应用液相基因芯片技术筛查山东地区高危人群人乳头瘤病毒基因型

目的 评价Luminex XMAP系统的液相芯片技术在女性生殖道人乳头状瘤病毒（HPV）感染检测中的临床价值,调查山东地区女性生殖道HPV感染情况及最常见的基因型。方法 取妇科门诊就诊者宫颈脱落细胞2925例,采用液相芯片技术进行HPV基因型检测,96孔板操作,26种亚型1次呈现。639例患者同时做病理诊断,按组织病理学分为细胞学正常组、炎症组、宫颈上皮内瘤变（CIN）Ⅰ组、CINⅠ-Ⅱ组、CINⅡ组、CINⅢ组和宫颈癌组。通过HPV DNA亚型分布结合病理诊断,分析山东地区HPV感染基因型与宫颈病变程度的关系。结果 HPV总感染率36．0% （1054/2925）,26种基因型检出23种,按感染率从高到低依次为HPV-16（26．75%）,HPV-52 （25．75%）,HPV-58（10．47%）,HPV-18（8．87%）和HPV-11（6．94%）。其中高危型感染占87．32%,低危型13．68%;单一型感染698例（66．22%）,多重感染356例（33．78%）,低危亚型11、6多与高危型多重感染。1054例HPV阳性患者中,261例（24．8%）为21～25岁女性,随年龄增大阳性例数减少, 52例（4．9％）为51～67岁女性。各病理组HPV阳性率及多重感染率依次为正常组23．37％、4．89％，炎症组33．08％、7．14％，CINI组54．54％、18．18％，CINⅠ-Ⅱ组57．14％、28．57％，CIN Ⅱ组82．61％、41．30％，CINⅢ组91．30％、43．37％，宫颈癌组100％、38．46％。以组织病理学为确诊标准，液相芯片HPVDNA检测CINⅡ、Ⅲ和宫颈癌的灵敏度、特异度、阳性预测值、阴性预测值依次为88．57％、76．63％、68.89％和92．16％。结论 所选山东地区高危人群HPV感染的常见基因型是16、52、58、18、11、6、56、31。随宫颈病变程度加重，HPV感染率及多重感染有增加趋势，HPV阳性以年轻女性多见。液相芯片HPVDNA检测在宫颈病变临床诊断及大规模筛查中有重要价值。

Study on the genotyping of human papillomavirus using a new DNA liquid chip in women of high-risk group of Shandong province

OBJECTIVE: To evaluate the diagnostic applicability of human papillomavirus (HPV) liquid chip assay which is based on Luminex XMAP System, and perform a HPV epidemiologic study with the liquid chip in women of Shandong province. METHODS: To detect HPV genotypes on a 96-well plate with the liquid chip which can simultaneously detect and identify 26 common HPV genotypes in a total of 2925 cervical scrapes obtained from gynecological outpatients as well as to analyze the relationship between HPV types and different cervical diseases by studying the distribution of HPV genotypes and pathologic diagnosis. RESULTS: Among 639 cases who performed pathologic/cytological and histological diagnoses, 184 cases are in group of normal cytology, 266 cases in group of, 77 cases in group of cervical intra-epithelial neoplasia (CIN) I, 7 cases in group of CIN I - II, 46 cases in group of CIN I - II, 46 cases in group of CIN I - II and 13 cases in group of cervical cancer. The overall incidence of HPV in our samples is 36.0% (1054/2925) and 23 types of all 26 types on liquid chip are found. The most common genotypes found are HPV-16 (26.75%), HPV-52 (25.75%), HPV-58 (10.47%), HPV-18 (8.87%) and HPV-11 (6.94%). Among all the positive types, 87.32% are high-risk HPV and 13.68% are low-risk HPV genotypes. Both single and multiple types are easily identified, showing 66.22% ( n = 698) single type and 33.78% ( n = 356) multiple types. Of all the 1054 HPV-positive cases, 261 (24.8%) is occupied by women 21 to 25 years of age and progressively lower by older age groups, reaching 4.9% by women between 51 to 67 years old. The incidence of HPV in our samples is 23.37%, 33.08%, 54.54%, 57.14%, 82.61%, 91.30% and 100% for normal cytology, inflammation,CIN I ,CIN I - II, CIN II ,CIN III, and carcinomas specimens, respectively. Infections with more that one virus are common, accounted for 4.89%, 7.14%, 18.18%, 28.57%, 41.30%, 43.37% and 38.46% for normal cytology, inflammation, CIN I, CIN I - II, CIN II, CIN III, and carcinomas specimens, respectively. Based on the criteria of histology and pathology, the sensitivity, specificity, positive-predictive value and negative-predictive value of HPV liquid chip assay for detecting all cases of CIN II, III are 88.57%, 76.63%, 68.89% and 92.16% respectively. Conclusion The common types of HPV infection are 16, 52, 58, 18, 11, 6, 56 and 31. The HPV-positive rate increased along with the increase of grading on cervical lesions. There are more younger women among all the HPV-positive ones. Multiplex HPV genotyping by liquid chip appears to be highly suitable for diagnostic screening as well as the conduction of large-scale epidemiological studies.