Department of Clinical Analysis and Biomedicine, State University of Maringá, Av, Colombo 5790, Maringá 87020-900, Paraná, Brazil.
Infect Agent Cancer. 2013 Oct 7;8(1):38. doi: 10.1186/1750-9378-8-38.
Human Papillomavirus (HPV) infection is a serious problem for human immunodeficiency virus (HIV)-infected women, increases their risk of cervical lesions and cancer. In cervical carcinogenesis, mutations in the p53 gene occur most frequently within exons 5-8. To our knowledge, no previous studies have analyzed mutations in exons 5-8 of the p53 gene in HIV- and HPV-infected women. In our study, we verified these mutations in women with and without cervical abnormalities.
The study included 160 women, divided into three groups: (1) 83 HPV- and HIV-infected women (HIV group); (2) 37 HPV-infected/HIV-uninfected (control group); and (3) 40 normal cytology/DNA-HPV negative/HIV-uninfected women (negative control p53 reactions). HPV-DNA was detected using polymerase chain reaction (PCR) and genotyping by PCR-restriction fragment length polymorphism analysis. Using primers for exons 5-8, the mutation of the p53 gene was verified by PCR-single strand conformational polymorphism. The total mutation of the p53 gene in exons 5-8 was not significantly associated with the HIV and control groups. The mutations in exon 7 were the highest in the HIV group (43.8%) and in exon 6 in the control group (57.2%) (p = 0.0793) suggesting a tendency toward differential mutation in exon 7 in the HIV group.
Our study provides preliminary evidence that the mutation in exon 7 might be an important differentiating factor for cervical carcinogenesis in HIV-infected women. This aspect deserves an additional cross-sectional and longitudinal study using a larger sample size with a higher number of High-grade squamous intraephitelial lesion (HSIL) to observe the evolution of cervical lesions.
人乳头瘤病毒（HPV）感染是人类免疫缺陷病毒（HIV）感染妇女的一个严重问题，增加了她们宫颈病变和癌症的风险。在宫颈癌的发生过程中，p53 基因的突变最常发生在外显子 5-8 内。据我们所知，以前没有研究分析过 HIV 和 HPV 感染妇女的 p53 基因外显子 5-8 的突变。在我们的研究中，我们在有和没有宫颈异常的妇女中验证了这些突变。
该研究纳入了 160 名女性，分为三组：（1）83 名 HPV 和 HIV 感染的女性（HIV 组）；（2）37 名 HPV 感染/无 HIV 感染的女性（对照组）；和（3）40 名正常细胞学/HPV-DNA 阴性/无 HIV 感染的女性（p53 反应阴性对照组）。采用聚合酶链反应（PCR）检测 HPV-DNA，采用 PCR-限制性片段长度多态性分析进行基因分型。使用外显子 5-8 的引物，通过 PCR-单链构象多态性验证 p53 基因的突变。外显子 5-8 中 p53 基因的总突变与 HIV 组和对照组均无显著相关性。外显子 7 的突变在 HIV 组最高（43.8%），在外显子 6 中在对照组最高（57.2%）（p=0.0793），提示 HIV 组外显子 7 的突变有差异的趋势。
本研究初步表明，外显子 7 的突变可能是 HIV 感染妇女宫颈癌发生的一个重要鉴别因素。这方面值得进一步进行横断面和纵向研究，使用更大的样本量和更高比例的高级别鳞状上皮内病变（HSIL）来观察宫颈病变的演变。
