国产HPV杂交捕获技术在农村宫颈癌筛查中的应用

Application of domestic HPV hybrid capture test for cervical cancer screening in rural areas of China

目的 人乳头瘤病毒（human papillomavirus,HPV）检测是国内外公认的宫颈癌筛查有效方式。近年来,我国研发了低成本、快速、简单的HPV检测方法,为HPV检测应用到人群筛查提供了希望。本研究分析国产HPV杂交捕获技术（daltonbio hybrid capture 2,DH2）初筛不分流及DH2初筛HPV16/18分型检测分流检出宫颈癌前病变与宫颈癌的情况,评价此种检测技术应用于农村地区宫颈癌筛查的可行性。方法 按整群抽样的方法,对新密市7个乡镇35～64岁的农村妇女使用DH2检测进行宫颈癌筛查,阳性者召回做阴道镜,对镜下发现的可疑病变取活组织检查,病理诊断作为金标准,宫颈上皮内瘤变（cervical intraepithelial neoplasia,CIN）≥2级（CIN2＋）患者需手术治疗。对DH2阳性者同时进行HPV16/18分型检测,探索DH2初筛和HPV16/18分型检测分流策略对宫颈疾病的检出情况。结果DH2筛查阳性率为12.23%（1 512/12 358）,其中≥50岁组HPV感染率和〈50岁组HPV感染率分别为13.40%（749/5 588）和11.27%（763/6 770）,比值比（odds ratio,OR）=1.22（1.09～1.36）,差异有统计学意义,χ^2=12.98,P〈0.001。共检出CIN2＋87例（0.72%）,CIN3＋50例（0.41%）,达到新密市近年最高水平。采用HPV16/18分型检测分流策略的阳性率为2.66%（319/11 981）,检出CIN2＋62例（0.52%）,CIN3＋37例（0.31%）。HPV16/18分流检出CIN2＋占总病例的73.81%（62/84）,检出CIN3＋占总病例的77.08%（37/48）。结论 DH2检测对宫颈癌前病变及宫颈癌的检出率较高,可作为宫颈癌筛查方法使用。HPV16/18分流策略虽然可以降低阴道镜转诊率,但是会漏诊部分CIN2＋患者,漏诊患者的基因型别有待进一步分析。

OBJECTIVE As we all know, human papillomavirus test is an effective method to detect cervical cancer. In recent years, we have developed several screening tests that were rapid, simple and affordable. This provides hope for the application of HPV detection test to women in China. Our study is to analyze the detection rate of precancerous lesions due to uterine cervix and cervical cancer using HPV hybrid capture （DH2） and 16/18 type detection test. METHODS Women aged 35-64 from 7 counties in Xinmi received cervical cancer screening with DH2 test. Colposcope was conducted on DH2 test-positive women, and pathology-confirmed biopsies were done for final diagnosis. Surgery was necessary for women getting pathological results above CIN2 （CIN2 ＋）. H PV16/18 types detection test was also conducted on DH2 test-positive women in order to know the detection rate of precancerous lesions of uterine cervix and cervical cancer when HPV16/18 testing as a triage test. RESULTS The overall HPV positive rate was 12.23%（1 512/12 358）. The positive rate in women over 50 years old was found to be higher than that in women below 50 years old, reached 13.40% （749/5 588） and 11.27%（763/6 770）, odds ratio was 1.22（1.09-1.36）. There was statistical significance of differences in HPV prevalence between populations in different age groups（χ^2 = 12.98 ,P〈0. 001）. The detection number（rate） of CIN2＋ and CIN3＋ were 87（0.72%） and 50（0.41%）, respectively. It reached the highest rate in Xinmi over the latest years. The positive rate of women who were screened with HPV16/18 types detection test was 2.66% （319/11 981）. HPV16/18 was performed as a triage testing that could detect 62 cases of CIN2＋ （0. 52%） and 37 cases of CIN3＋ （0. 31%）, and could detect 73.81%（62/84） CIN2＋ and 77.08%（37/48） CIN3＋ from all cases. CONCLUSIONS The detection rate of precancerous lesions of uterine cervix and cervical cancer was high with DH2 test. We can use DN2 test as one of primary cervical cancer screening methods. Although HPV16/18 detection testing as a triage test decreased the colposcopy referral,it failed to detect part of the CIN2＋ cases. As a result, for the undetected CIN2＋ cases, the HPV genotyping is needed for future analysis.