Performance of an HPV 16/18 E6 oncoprotein test for detection of cervical precancer and cancer

• Published in: International journal of cancer 2019-10, Vol.145 (8), p.2042-2050
• Main Authors: Ferrera, Annabelle, Valladares, Wendy, Cabrera, Yessy, Hernandez, Maria, Darragh, Teresa, Baena, Armando, Almonte, Maribel, Herrero, Rolando
• Format: Article
• Language: English
• Subjects: Adult; Cancer; Cancer screening; Carcinogenicity; Cervical cancer; Cervical Intraepithelial Neoplasia - diagnosis; Cervical Intraepithelial Neoplasia - virology; Cervix; Colposcopy; Deoxyribonucleic acid; DNA; DNA, Viral - genetics; DNA-Binding Proteins - genetics; E6 oncoproteins; Early Detection of Cancer - methods; ESTAMPA; Female; Genotype; Honduras; HPV; Human papillomavirus; Humans; Immunohistochemistry; Lesions; Medical research; Medical screening; Middle Aged; Oncogene Proteins, Viral - genetics; Oncoproteins; Papillomaviridae - classification; Papillomaviridae - genetics; Papillomavirus Infections - diagnosis; Papillomavirus Infections - virology; Polymerase Chain Reaction - methods; Precancerous Conditions - diagnosis; Precancerous Conditions - virology; Repressor Proteins - genetics; screening; Sensitivity; Sensitivity and Specificity; Uterine Cervical Neoplasms - diagnosis; Uterine Cervical Neoplasms - virology
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.32156

HPV testing is a better alternative for cervical cancer screening, but additional procedures are required for triage of HPV positive women. HPV encoded oncoproteins E6 and E7, as the main effectors of HPV carcinogenicity represent promising triage alternatives. To evaluate performance of the test, we included 155 women from a screening study and 59 from the same referral population attending colposcopy and with precancerous lesions. All were HPV‐tested with HC2 and genotyped with LiPA, and cervical swabs were tested for HPV16/18 E6 oncoproteins. Histologic specimens were reviewed and adjudicated using p16 immunohistochemistry and 55 women had confirmed histologic HSIL, 31 (56.3%) associated with HPV 16/18, 23 with other HPV types and one HPV negative. Sensitivity and specificity were estimated with histologic HSIL/cancer as gold standard. E6 oncoprotein was detectable in all but one HSIL and in all cancers where HPV16/18 DNA was detected, but in none of the cases associated with other HPV types or HPV negatives. Among the few HPV16/18 DNA positive subjects initially without HSIL (n = 4) who were E6 oncoprotein positive, precancer was detected during follow‐up in 2 out of 3 with available information. Estimated sensitivity for HPV16/18‐related HSIL+ was 96.8% (95%CI = 83.8–99.8) and for all HSIL+ regardless of HPV type it was 56.4% (95%CI = 43.3–68.6). Specificity was 97.5% (95%CI = 93.7–99.0). E6 oncoprotein proved as a highly sensitive and specific marker for detection of HPV16/18‐related HSIL lesions in this Honduran population with limited previous screening and may be useful as a triage method in screening programs, particularly in low income countries. What's new? In Honduras, cervical cancer is the most common cancer among women, and cost‐effective triage methods are needed to identify women at risk. Here the authors tested the performance of the Onco E6 detection system, a simple antibody‐based test for high‐risk human papilloma virus (HPV) E6 oncoprotein expression in cervical swaps. The method was highly sensitive and specific for detection of lesions associated with HPV 16 and 18 in a high‐risk population of Honduran women, representing a possible addition to existing screening programs in low‐ and middle‐income countries.