人乳头瘤病毒与重要性传播疾病病原体共感染对不同宫颈病变发生风险的影响

Impact of human papillomavirus and important sexually transmitted disease pathogen co-infections on the risk of different cervical lesions

目的高危型人乳头瘤病毒(HR-HPV)的持续感染是鳞状细胞宫颈癌(SCC)发病的首要因素,并且是进展为高级别鳞状上皮内病变(HSIL)的先决条件。一些性传播疾病病原体可能起到人乳头瘤病毒(HPV)共因子的作用。方法选取2017年8月至2018年3月在南京同仁医院参加宫颈癌筛查项目及接受阴道镜检查的420例患者作为研究对象。应用多重聚合酶链式反应技术同时检测淋球菌、阴道毛滴虫、单纯疱疹病毒1型(HSV-1)、单纯疱疹病毒2型(HSV-2)、梅毒螺旋体等在不同宫颈细胞学检查结果中与HPV的共感染率。结果在HR-HPV和淋球菌合并感染的情况下,未明确意义的非典型鳞状上皮细胞及更高级别上皮细胞病变(≥ASC-US)的发生风险增加[相对危险度(RR)3.338,95%置信区间(CI)2.453-4.542,P<0.005],且主要为HSIL(RR 6.242,95%CI 2.901-13.433,P<0.005)。HPV与HSV-2共感染仅表现出发生≥ASC-US的风险增加(RR 3.248,95%CI 2.306-4.575,P<0.005),而不增加发生HSIL的风险(RR 1.639,95%CI 0.260-10.332,P=0.478)。结论淋球菌是与HR-HPV相关的主要病原体,两者共感染提高了所有级别宫颈异常发生的风险,尤其是HSIL。提示其在宫颈病变进展中可能起到与HPV的协同作用。HSV-2与HPV的共感染仅增加了发生≥ASC-US的风险。提示其对于细胞的初始转化是必要条件,但并非SCC进展的必要条件。

Objective Persistent infection of high-risk human papillomavirus(HR-HPV) is the primary cause of squamous cell carcinoma(SCC) and a prerequisite for progression to high-grade squamous intraepithelial lesions(HSIL). Some pathogens of sexually transmitted diseases may be co-factors of human papillomavirus(HPV). Methods A total of 420 cases who underwent in the cervical cancer screening program and received colposcopy were selected in Nanjing Tongren Hospital from August 2017 to March 2018. The co-infection rates of Neisseria gonorrhoeae, Trichomonas vaginalis, herpes simplex virus type 1(HSV-1), herpes simplex virus type 2(HSV-2) and Treponema pallidum with HPV were detected by multiplex polymerase chain reaction. Results In the cases of HR-HPV and Neisseria gonorrhoeae co-infection, the risk of atypical squamous cells of undetermined significance or higher grade lesions(≥ASC-US) was increased [relative risk(RR) 3.338, 95% confidence interval(CI) 2.453-4.542, P<0.005], mainly HSIL(RR 6.242, 95%CI 2.901-13.433, P<0.005). In the cases of HPV and HSV-2 co-infection, there was an increased risk of ≥ASC-US(RR 3.248, 95%CI 2.306-4.575, P<0.005), and no increased risk of HSIL(RR 1.639, 95%CI 0.260-10.332, P=0.478). Conclusions Neisseria gonorrhoeae is the main pathogen associated with HR-HPV. Their co-infection increases the risk of cervical abnormalities at all levels, especially HSIL, suggesting that Neisseria gonorrhoeae may be a co-factor with HPV in the progression of cervical lesions. The co-infection of HSV-2 and HPV only increases the risk of ≥ASC-US, suggesting that HSV-2 is necessary for initial cell transformation, but not necessary for SCC progression.