Genetics Program, National Cancer Institute José de Alencar Gomes da Silva, Brazil.
Gynecologic Oncology Department, Cancer Hospital II, National Cancer Institute José de Alencar Gomes da Silva, Brazil.
J Med Virol. 2016 Jul;88(7):1279-87. doi: 10.1002/jmv.24458. Epub 2016 Jan 12.
Cervical cancer is the fourth most common cancer among women, and ∼70-80% of these cancers are associated with two human papillomavirus types: HPV16 and HPV18. Several studies have reported that intra-type diversity is associated with the progression of infection to invasive cancer. Herein, we report the genetic diversity of HPV16 and HPV18 in a cohort of 594 Brazilian women with invasive cervical cancer and describe the prevalence of lineages and intra-type diversity prior to the implementation of the public immunization program in Brazil. HPV detection and genotyping were performed using PCR, PGMY/GP primers, and DNA extracted from fresh tumors. The HPV16 (378 women) and HPV18 (80 women) lineages were identified by PCR and sequencing of the LCR and E6 fragments, followed by SNV comparison and phylogenetic analysis. In our cohort, was found a higher frequency of the lineage A (in 217 women), followed by lineage D (in 97 women) and lineages B and C (in 10 women each) for HPV16; and a higher frequency of lineage A (in 56 women) followed by lineage B (in 15 women) in HPV18. The genetic diversity of HPV16 indicated a recent expansion of specific variants or a selective advantage that is associated with invasive cancer; this pattern was not observed for HPV18.
宫颈癌是女性中第四常见的癌症,其中约 70-80%与两种人乳头瘤病毒(HPV)类型有关:HPV16 和 HPV18。多项研究报告称,同型内多样性与感染向浸润性癌症的进展有关。在此,我们报告了巴西 594 名浸润性宫颈癌女性队列中 HPV16 和 HPV18 的遗传多样性,并描述了在巴西实施公共免疫接种计划之前,谱系和同型内多样性的流行情况。HPV 的检测和基因分型采用聚合酶链反应(PCR)、PGMY/GP 引物和从新鲜肿瘤中提取的 DNA 进行。通过对 LCR 和 E6 片段进行 PCR 和测序,随后进行 SNV 比较和系统发育分析,确定 HPV16 和 HPV18 的谱系。在我们的队列中,HPV16 中发现了更高频率的谱系 A(217 名女性),其次是谱系 D(97 名女性)和谱系 B 和 C(各 10 名女性);HPV18 中发现了更高频率的谱系 A(56 名女性),其次是谱系 B(15 名女性)。HPV16 的遗传多样性表明特定变体的近期扩张或与浸润性癌症相关的选择性优势;HPV18 中没有观察到这种模式。