Department of General Surgery and Medical Surgical Specialties, Gynecological Clinic of the University of Catania. Policlinico, Via Santa Sofia 78, 95124, Catania, Italy.
Virol J. 2018 Mar 27;15(1):52. doi: 10.1186/s12985-018-0957-z.
Clinical management of HPV positive women is difficult since many of the infections, including high-risk oncogene genotypes (hr-HPV), are transient. Therefore only a limited number of patients have a high-grade lesion and sending all HPV positive women for colposcopy would only increase costs and unnecessary treatment, with serious psychological consequences for patients. The need has emerged to identify other HPV related markers able to correctly detect women with a high-risk of developing high-grade lesions. Genotyping and the search for E6/E7 mRNA are among the possible candidates.
The study was carried out by means of an observational analysis of the data relative to 674 HR-HPV positive women who we had observed from January 2013 to June 2015; the data had been gathered in a database at the HPV Center of the University Hospital of Catania, Italy. Women were considered eligible for this study if the following data was present in the database: Pap TEST, histologic evaluation, HPV TEST and E6/E7 mRNA detection. We calculated the Odds Ratio (OR) of woman who were mRNA positive, with CIN2+ lesions, and Odds Ratio of HPV16 positive women.
Transcripts were detected in 23.6% (69/292) of the women with CIN1 and in 97.2% (210/220) of those with CIN2 + . Regarding genotyping, the 81,8% (180/220) of the women with CIN2+ had genotype 16, while only 18.1% (40/220) had genotype 18, 31, 33, 45. We calculated the OR in the group of HPV16 women with CIN2+ (OR = 4.62; 95% CI = 3.13 to 6.82), this value increased (OR = 106.12; 95% CI = 53.71 to 209.69) in women with CIN2+ and positive mRNA.
The presence of the HPV16 genotype in our study was associated with a risk 5 times greater of developing a high-grade lesion (CIN2+) (OR = 4.62 95% CI:3.13-6.82); this supports the hypothesis that it would be opportune to have targeted protocols for the management of HPV 16 positive women. The results showed that there was an association between E6/E7 mRNA expression and histology (OR = 106.12; 95% CI = 53.71 to 209.69). The E6/E7 mRNA test showed a higher prevalence of E6 and E7 transcripts in patients with higher-grade lesions.
The results of this study suggest that the HPV genotype determination and E6/E7 mRNA detection would find an important application for management of HPV positive women.
HPV 阳性女性的临床管理较为困难,因为许多感染,包括高危致癌基因型(hr-HPV),都是一过性的。因此,只有少数患者存在高级别病变,对所有 HPV 阳性女性进行阴道镜检查只会增加成本和不必要的治疗,对患者造成严重的心理后果。因此,有必要寻找其他 HPV 相关标志物,以便正确检测出发生高级别病变风险较高的女性。基因分型和 E6/E7 mRNA 检测就是可能的候选方法之一。
该研究通过对 2013 年 1 月至 2015 年 6 月期间观察到的 674 例 HR-HPV 阳性女性的数据分析进行了观察性分析;这些数据是在意大利卡塔尼亚大学医院 HPV 中心的数据库中收集的。如果数据库中存在以下数据,则认为女性符合本研究条件:巴氏试验、组织学评估、HPV 检测和 E6/E7 mRNA 检测。我们计算了 mRNA 阳性、CIN2+病变和 HPV16 阳性女性的比值比(OR)。
CIN1 组中有 23.6%(69/292)的女性检测到转录本,CIN2+组中有 97.2%(210/220)的女性检测到转录本。关于基因分型,CIN2+组中 81.8%(180/220)的女性为 16 型,而只有 18.1%(40/220)的女性为 18 型、31 型、33 型、45 型。我们计算了 HPV16 阳性、CIN2+女性的比值比(OR=4.62;95%CI=3.13 至 6.82),在 CIN2+和 mRNA 阳性的女性中,该值增加(OR=106.12;95%CI=53.71 至 209.69)。
本研究中 HPV16 基因型的存在与发生高级别病变(CIN2+)的风险增加 5 倍相关(OR=4.62 95%CI:3.13-6.82);这支持了对 HPV16 阳性女性进行靶向治疗管理的假说。结果表明,E6/E7 mRNA 表达与组织学之间存在关联(OR=106.12;95%CI=53.71 至 209.69)。E6/E7 mRNA 检测显示,高级别病变患者中 E6 和 E7 转录本的发生率更高。
本研究结果表明,HPV 基因型测定和 E6/E7 mRNA 检测将为 HPV 阳性女性的管理提供重要应用。