阴道自取样HPV宫颈癌筛查联合宫颈细胞学p16~(INK4a)蛋白检测在精准筛查中的应用
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摘要
目的探讨阴道自取样人乳头瘤病毒(HPV)宫颈癌筛查模式的有效性及联合宫颈细胞学p16~(INK4a)检测的价值。方法 2018年10—11月对贵州三都水族自治县和北京市门头沟地区3 905名30～59岁女性进行阴道自取样HPV宫颈癌筛查和宫颈细胞学p16~(INK4a)蛋白检测;对14种高危型HPV和p16~(INK4a)蛋白阳性者转诊阴道镜及定位活检,分析高危型HPV和p16~(INK4a)检出宫颈高级别病变(HSIL)及联合检测的效果。结果①3 905名女性阴道自取样本的合格率为100%,14种HPV阳性率16.08%(628/3 905),其中门头沟地区HPV阳性率16.45%(334/2 031),三都水族自治县HPV阳性率15.69%(294/1 874);单一HPV感染占72.77%(457/628);前5位HPV型别依次是HPV52、HPV16、HPV 58、HPV39和HPV68。②593例阴道镜下活检患者中,检出HSIL及以上病变62例(10.46%),其中HPV阳性61例(98.39%,61/62),包括HPV16/18阳性38例(62.30%,38/61),非HPV16/18阳性23例(37.71%,23/61),不同级别病变HPV阳性率比较,差异有统计学意义(P <0.01);③宫颈HSIL及以上病变、LSIL和宫颈炎中p16~(INK4a)蛋白表达的阳性率分别是90.33%、37.64%和19.27%(P <0.001),其检出宫颈HSIL及以上病变的敏感度、特异度、阴性预测值和准确度分别是90.33%、74.58%、98.51%和76.23%,其假阳性率(25.43%)明显低于HPV检测(80.04%)(P <0.001);HPV阳性联合p16~(INK4a)检测,在保持高敏感度(90.17%)的同时,特异度(83.46%)、准确度(84.30%)明显升高(P <0.05),假阳性率(16.55%)明显降低(P <0.05)。结论阴道自取样HPV检测宫颈癌筛查模式是可行的,可作为传统筛查模式的补充。宫颈细胞学p16~(INK4a)蛋白检测可用于对自取样HPV阳性/非HPV16/18的分流或精准筛查的方法。
Objective To investigate the effectiveness of human papillomavirus(HPV) cervical cancer screening model and the value of combined cervical cytology p16 detection. Methods 3 905 women aged 30～59 years were recruited for cervical cancer screening at Mentougou in Beijing and Sandu Aquatic Autonomous County in Guizhou province from October 2018 to November 2018. The specimensof cervical and vaginal cytology were taken form vaginal self-sampling. Highrisk HPV type in self-sampling and p16 protein in cervical cytology were detected. The patients with 14 types high-risk HPV and p16 protein positive were referred to colposcopy and the lesion site was biopsied. The screening effect of high-risk HPV and p16 protein to detect high-grade cervical lesions(HSIL) and combined detection was analyzed. Results ① The qualified rate of vaginal samples in 3 905 female was 100%, and the positive rate of 14 HPV types was 16.08%(628/3 905), among which the HPV positive rate in Mentougou region was 16.45%(334/2 031), and the HPV positive rate in Sandu region was 15.69%(294/1 874). Single HPV infection was 72.77%(457/628). The proportion of the top 5 HPV positive was HPV52, HPV16, HPV58, HPV39 and HPV68, respectively. ② Among the 593 patients who underwent biopsy under colposcopy, 62 cases(10.46%) of HSIL lesions were detected, among which 61 cases(98.39%, 61/62) were HPV positive, 62.30%(38/61) were HPV16/18, and37.71%(23/61) were non-HPV16/18, and the difference was statistically significant(P < 0.001). ③ The detection rates of p16 for HSIL +, LSIL and cervici tis were 90.33%, 37.64% and 19.27%, respectively, and the difference was statistically significant(P < 0.001).The sensitivity, specificity, negative predictive value and accuracy of HSIL+ were 90.33%, 74.58%, 98.51% and76.23%, respectively, and the false positive rate(25.43%) was significantly lower than that of HPV(80.04%). When HPV testing combimed with p16 testing, high sensitivity(90.17%) were maintained, while the specificity(83.46%), accuracy(84.30%)and false positive rate(16.55%) were significantly reduced(P < 0.05). Conclusion The model of cervical cancer screening by HPV detection of self-sampling is feasible and can be used as a supplement to the traditional cervical screening model. The cervical cytology p16 protein test can be used for self-sampling HPV positive/non-HPV16/18 triage or precision screening.
