Research Center, Hellenic Anticancer Institute, Athens, Greece.
Department of Clinical Therapeutics, Alexandra Hospital, National and Kapodistrian University of Athens School of Medicine, Athens, Greece.
Expert Rev Mol Med. 2021 Dec 1;23:e19. doi: 10.1017/erm.2021.18.
Human papillomavirus 16 (HPV16) infection is the aetiologic factor for the development of cervical dysplasia and is regarded as highly carcinogen, because it is implicated in more than 50% of cervical cancer cases, worldwide. The tumourigenic potential of HPV16 has triggered the extensive sequence analysis of viral genome in order to identify nucleotide variations and amino acid substitutions that influence viral oncogenicity and subsequently the initiation and progression of cervical cancer. Nowadays, specific mutations of HPV16 DNA have been associated with an increased risk of high-grade squamous intraepithelial lesions and invasive cervical cancer (ICC) development, including E6: Q14H, H78Y, L83V, Ε7: N29S, S63F, E2: H35Q, P219S, T310K, E5: I65V, whereas highly conserved regions of viral DNA have been extensively characterised. In addition, numerous novel HPV16 mutations are observed among the studied populations from various geographic regions, hence advocating that different HPV16 strains seem to emerge with different tumourigenic capacities. The present review focuses on the variability of the early genes and the long control region, emphasising on the association of specific mutations with the development of severe dysplasia. Finally, it evaluates whether specific regions of HPV16 DNA are able to serve as valuable biomarkers for cervical cancer risk.
人乳头瘤病毒 16 型（HPV16）感染是宫颈发育不良的病因，被认为是高度致癌因素，因为它与全球超过 50%的宫颈癌病例有关。HPV16 的致癌潜能促使对病毒基因组进行广泛的序列分析，以确定影响病毒致癌性的核苷酸变异和氨基酸取代，进而引发宫颈癌的发生和发展。如今，HPV16 DNA 的特定突变与高级别鳞状上皮内病变和浸润性宫颈癌（ICC）的发展风险增加有关，包括 E6：Q14H、H78Y、L83V、E7：N29S、S63F、E2：H35Q、P219S、T310K、E5：I65V，而病毒 DNA 的高度保守区已得到广泛研究。此外，在来自不同地理区域的研究人群中观察到大量 HPV16 新突变，因此不同的 HPV16 株似乎具有不同的致癌能力。本综述重点介绍了早期基因和长控制区的变异性，强调了特定突变与严重发育不良发展的关联。最后，评估了 HPV16 DNA 的特定区域是否能够作为宫颈癌风险的有价值的生物标志物。
