[Association between high risk human papillomavirus DNA load and cervical lesions in different infection status]

Zhonghua Zhong Liu Za Zhi. 2018 Jun 23;40(6):475-480. doi: 10.3760/cma.j.issn.0253-3766.2018.06.015.
[Article in Chinese]

Abstract

Objective: To explore the relationship between high risk HPV (HR-HPV) DNA load and cervical lesions in HR-HPV single/ multiple infections. Methods: Two thousand six hundred and forty-six women from Shanxi, Henan and Xinjiang were recruited into a cervical cancer screening program. Cervical exfoliated cell specimens collected from all of the participants were detected by hybrid capture Ⅱ (HC2), cytological diagnosis was performed according to the Bethesda System, and pathological diagnosis was interpreted using cervical intraepithelial neoplasia (CIN) terminology.Totally 571 cervical specimens were selected and retested to ascertain the HPV types and single/ multiple infections by liner array, a PCR-based method. Semi-quantitative result of HR-HPV DNA load (pg/ml) was estimated by HR HC2.According to the taxonomy of "International Human Papillomavirus Reference Center" , 13 HR-HPVs, including HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and 68, which could be detected by HR HC2 were divided into 4 subgroups. Results: The positive rate of HR-HPV in normal cervix (436 cases), CIN1 (88 cases), CIN2+ (47 cases) group were 29.82%, 85.23% and 100%, respectively. The overall prevalence and median viral load increased coordinating with the pathological degree of cervical lesions (P<0.001). The positive rate and viral load of single infection with HR-HPV belongs to α9 species increased coordinating with the pathological degree of cervical lesions (P<0.05). The viral load of single infection with HR-HPV belongs to α7 species in CIN1 group was higher than those of normal group and CIN2+ group, but without statistical significance (P=0.130). The viral load of multiple infections in CIN1 group was 559.13 pg/ml, significantly higher than 37.73 pg/ml of normal histology (P=0.025), but without significant difference of 332.91 pg/ml of CIN2+ group (P=0.790). The median viral load of HPV single infection in CIN1 group was 167.93 pg/ml, significantly lower than 559.73 pg/ml of multiple infections (P=0.044). The incidence of co-infection with HR-HPVs belong to α9 species was 80.56%, dominated in all patterns of multiple infections and their median viral load increased coordinating with the pathological degree of cervical lesions, but without significant difference (P>0.05). The incidence of co-infection with HR-HPVs belong to α7 species was 66.67%, their median viral load in CIN1 group was higher than that of CIN2+ group, but without statistical significance (P>0.05). Conclusions: Viral loads of single/ multiple infections with HR-HPVs belong to different species show different tendencies coordinating with the pathological degree of cervical lesions. Women with high grade of cervical lesion were dominantly infected with high viral load of HR-HPVs belong to α9 species, and the viral load of multiple infections is higher than that of single infection in low grade of cervical lesion.

目的: 探讨单一或多重感染状态下高危型人乳头状瘤病毒(HR-HPV)DNA病毒载量与宫颈病变之间的关系。 方法: 在山西省、河南省和新疆维吾尔自治区共招募2 653名参加宫颈癌筛查的女性,采用高危型第二代杂交捕获(HR HC2)技术检测所有参与者的宫颈脱落细胞标本,按照TBS分类系统进行细胞学诊断。571例宫颈标本进行PCR扩增+线性反向杂交HPV分型检测,以确定HPV型别及单一或多重感染;以HR HC2半定量检测结果反映HR-HPV的病毒载量。根据国际人乳头状瘤病毒参照中心中的HPV生物学分类,将HR HC2检测范围内的13种HR-HPV分成不同亚组进行分析。 结果: 正常宫颈组(436例)、宫颈上皮内瘤变1级(CIN1)组(88例)和宫颈上皮内瘤变2级及以上(CIN2+)组(47例)研究对象的HR-HPV阳性率分别为29.82%、85.23%和100%。随着宫颈病变级别的增高,HPV单一感染率及其病毒载量均呈升高趋势(P<0.001)。单一感染中,α-9 HR-HPV阳性率及其病毒载量均随宫颈病变的增高而升高(P<0.05);α-7 HR-HPV的病毒载量在CIN1组较高,但各组病变之间的差异无统计学意义(P=0.130)。多重感染者的中位病毒载量总体趋势为CIN1组(559.13 pg/ml)高于正常组(37.73 pg/ml,P=0.025)和CIN2+组(332.91 pg/ml,P=0.790),而CIN1组单一感染者的中位病毒载量(167.93 pg/ml)低于多重感染(559.73 pg/ml,P=0.044);α-9 HR-HPV多重感染占所有多重感染的80.56%,其病毒载量随病变增高而升高,但各病变级别的病毒载量分布差异无统计学意义(P>0.05);其次为α-7 HR-HPV多重感染(66.67%),其病毒载量在CIN1组中较高,但与CIN2+组比较,差异无统计学意义(P>0.05)。 结论: 不同种系HR-HPV单一或多重感染者的病毒载量随宫颈病变级别的增高呈现出不同的趋势,宫颈高级别病变中以α-9 HR-HPV高病毒载量感染为主,低级别病变中HR-HPV多重感染病毒载量高于单一感染病毒载量。.

Keywords: Cervical lesion; Human papillomavirus; Multiple infections; Single infection; Viral load.

MeSH terms

  • Coinfection / epidemiology
  • Coinfection / virology
  • DNA, Viral / analysis*
  • Early Detection of Cancer
  • Female
  • Human papillomavirus 16
  • Humans
  • Incidence
  • Mass Screening
  • Middle Aged
  • Papillomaviridae / classification
  • Papillomaviridae / isolation & purification*
  • Papillomavirus Infections / diagnosis
  • Polymerase Chain Reaction
  • Prevalence
  • Uterine Cervical Dysplasia / diagnosis
  • Uterine Cervical Dysplasia / pathology
  • Uterine Cervical Dysplasia / virology*
  • Uterine Cervical Neoplasms
  • Viral Load* / genetics

Substances

  • DNA, Viral