Accuracy of HPV E6/E7 oncoprotein tests to detect high-grade cervical lesions: a systematic literature review and meta-analysis

Br J Cancer. 2024 Mar;130(4):517-525. doi: 10.1038/s41416-023-02490-w. Epub 2023 Nov 16.

Abstract

Background: Cervical carcinogenesis is mediated by the HPV-E6 and E7 oncoproteins, considered as biomarkers usable in managing screen-positive women.

Methods: We conducted a systematic review and meta-analysis assessing the accuracy of HPV-E6/E7-oncoprotein tests to detect underlying cervical-precancer and cancer. We included studies reporting data on oncoprotein test accuracy detecting cervical intraepithelial neoplasia grade 3 or worse. Random effects logistic regression models were applied for pooling absolute and relative accuracy.

Results: Twenty-two studies were included. Sensitivity and specificity estimates ranged from 54.2% (95%CI: 45.2-63.0) to 69.5% (95%CI:60.8-76.9) and from 82.8% (95%CI: 50.4-95.8) to 99.1 (95%CI: 98.8-99.3), respectively in the population irrespective of HPV status. Higher sensitivity estimates ranging from 60.8% (95%CI: 49.6-70.9) to 75.5% (95%CI: 71.7-78.9) but lower specificity estimates ranging from 83.7% (95%CI: 76.1-89.3) to 92.1% (95%CI: 88.5-94.6) were observed in studies enrolling high-risk-HPV-positive women. Studies recruiting only HIV-positive women showed a pooled sensitivity of 46.9% (95%CI: 30.6-63.9) with a specificity of 98.0% (95%CI: 96.8-98.7).

Conclusions: The high specificity of oncoprotein tests supports its use for triaging HPV-positive women. However, oncoprotein-negative women would not be recommended to undertake routine screening, requiring further follow-up. Large-scale and longitudinal studies are needed to further investigate the role of E6/E7-oncoprotein detection in predicting the risk of developing cervical pre-cancer and cancer.

Publication types

  • Meta-Analysis
  • Systematic Review
  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cervix Uteri
  • Female
  • Humans
  • Oncogene Proteins, Viral*
  • Papillomaviridae / genetics
  • Papillomavirus E7 Proteins
  • Papillomavirus Infections* / diagnosis
  • Uterine Cervical Dysplasia*
  • Uterine Cervical Neoplasms* / diagnosis

Substances

  • Oncogene Proteins, Viral
  • Papillomavirus E7 Proteins