Persistent infection with high-risk human papillomavirus (hrHPV) types is a prerequisite for development of cervical dysplasia and cancer. During progression, deregulation and overexpression of viral proteins E6 and E7 occur, leading to loss of cell cycle control and neoplastic transformation. Current cervical cancer screening methods rely on cytological analyses compromised by frequent false-negative results and thus low sensitivity. HPV DNA-based tests pick up frequently infections without underlying disease leading to a low specificity. A more effective and reliable screening approach may involve exploitation of the oncoproteins E6 and E7 for specific detection of cervical dysplasia.
A hrHPV E7 sandwich ELISA – recomWell HPV 16/18/45 - was developed for detection of the hrHPV types 16, 18, and 45. Suitable for measurement of E7 protein are liquid-based cytological samples in PreserveCyte.
Sensitivity (CIN2+/CIN3+/CxCa: 36.1/58.3/85.7%), specificity (>98%), positive predictive value (PPV) (CIN2+/CIN3+/CxCa: 59.5/56.8/16.2%) and negative predictive value (NPV) (>97.5%) were calculated across all studies with 1572 clinical samples.
1473 samples were analyzed for validity of E7-based triage for HPV16/18 positive women. 282 women were positive for hrHPV DNA testing and further subjected to colposcopy. For the detection of CIN2+ for HPV16/18 positive women without further triage, sensitivity and PPV were 100.0% and 11.11%, respectively. No triage of HPV16/18 positive women required 9 colposcopies to diagnose one case of CIN2+. The sensitivity of recomWell HPV16/18/45 was 100.0% (meaning that no CIN2+ case was missed) and PPV was 19.75%. The recomWell HPV16/18/45 identified all 16 CIN2+ cases, requiring 43.75% less colposcopies than no triage of HPV16/18 positive women.
Detection of hrHPV E7 by ELISA is a feasible method for diagnosing HPV-induced, high-grade cervical dysplasia. Our results support the detection of HPV E7 oncoprotein as a method of triage to colposcopy for HPV16/18 positive women (instead of no triage) in the framework of a screening program based on primary HPV screening with HPV 16/18 genotyping.