外用红色诺卡氏菌细胞壁骨架治疗高危型HPV持续感染伴或不伴低级别鳞状上皮内病变临床疗效的前瞻性研究

The clinical efficacy of topical Nocardia rubra cell wall skeleton in the treatment of high-risk HPV persistent infection with or without LSIL:a prospectively study

目的探讨外用红色诺卡氏菌细胞壁骨架(Nocardia rubra cell wall skeleton,Nr-CWS)治疗高危型人乳头瘤病毒(high-risk human papillomavirus,HR-HPV)持续感染伴或不伴低级别鳞状上皮内病变(low-grade squamous intraepithelial lesion,LSIL)的临床疗效。方法采用前瞻性研究收集2018年1月至2020年3月郑州大学第一附属医院高危型人乳头瘤病毒(HR-HPV)持续感染伴或不伴LSIL的患者108例,按照3∶1的比例随机分为研究组(81例)和对照组(27例),完成随访94例,其中研究组68例,对照组26例。研究组给予宫颈局部应用Nr-CWS,对照组给予不含Nr-CWS的安慰剂。比较两组治疗后的1、4、8、12个月HPV转阴及不良反应发生情况。结果治疗后1个月,研究组和对照组有效率分别为19.12%(13/68)和3.85%(1/26),两组比较,差异无统计学意义(P>0.05);治疗后4、8、12个月研究组的有效率分别为54.41%(37/68)、72.06%(49/68)和82.35%(56/68),对照组的有效率分别为23.08%(6/26)、38.46%(10/26)和38.46%(10/26),两组比较,差异均有统计学意义(P均<0.05)。在研究组中,治疗后12个月,HPV16、HPV18和非HPV16/18的有效率分别为82.61%(19/23)、62.50%(5/8)和84.21%(32/38),三组间比较,差异无统计学意义(P>0.05);伴LSIL的HR-HPV持续感染和不伴LSIL的HR-HPV持续感染组有效率[85.19%(23/27)和80.49%(33/41)]比较,差异无统计学意义(P>0.05)。研究组和对照组治疗中分泌物增多等不良反应的发生率分别为8.82%(6/68)和7.69%(2/26),差异无统计学意义(P>0.05)。结论外用Nr-CWS治疗HR-HPV持续感染或伴LSIL的HRHPV持续感染者有一定的疗效。

Objective To prospectively estimate the clinical efficacy of topical Nocardia rubra cell wall skeleton(Nr-CWS)in the treatment of high-risk HPV persistent infection with or without LSIL.Methods From January 2018 to March 2020,108 subjects with HR-HPV persistently infected for 12 months or more with or without LSIL who visited in The First Affiliated Hospital of Zhengzhou University were selected and randomly divided into 2 groups according to the ratio of 3∶1.The test group(81 cases)was given Nr-CWS by topical,and the control group(27 cases)was treated with placebo.A total of 94 cases were followed up,including 68 cases in test group and 26 cases in control group.The efficacy of the two groups was compared at 1,4,8 and 12 months after treatment,through HPV negative conversion,and the occurrence of adverse reactions between the two groups were compared.Results One month after treatment,the effective rate of the test group and the control group was 19.12%(13/68)and 3.85%(1/26),respectively,and there was no statistical significance between the two groups(P>0.05).At 4,8 and 12 months after treatment,the effective rates of the test group were 54.41%(37/68),72.06%(49/68),82.35%(56/68),and the control group were 23.08%(6/26),38.46%(10/26),38.46%(10/26),respectively.The difference between the two groups was statistically significant(P<0.05).In the study group,12 months after treatment,the effective rates of HPV16,HPV18 and non-HPV16/18 were 82.61%(19/23),62.50%(5/8)and 84.21%(32/38),respectively,and there was no statistical significance among the three groups(P>0.05).The effective rates of HR-HPV persistent infection with LSIL and HR-HPV persistent infection without LSIL were 85.19%(23/27)and 80.49%(33/41),respectively,with no statistical significance(P>0.05).The incidence of adverse reactions including increased secretions was 8.82%(6/68)and 7.69%(2/26)in the test group and the control group,respectively,with no statistical significance(P>0.05).Conclusions Nr-CWS is effective in the treatment of persistent HR-HPV infection,and it is also effective in the treatment of persistent HR-HPV infection with LSIL.