E6/E7 proteins are potential markers for the screening and diagnosis of cervical pre‑cancerous lesions and cervical cancer in a Chinese population

Abstract

Abstract. The present prospective study aimed to evaluate the effects of E6/E7 protein detection by western blotting on cervical cancer (CC) early screening compared with detection by Hybrid Capture 2 (HC2) test and ThinPrep cytological test (TCT) in a Chinese population. A total of 450 cases of cervical intraepithelial neoplasia (CIN) suspected samples (positive in ≥1 indicator of TCT and HC2 test) were recruited from women who were treated at the International Peace Maternity and Child Health Hospital (Shanghai, China) from March 2014 to February 2015. Each sample was analyzed by cytological test. In addition, human papillomavirus (HPV) DNA examination by Hybrid Capture Tube test and E6/E7 protein expression detection by western blotting were performed in all samples, as well as histologic diagnosis to determine the stage of CIN. The results revealed that, for the diagnosis of CIN2 + , although the sensitivity of E6/E7 protein detection was lower than that of HC2 test (71.3 vs. 96.6%, respectively), the specificity was markedly improved (67.6 vs. 5.9%, respectively). Compared with that of TCT, the sensitivity of E6/E7 protein detection was much higher (36.2 vs. 71.3%, respectively), but the specificity was lower (88.2 vs. 67.6%, respectively). In the present study, HPV E6/E7 protein expression was evaluated as a potential new biomarker for CC, with satisfactory diagnostic values for HPV types 16 and 18. The relative diagnostic value may be further improved by combination of E6/E7 messenger RNA detection.

Genome-Wide Profiling of Human Papillomavirus DNA Integration into Human Genome and Its Influence on PD-L1 Expression in Chinese Uygur Cervical Cancer Women

“…(1) Chip Design and Order. We designed the sequencecapture probes according to 20 types of HPV genome (6,11,16,18,31,33,35,39,42,43,44,45,51,52,53,56,58,59, 66, and 68) sequences, and these probes were produced by Agilent Inc., USA. The enrichment chip was also ordered from Agilent Inc., USA.…”

“…In immature epithelial cells, HPV E6 and E7 gene began to have uncontrolled expression, and the excessive expression of E6 and E7 protein would, respectively, combine with the gene products of p53 and Rh, which led to the immaturity of cervical epithelial cells; meanwhile, the viruses could not complete the whole life cycle, the L1 protein expression was missing, the infection cells created immune escape, the virus could not be cleared by the immune system, the immaturity of cervical epithelial cells led to immortalization, and lastly, it caused the lesions and canceration of cervical cells. Due to the fact that the HPV gene into the human genome was the key step in cervical cancer occurrence, so to explore the integration sites of HPV genome into the human genome and the integrated position influence on human cell genome had important clinical significance [5][6][7].…”

Understanding the Role of Intrinsic Disorder of Viral Proteins in the Oncogenicity of Different Types of HPV

“…Based on data published by the International Agency for Research on Cancer and the World Health Organization [ 13 , 14 ], 15 types of high-risk HPVs most frequently related to cancer, and 12 types of low-risk HPVs most frequently related to benign lesions, were chosen. A type of HPV, related to neither cancer nor benign lesions [ 13 ], was chosen as a control in the analyses ( Table 1 ).…”

“…The different types are divided into two groups namely High- and Low-Risk, based on their oncogenic potential. According to reports by the International Agency for Research on Cancer and the World Health Organization, HPVs of high oncogenic risk in humans are: types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 66 due to their high prevalence in different types of cancer samples [ 13 , 14 ]. HPV types 6, 11, 40, 42, 43, 44, and 54 are considered to be of low oncogenic risk, causing particularly benign lesions, such as genital warts, low-grade intraepithelial squamous lesions, and laryngeal papillomatosis [ 13 , 14 , 15 ].…”

Bioconjugation of AuNPs with HPV 16/18 E6 antibody through physical adsorption technique

“…A positive E6 assay, indicates high correlation to the cervical cancerous phenotype, not the potential for cervical cancer, thus high specificity in triaging patients during screening (6)(7)(8) Nanobiotechnology is being used in cancer diagnostics to enhance detection (11). It uses nanosized tools and systems in the study of biological phenomena for example in prevention (nanovaccines), diagnosis (in vivo and in vitro diagnostics) and in treatment (drug delivery) (12).…”