Department of Biological and Biomedical Sciences, North Carolina Central University, Durham, North Carolina.
Department of Epidemiology, UNC Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina.
J Med Virol. 2019 Mar;91(3):450-456. doi: 10.1002/jmv.25336. Epub 2018 Oct 31.
Human papillomavirus (HPV) infection is known to contribute to cervical carcinogenesis, yet other cofactors that may contribute to oncogenesis are poorly understood. Herein, we examine whether the Epstein-Barr virus (EBV) and human cytomegalovirus (CMV), two oncomodulatory viruses, are associated with HPV-mediated cervical neoplastic progression.
Sixty patient cervical brush samples from a study of North Carolina women were obtained. HPV RNA positivity was determined by Aptima testing (Hologic Corporation, Marlborough, MA). The level of viral transcripts for EBV and CMV was quantified (reverse transcription polymerase chain reaction analysis), and the coinfection status with HPV was then compared with the patient's cervical cytology grade.
Over one-third (38.3%) of the study population was CMV positive, whereas 43.3% was EBV positive. When sample data were stratified by the cytology grade, 36.5% (19/52) of normal patients, 75% (3/4) of low-grade squamous intraepithelial lesions (LSIL), and 100% (4/4) of patients with high-grade SIL (HSIL) were EBV positive. Conversely, 35.2% (18/52) of normal patients, 25% (1/4) of patients with LSIL, and 50% (2/4) of patients with HSIL were CMV positive. When examining only HPV positive-associated HSIL, 100% (4/4) were positive for both HPV and EBV detection. This suggests that co-viral detection with HPV and EBV is associated with more advanced HSIL cervical lesions, while CMV displayed no clear association with a higher grade of cervical cytology.
Co-viral detection with EBV may increase the oncogenicity and/or serve as a viral marker of progression to HPV-associated high-grade cervical dysplasia.
人乳头瘤病毒(HPV)感染已知会导致宫颈癌的发生,但其他可能促进癌变的协同因子则知之甚少。在此,我们研究了爱泼斯坦-巴尔病毒(EBV)和人类巨细胞病毒(CMV)这两种致癌调节病毒是否与 HPV 介导的宫颈肿瘤进展有关。
从北卡罗来纳州妇女的一项研究中获得了 60 例患者宫颈刷样本。通过 Aptima 检测(豪洛捷公司,马萨诸塞州马尔伯勒)确定 HPV RNA 阳性。通过逆转录聚合酶链反应分析(RT-PCR)定量检测 EBV 和 CMV 的病毒转录本,并将 HPV 感染的合并感染状况与患者的宫颈细胞学分级进行比较。
研究人群中有三分之一以上(38.3%)为 CMV 阳性,而 43.3%为 EBV 阳性。当按细胞学分级对样本数据进行分层时,36.5%(19/52)的正常患者、75%(3/4)的低级别鳞状上皮内病变(LSIL)和 100%(4/4)的高级别 SIL(HSIL)患者 EBV 阳性。相反,35.2%(18/52)的正常患者、25%(1/4)的 LSIL 患者和 50%(2/4)的 HSIL 患者 CMV 阳性。当仅检查与 HPV 阳性相关的 HSIL 时,100%(4/4)的患者同时检测到 HPV 和 EBV 阳性。这表明 HPV 和 EBV 的共病毒检测与更高级别的 HSIL 宫颈病变相关,而 CMV 与更高级别的宫颈细胞学无明显关联。
与 EBV 的共病毒检测可能增加 HPV 相关高级别宫颈发育不良的致癌性和/或作为病毒进展标志物。