Objective To investigate the effectiveness of human papillomavirus(HPV) cervical cancer screening model and the value of combined cervical cytology p16 detection. Methods 3 905 women aged 30～59 years were recruited for cervical cancer screening at Mentougou in Beijing and Sandu Aquatic Autonomous County in Guizhou province from October 2018 to November 2018. The specimensof cervical and vaginal cytology were taken form vaginal self-sampling. Highrisk HPV type in self-sampling and p16 protein in cervical cytology were detected. The patients with 14 types high-risk HPV and p16 protein positive were referred to colposcopy and the lesion site was biopsied. The screening effect of high-risk HPV and p16 protein to detect high-grade cervical lesions(HSIL) and combined detection was analyzed. Results ① The qualified rate of vaginal samples in 3 905 female was 100%, and the positive rate of 14 HPV types was 16.08%(628/3 905), among which the HPV positive rate in Mentougou region was 16.45%(334/2 031), and the HPV positive rate in Sandu region was 15.69%(294/1 874). Single HPV infection was 72.77%(457/628). The proportion of the top 5 HPV positive was HPV52, HPV16, HPV58, HPV39 and HPV68, respectively. ② Among the 593 patients who underwent biopsy under colposcopy, 62 cases(10.46%) of HSIL lesions were detected, among which 61 cases(98.39%, 61/62) were HPV positive, 62.30%(38/61) were HPV16/18, and37.71%(23/61) were non-HPV16/18, and the difference was statistically significant(P < 0.001). ③ The detection rates of p16 for HSIL +, LSIL and cervici tis were 90.33%, 37.64% and 19.27%, respectively, and the difference was statistically significant(P < 0.001).The sensitivity, specificity, negative predictive value and accuracy of HSIL+ were 90.33%, 74.58%, 98.51% and76.23%, respectively, and the false positive rate(25.43%) was significantly lower than that of HPV(80.04%). When HPV testing combimed with p16 testing, high sensitivity(90.17%) were maintained, while the specificity(83.46%), accuracy(84.30%)and false positive rate(16.55%) were significantly reduced(P < 0.05). Conclusion The model of cervical cancer screening by HPV detection of self-sampling is feasible and can be used as a supplement to the traditional cervical screening model. The cervical cytology p16 protein test can be used for self-sampling HPV positive/non-HPV16/18 triage or precision screening.
引文
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[6]Mao C,Kulasingam SL,Whitham HK,et al.Clinician and patient acceptability of self-collected human papillomavirus testing for cervical cancer screening[J].J Womens Health(Larchmt),2017,26(6):609-615.
[7]Wu RF,Du H,Belinson SE,et al.Secondary screen in after primary self-sampling for HPV from SHENCCASTⅡ[J].J Low Genit Tract Dis,2012,16(4):416-420.
[8]Du H,Yi J,Wu RF,et al.A new PCR-based mass spectrometry system for high-risk HPV,PartⅡclinical trial[J].Am J Clin Pathol,2011,136(6):920-923.
[9]魏丽惠,赵昀,沈丹华,等.中国子宫颈癌筛查及异常管理相关问题专家共识(一)[J].中国妇产科临床杂志,2017,18(2):190-192.
[10]Zhang G,Yang B,Abdul-Karim FW.p16 immunohistochemistry is useful in confirming high-grade squamous intraepithelial lesions(HSIL)in women with negative HPV testing[J].Int J Gynecol Pathol,2015,34(2):180-186.
[11]Kishore V,Patil AG.Expression of p16INK4a Protein in cervical intraepithelial neoplasia and invasive carcinoma of uterine cervix[J].J Clini Diagn Res,2017,11(9):EC17-EC20.
[2]吴瑞芳,魏丽惠.基于HPV检测的自取样方法是子宫颈癌筛查的可行之路[J].中国妇产科临床杂志,2018,19(1):1-3.
[3]Bergeron C,Ikenberg H,Sideri M,et al.Prospective evaluation of p16/Ki-67 dual-stained cytology for managing women with abnormal Papanicolaou cytology:PALMS study results[J].Cancer Cytopathol,2015,123(6):373-381.
[4]Arbyn M,Verdoodt F,Snijders PJ,et al.Accuracy of human papillomavirus testing on self-collected versus clinician-collected samples:a meta-analysis[J].The Lancet Oncol,2014,15(2):172-183.
[5]李静然,孟元元,王悦,等.阴道自取样人乳头瘤病毒检测用于子宫颈癌筛查的有效性研究[J].中国妇产科临床杂志,2018,19(4):311-314.
[6]Mao C,Kulasingam SL,Whitham HK,et al.Clinician and patient acceptability of self-collected human papillomavirus testing for cervical cancer screening[J].J Womens Health(Larchmt),2017,26(6):609-615.
[7]Wu RF,Du H,Belinson SE,et al.Secondary screen in after primary self-sampling for HPV from SHENCCASTⅡ[J].J Low Genit Tract Dis,2012,16(4):416-420.
[8]Du H,Yi J,Wu RF,et al.A new PCR-based mass spectrometry system for high-risk HPV,PartⅡclinical trial[J].Am J Clin Pathol,2011,136(6):920-923.
[9]魏丽惠,赵昀,沈丹华,等.中国子宫颈癌筛查及异常管理相关问题专家共识(一)[J].中国妇产科临床杂志,2017,18(2):190-192.
[10]Zhang G,Yang B,Abdul-Karim FW.p16 immunohistochemistry is useful in confirming high-grade squamous intraepithelial lesions(HSIL)in women with negative HPV testing[J].Int J Gynecol Pathol,2015,34(2):180-186.
[11]Kishore V,Patil AG.Expression of p16INK4a Protein in cervical intraepithelial neoplasia and invasive carcinoma of uterine cervix[J].J Clini Diagn Res,2017,11(9):EC17-EC20.