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However, the functional implications of HPV16 mutations remain poorly understood.145 <jats:italic>LCR<\/jats:italic>\/<jats:italic>E6<\/jats:italic>\/<jats:italic>E7<\/jats:italic> of the HPV16 isolates were amplified and sequenced, and HPV16 integration status was detected. In total, 89 SNPs (68 in the <jats:italic>LCR<\/jats:italic>, 13 in <jats:italic>E6<\/jats:italic>, 8 in <jats:italic>E7<\/jats:italic>) were discovered, 11 of which were nonsynonymous mutations (8 in <jats:italic>E6<\/jats:italic>, 3 in <jats:italic>E7<\/jats:italic>). The H85Y and E120D variants in E6 were significantly reduced in the high\u2010grade squamous intraepithelial lesion (HSIL) group compared to the &lt;HSIL group (<jats:italic>P\u2009<\/jats:italic>=\u2009.046 and .005), conversely the N29S in E7(<jats:italic>P\u2009<\/jats:italic>=\u2009.01). 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. \u201c6329G&gt;T,\u201d a potential binding site for TATA\u2010binding protein, is the most common in <jats:italic>LCR<\/jats:italic> variants. A4 (Asian) was associated with an increased risk of HSIL compared to A1\u20133(<jats:italic>P\u2009<\/jats:italic>=\u2009.009). 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 \u2010related cervical lesions\/cancer.<\/jats:p>","DOI":"10.1002\/jmv.25618","type":"journal-article","created":{"date-parts":[[2019,10,31]],"date-time":"2019-10-31T11:39:33Z","timestamp":1572521973000},"page":"372-381","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Genetic variability and functional implication of HPV16 from cervical intraepithelial neoplasia in Shanghai women"],"prefix":"10.1002","volume":"92","author":[{"given":"Junwei","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, East Hospital Tongji University School of Medicine Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiacheng","family":"Zhu","sequence":"additional","affiliation":[{"name":"BGI Education Center University of Chinese Academy of Sciences Shenzhen 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