Abstract
Persistent infection with the human papillomavirus 16 (HPV 16) is the cause of half of all cervical carcinomas (CC) cases. Moreover, mutations in the oncoproteins E6 and E7 are associated with CC development. In this study, E6/E7 variants circulating in southern Mexico and their association with CC and its precursor lesions were evaluated. In total, 190 DNA samples were obtained from scrapes and cervical biopsies of women with HPV 16 out of which 61 are from patients with CC, 6 from patients with high-grade squamous intraepithelial lesions (HSIL), 68 from patients with low-grade squamous intraepithelial lesions (LSIL), and 55 from patients without intraepithelial lesions. For all E7 variants found, the E7-C732/C789/G795 variant (with three silent mutations) was associated with the highest risk of CC (odd ratio (OR) = 3.79, 95% confidence interval (CI) = 1.46–9.85). The analysis of E6/E7 bicistron conferred to AA-a*E7-C732/C789/G795 variants revealed the greatest increased risk of CC (OR = 110, 95% CI = 6.04–2001.3), followed by AA-c*E7-C732/C789/G795 and A176/G350*E7-p. These results highlight the importance of analyzing the combinations of E6/E7 variants in HPV 16 infection and suggest that AA-a*E7-C732/C789/G795, AA-c*E7-C732/C789/G795, and A176/G350*E7-p can be useful markers for predicting CC development.
Highlights
Persistent infection with high-risk human papillomavirus (HR-HPV) is the main cause of cervical carcinoma (CC) and its precursor lesions [1]
We have previously reported that the most frequent E6 variants of human papillomavirus 16 (HPV 16) and those associated with a high risk of developing CC were the European A1 and A2 sublineages (E-G350, E-prototype, E-A176/G350, and E-C188/G350) and Asian-American D2 (AA-a and AA-c) lineages [21]
This is the first study of E7 variants in HPV 16 in Mexico involving the analyses of variant combinations in the HPV E6/E7 bicistron in cervical samples as well as their association with the development of CC and its precursor lesions
Summary
Persistent infection with high-risk human papillomavirus (HR-HPV) is the main cause of cervical carcinoma (CC) and its precursor lesions [1]. Among the HR-HPV types, HPV causes more than half of CC cases worldwide [2,3]. The oncogenicity of HPV 16 is because of the oncoproteins E6 and E7, which promotes cell transformation and immortalization; increase cell proliferation; invasion and migration; and supports immune evasion. E7 binds to retinoblastoma proteins p107 and p130 and causes immortalization and deregulation of cell proliferation and differentiation. These oncoproteins act together to promote cervical carcinogenesis [4,5,6]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
