Laura Downham

Field experience with the 8‐HPV‐type oncoprotein test for cervical cancer screening among HPV‐positive women living with and without HIV in LMICs

AbstractOverexpression of HPV‐oncoproteins E6 and E7 is necessary for HPV‐driven cervical carcinogenesis. Hence, these oncoproteins are promising disease‐specific biomarkers. We assessed the technical and operational characteristics of the 8‐HPV‐type OncoE6/E7 Cervical Test in different laboratories using cervical samples from HPV‐positive women living with (WLWH) and without HIV. The 8‐HPV‐type OncoE6/E7 Test (for short: “OncoE6/E7 test”) was performed in 2833 HIV‐negative women and 241 WLWH attending multicentric studies in Latin America (ESTAMPA study), and in Africa (CESTA study). Oncoprotein positivity were evaluated at each testing site, according to HIV status as well as type‐specific agreement with HPV‐DNA results. A feedback questionnaire was given to the operators performing the oncoprotein test to evaluate their impression and acceptability regarding the test. The OncoE6/E7 test revealed a high positivity rate heterogeneity across all testing sites (I2: 95.8%, p < .01) with significant lower positivity in WLWH compared to HIV‐negative women (12% vs 25%, p < .01). A similar HPV‐type distribution was found between HPV DNA genotyping and oncoprotein testing except for HPV31 and 33 (moderate agreement, k = 0.57). Twenty‐one laboratory technicians were trained on oncoprotein testing. Despite operators' concerns about the time‐consuming procedure and perceived need for moderate laboratory experience, they reported the OncoE6/E7 test as easy to perform and user‐friendly for deployment in resource‐limited settings. The high positivity rate variability found across studies and subjectivity in test outcome interpretation could potentially results in oncoprotein false positive/negative, and thus the need for further refinements before implementation of the oncoprotein testing in screen‐triage‐and‐treat approaches is warranted.

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

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.