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

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.