Genetic variability and functional implication of HPV16 from cervical intraepithelial neoplasia in Shanghai women.

Human papillomavirus (HPV)16 gene mutation is usually associated with persistent HPV infection and cervical intraepithelial neoplasia (CIN). However, the functional implications of HPV16 mutations remain poorly understood.145 LCR/E6/E7 of the HPV16 isolates were amplified and sequenced, and HPV16 integration status was detected. In total, 89 SNPs (68 in the LCR, 13 in E6, 8 in E7) were discovered, 11 of which were nonsynonymous mutations (8 in E6, 3 in E7). The H85Y and E120D variants in E6 were significantly reduced in the high-grade squamous intraepithelial lesion (HSIL) group compared to the <HSIL group (P = .046 and .005), conversely the N29S in E7(P = .01). Amino acid substitutions (D32N/E, E36Q, H85Y, and E120D in E6 and N29H/S and R77C in E7) were predicted to have an effect on conserved structural and functional residues, and five amino acid substitutions (H85Y, E36Q, I34L, and D32E in E6; R77C in E7) would potentially change the secondary structure. "6329G>T," a potential binding site for TATA-binding protein, is the most common in LCR variants. A4 (Asian) was associated with an increased risk of HSIL compared to A1-3(P = .009). The H85/E120 in E6 and N29 in HPV16 E7 might play a critical role in carcinogenesis by disrupting p53 and Rb degradation due to affecting their interaction, respectively. In a word, the findings in this study provide preventative and therapeutic interventions of HPV16 -related cervical lesions/cancer.

Zhao J ，Zhu J ，Guo J ，Zhu T ，Zhong J ，Liu M ，Ruan Y ，Liao S ，Li F ... -  《-》

Association between human papillomavirus type 16 E6 and E7 variants with subsequent persistent infection and recurrence of cervical high-grade squamous intraepithelial lesion after conization.

The study aimed to detect the variants of human papillomavirus (HPV) type 16 E6 and E7 in patients with cervical high-grade squamous intraepithelial lesion (HSIL), and to determine the existence and recurrence of persistent infection after treatment with loop electrosurgical excision procedure (LEEP). Preoperatively collected cervical exfoliated cells from 100 HPV 16 positive HSIL patients enrolled in the study were used to test for E6 and E7 variants. Follow-ups which included TCT, HPV test, and colposcopy were performed every 3 months after the operation, and colposcopic biopsy and endocervical curettage were performed for patients with abnormalities. Patients were followed for 2 years, and recurrence was defined as detecting low-grade squamous intraepithelial lesion (LSIL) or relapse of HSIL in 1 year. In 81% of patients, the E6 variant was the Asian prototype (As.P), 14% of patients had the European variant, 2% had the European prototype (EP), and 3% had the African 1 variant (Af1). The HPV16 could be easily cleared by LEEP in patients with As.P. Persistent infection or recurrence was very rare in this group. The patients with European variants T350G or A442C had a significantly higher incidence of persistent and recurring HPV16 infection. In conclusion, (i) in most cases, As.P caused HSIL. (ii) The European variant E6 T350G/A442C may be associated with higher rates of recurring and persistent HPV16 infection after the LEEP. (iii) The E7 gene mutation may not be a risk factor for recurring HSIL caused by HPV16 or persistent infection. J. Med. Virol. 88:1982-1988, 2016. © 2016 Wiley Periodicals, Inc.

Zhang L ，Yang B ，Zhang A ，Zhou A ，Yuan J ，Wang Y ，Sun L ，Cao H ，Wang J ，Zheng W ... -  《-》

Correlation of E6 and E7 levels in high-risk HPV16 type cervical lesions with CCL20 and Langerhans cells.

Jiang B ，Xue M 《Genetics and Molecular Research》

Diagnostic Utility of HPV16 E6 mRNA or E7 mRNA Quantitative Expression for Cervical Cells of Patients with Dysplasia and Carcinoma.

Wu MZ ，Li WN ，Cha N ，Tian LX ，Zhang YI ，Wu X ，Guo KJ ，Wu GP ... -  《-》

Genetic variation in the E6 and E7 genes of human papillomavirus type 16 in northeastern Argentina.

The province of Misiones is considered a region with a high mortality rate due to cervical cancer (CC). To gain insight into this problem, we explored the association between genetic variation in the E6 and E7 oncogenes of HPV16 and the risk of CC. We studied 160 women with cytological diagnoses of negative for intraepithelial lesion or malignity, low-grade squamous intraepithelial lesion, and high-grade squamous intraepithelial lesion/CC and a positive test for HPV16 infection. The genetic characterization of E6 and E7 genes was undertaken through PCR amplification and direct Sanger sequencing. Phylogenetic classification was conducted using Bayesian methods. To estimate the odds ratio (OR) for an association between genetic variants in the E6 and E7 genes and the risk of CC, we used ordinal logistic regression adjusted by age. The final data set comprised 112 samples. Diagnostic single-nucleotide polymorphisms (SNPs) and phylogenetic trees confirmed the presence of Lineage A (95.5%) and D (4.5%) in the samples. For the E6 gene, we identified eleven different sequences, with the most common ones being Lineage A E6 350G (58.9%) and E6 350T (37.5%). The E6 350G was associated with progression to HSIL/CC, with an OR of 19.41 (4.95-76.10). The E7 gene was more conserved than E6, probably due to the functional constraints of this small protein. Our results confirmed the association of the E6 350G SNP with a higher risk of developing CC. These data will contribute to understanding the biological bases of CC incidence in this region.

Totaro ME ，Gili JA ，Liotta DJ ，Schurr TG ，Picconi MA ，Badano I ... -  《-》