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

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.

Predictive Value of HPV E6/E7 mRNA Detection on the Outcome of Cervical LSIL

“…HR-HPV E6/E7 mRNA test is a promising noninvasive biomarker; compared with the HPV DNA test, HPV mRNA test and DNA test are in good agreement, in the detection of high-grade cervical lesions (CIN II+). It has similar sensitivity and higher specificity, suggesting that it can not only detect HPV infection but also predict changes in cervical lesions [ 13 , 14 ]. Ratnam et al [ 15 ] claimed that detection of HPV E6/E7 oncogene expression may be more predictive of cervical cancer risk than detection of HPV DNA.…”

Evaluation of HPV E6/E7 mRNA Detection in Clinically Suspected Cases of Cervical Cancer with Abnormal Cytology: Time to Upgrade the Screening Protocols

“…In our study, 36 patients had ASC-US cytological findings on PAP smear, but none of them showed HPV E6/E7 mRNA expression and also these patients had normal biopsy findings. A recent study done by Zhang et al 26 showed that HPV DNA, mRNA, increased with the severity of histopathology diagnosis, from 25.5%, 19.1%, in normal to 100.0% in squamous cell carcinoma, respectively. In our study HPV E6/7 mRNA has higher specificity (100%) and positive predictive value (100%) as compared with HPV DNA.…”

Anal Cancer and Anal Cancer Screening

“…Therefore, it has been suggested that a positive HPV E6/E7 mRNA result is more likely than detection of HPV DNA to reflect the presence of squamous intraepithelial lesions. 70,71 Of the 6 studies evaluating HPV E6/E7 mRNA in the systematic review, performance was similar to dual stain cytology (lower sensitivity, but higher specificity) with summary sensitivity and specificity estimates of 74% and 64%, respectively. Variable performance among the studies is likely due to differences in the assays (particularly, HPV type coverage), among other factors.…”