de Oliveira Maylla Cardoso, de Oliveira Janaina Nicolau, Castilha Eliza Pizarro, Fortunato Giulia Mariane, da Silva Pamella Rodrigues, Pacheco Bianca Lisley Barboza, Couto-Filho José d'Oliveira, Guembarovski Roberta Losi, Brajão de Oliveira Karen
Laboratory of Molecular Genetics and Immunology, Department of Immunology, Parasitology and General Pathology, Center of Biological Sciences, State University of Londrina, Londrina 86057-970, PR, Brazil.
Cancer Hospital of Londrina, Londrina 86015-520, PR, Brazil.
Viruses. 2025 Mar 21;17(4):453. doi: 10.3390/v17040453.
High-risk Human Papillomavirus (HPV) infection is the main etiological factor for cervical carcinogenesis, although genetic cofactors also play a role. Single-nucleotide variants (SNVs) in the gene can alter the gene expression and immune response against HPV, influencing cervical malignancy progression. This study analyzed the association of the alleles, genotypes, and haplotypes of the SNVs rs5742909 (-318 C>T), rs231775 (+49 A>G), and rs3087243 (+6230 G>A) with HPV infection, the development of low-grade squamous intraepithelial lesions (LSILs), high-grade squamous intraepithelial lesions (HSILs), and cervical cancer in 445 women treated by the public health service of Paraná, Brazil. Peripheral blood and cervical secretion samples were collected for genomic DNA extraction, SNV genotyping, and HPV detection via PCR. Statistical analyses used < 0.05. The HPV-negative control group included 181 women, while the HPV-positive group included 264 women. The HPV-positive group was divided into no lesion (n = 84), LSILs (n = 19), HSILs (n = 56), and cervical cancer (n = 105). The T allele of -318 C>T and the TAG haplotype were associated with increased susceptibility to HPV infection, HSILs, and cervical cancer. These findings suggest that the T allele of -318 C>T and the TAG haplotype may serve as potential molecular biomarkers for HPV susceptibility and worse prognosis.
高危型人乳头瘤病毒（HPV）感染是宫颈癌发生的主要病因，尽管遗传辅助因素也起一定作用。该基因中的单核苷酸变异（SNV）可改变基因表达以及针对HPV的免疫反应，影响宫颈癌的进展。本研究分析了SNV rs5742909（-318 C>T）、rs231775（+49 A>G）和rs3087243（+6230 G>A）的等位基因、基因型和单倍型与HPV感染、低级别鳞状上皮内病变（LSIL）、高级别鳞状上皮内病变（HSIL）以及宫颈癌发生的相关性，研究对象为巴西巴拉那州公共卫生服务机构治疗的445名女性。采集外周血和宫颈分泌物样本用于基因组DNA提取、SNV基因分型以及通过聚合酶链反应（PCR）检测HPV。统计分析采用的P值<0.05。HPV阴性对照组包括181名女性，HPV阳性组包括264名女性。HPV阳性组又分为无病变（n = 84）、LSIL（n = 19）、HSIL（n = 56）和宫颈癌（n = 105）。-318 C>T的T等位基因以及TAG单倍型与HPV感染、HSIL和宫颈癌的易感性增加相关。这些发现表明，-318 C>T的T等位基因和TAG单倍型可能作为HPV易感性及预后较差的潜在分子生物标志物。
