Szostek Slawa, Zawilinska Barbara, Kopec Jolanta, Kosz-Vnenchak Magdalena
Department of Virology, Chair of Microbiology, Jagiellonian University Medical College, Kraków, Poland.
Acta Biochim Pol. 2009;56(2):337-42. Epub 2009 Jun 4.
Cervical carcinogenesis is a complex problem with papillomavirus widely accepted as a causative agent. Integration of a human papillomavirus (HPV) of the high-risk type into the host cell genome is one of the major contributing factors to cervical malignant transformation. In this study, the correlation of CMV, EBV, HSV-1, HSV-2, HHV-6 and HHV-7 infections with the physical status of the HPV genome in cervical cancer and precancerous cervical lesions was investigated in sixty HPV-16-positive women. Cervical secretion samples were submitted to DNA extraction and analyzed by PCR. HPV-16 DNA was confirmed in genotyping with the reverse hybridization line probe assay. Multiplex PCR with specific primers for the E2/E6 genes was used to assess the viral integration status of HPV-16. Our results show that CMV DNA was more frequently present in samples with mixed forms of HPV-16 than in the episomal form (P < 0.025). Such a correlation was also observed in the case of EBV (P < 0.005). The presence of CMV resulted in a six-fold (OR 6.069; 95% CI 1.91-19.22; P = 0.002), while EBV caused a seven-fold (OR 7.11; 95% CI 1.70-29.67; P = 0.007) increase in the risk of the integrated or mixed HPV-16 genome occurrence. Our data suggest that coinfection with herpesviruses, especially CMV and EBV, may be involved in the integration of the HPV-16 genome and may contribute to the development of cervical cancer.
宫颈癌发生是一个复杂的问题，人乳头瘤病毒被广泛认为是一种致病因素。高危型人乳头瘤病毒（HPV）整合到宿主细胞基因组中是宫颈恶性转化的主要促成因素之一。在本研究中，对60名HPV-16阳性女性进行了研究，以调查巨细胞病毒（CMV）、EB病毒（EBV）、单纯疱疹病毒1型（HSV-1）、单纯疱疹病毒2型（HSV-2）、人疱疹病毒6型（HHV-6）和人疱疹病毒7型（HHV-7）感染与宫颈癌及癌前宫颈病变中HPV基因组物理状态的相关性。宫颈分泌物样本进行DNA提取并通过聚合酶链反应（PCR）分析。采用反向杂交线探针法进行基因分型以确认HPV-16 DNA。使用针对E2/E6基因的特异性引物进行多重PCR，以评估HPV-16的病毒整合状态。我们的结果表明，与游离形式相比，CMV DNA在具有混合形式HPV-16的样本中更频繁出现（P < 0.025）。EBV的情况也观察到这种相关性（P < 0.005）。CMV的存在导致整合或混合HPV-16基因组出现风险增加6倍（比值比[OR] 6.069；95%可信区间[CI] 1.91 - 19.22；P = 0.002），而EBV导致风险增加7倍（OR 7.11；95% CI 1.70 - 29.67；P = 0.007）。我们的数据表明，疱疹病毒的合并感染，尤其是CMV和EBV，可能参与HPV-16基因组的整合，并可能促进宫颈癌的发生。
