cervical Cancer Screening in China.

Peng Wang,Ze-Ni Wu,Pei-Pei Guo,Dong-Mei Zhao,Xi-Bin Sun,You-Lin Qiao,Man-Man Jia,Qiong Chen,Xiao-Qin Cao,Jian-Gong Zhang,Shao-Kai Zhang,Le-Ni Kang,Zhen Guo

doi:10.3389/fonc.2020.533253

Abstract

This study aims to evaluate the clinical performance of the HPV E6/E7 mRNA test in cervical cancer screening in China. A hospital-based study was conducted with mRNA, DNA, and liquid-based cytology (LBC) as primary screening tests. Each woman with a positive result received colposcopy with lesion-targeted-biopsy. Histopathological diagnosis was used as the gold standard. The total agreement of HPV DNA and mRNA was 90.7% (95%CI: 87.9, 92.9) with a kappa value of 0.81. The positive rates of HPV DNA, mRNA, and LBC increased with the severity of histopathology diagnosis, from 25.5, 19.1, and 11.4% in normal to 100.0% in SCC, respectively. The sensitivities for mRNA to detect CIN2+ and CIN3+ were 93.8% (95%CI: 89.7–96.4) and 95.7% (95%CI: 91.3–97.9), respectively, which were not different from HPV DNA testing (95.7% [95%CI: 92.0–97.7], 96.3% [95%CI: 92.1–98.3]), but higher than LBC (80.4% [95%CI: 74.5–85.2] and 88.8% [95%CI: 83.0–92.8]). The specificities for mRNA to detect CIN2+ (79.0% [95%CI: 74.2–83.0]) and CIN3+ (70.5% [95%CI: 65.7–74.9]) were higher than HPV DNA testing (71.0% [95%CI: 65.9–75.7], 62.8% [95%CI: 57.8–67.5]), but lower than LBC (84.5% [95%CI: 80.1–88.0] 79.8% [95%CI: 75.4–83.6]). All tests were more effective in women older than 30 years. HPV mRNA test showed excellent agreement with the DNA test, with similar sensitivity and a higher specificity in detecting high-grade cervical lesions. It is promising that mRNA test could be used for the national cervical cancer screening to reduce false positive without losing sensitivity.

Highlights

It is known that persistent infection with high-risk human papillomavirus is a necessary cause for cervical cancer and precancerous lesions [1, 2]
We evaluated the clinical performance of the HPV E6/E7 mRNA test to detect high-grade cervical intraepithelial neoplasia (CIN) and cancer among Chinese women
Specificities for mRNA to detect CIN2+ (79.0% [95% confidential intervals (95%CI): 74.2– 83.0]) and CIN3+ (70.5% [95%CI: 65.7–74.9]) were significantly higher than those detected by DNA (71.0% [95%CI: 65.9–75.7] for CIN2+, 62.8% [95%CI: 57.8–67.5] for CIN3+) (p < 0.05), but lower than those detected by liquid-based cytology (LBC) (84.5% [95%CI: 80.1– 88.0] for CIN2+, 79.8% [95%CI: 75.4–83.6] for CIN3+)

Summary

Introduction

It is known that persistent infection with high-risk human papillomavirus (hr-HPV) is a necessary cause for cervical cancer and precancerous lesions [1, 2]. Developed countries have begun to use hr-HPV testing in primary cervical cancer screening, either alone or co-testing with cytology [5,6,7,8]. Evidence shows that HPV-based screening programs provide greater protection against cervical pre-cancer and cancer than other traditional screening methods, such as cytology [9,10,11]. Since most HPV infections could be cleared spontaneously, HPV-testing identifies numerous infections that will not progress to cervical pre-cancer or cancer, especially in young women [12]. HPV DNA testing is not recommended to screen women under the age of 30. HPV-positive patients referred for subsequent procedures may suffer from unnecessary invasive interventions

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