人乳头状瘤病毒分型检测在高级别宫颈上皮内瘤变患者LEEP治疗后随访中的价值

Value of human papillomavirus genotyping in follow- up of patients with high-grade cervical intraepithelial neoplasia after loop electrosurgical excision procedure

目的探讨人乳头状瘤病毒（HPV）分型检测在高级别宫颈上皮内瘤变（CIN）患者宫颈电热圈环切术（LEEP）治疗后随访中的价值。方法 373例CINⅡ~Ⅲ级患者行LEEP治疗后第6、12、24个月均进行HPV分型、HPV-DNA检测和新柏氏液基细胞学检测（TCT）,根据结果或有可疑病变者行宫颈病理活检,比较各年龄组患者术前HPV亚型感染及术后不同随访时间的HPV消除情况。结果 373例患者术前HPV感染率为95.44%;其中高危HPV感染率为91.42%,低危HPV感染率为1.88%;单一HPV亚型感染率为54.16%,双重或多重HPV亚型感染率为61.13%,多重感染最多可达4重感染。检出率排名前5位的亚型是HPV16、HPV58、HPV52、HPV18、HPV33,HPV16检出率明显高于其他各亚型,并在不同年龄组患者中均居第1位（P〈0.05）;低危型HPV以HPV11亚型最多见。在宫颈LEEP治疗后第6、12、24个月,HPV-DNA总转阴率分别为70.79%、81.46%和89.04%,HPV16/18亚型转阴率分别为75.65%、86.01%和93.26%,随着时间的延长,转阴率均明显升高（P〈0.05）;但≥50岁组患者中,术后6和12个月的HPV16/18亚型转阴率与术前比较差异无统计学意义,随着时间的延长,转阴率无明显变化（P〉0.05）。各年龄组术后6个月HPV-DNA转阴率比较差异无统计学意义（P〉0.05）,术后12和24个月HPV-DNA转阴率组间比较差异有统计学意义,≤40岁的年轻患者有更高的转阴率（P〈0.05）。各年龄组术后不同随访时间HPV16/18亚型转阴率比较差异有统计学意义,≤40岁年轻患者有更高的转阴率（P〈0.05）。结论 HPV在CINⅡ~Ⅲ患者中的感染率较高,尤其是HPV16亚型。术后第6个月HPV分型检测是LEEP治疗后监测疾病转归的一种较好方法。对年龄较大,术后HPV16亚型持续感染的患者应密切长时间随访。

Objective To explore the value of human papillomavirus（ HPV） genotyping in follow- up of patients with high-grade cervical intraepithelial neoplasia（ CIN） after loop electrosurgical excision procedure（ LEEP）. Methods HPV genotyping,HPV-DNA test,and Thin Prep cytology test（ TCT） were performed after 6,12,and 24 months of LEEP among 373 patients with CIN Ⅱ- Ⅲ,based on the detection results,the suspected cases underwent cervical pathological biopsy. HPV subtypes infection rates before LEEP and HPV clearance rates at different time points after LEEP during follow- up in different age groups were compared. Results Among 373 patients,HPV infection rate before LEEP was 95. 4%; the infection rates of high- risk HPV and low- risk HPV were 91. 42% and 1. 88%,respectively; the infection rates of single HPV subtype and double or multiple HPV subtype were 54. 16% and 61. 13%,respectively; the maximal number of HPV subtype in multiple infection was four. The top five HPV subtypes were HPV16,HPV58,HPV52,HPV18,and HPV33,respectively. The detection rate of HPV16 was significantly higher than those of other HPV subtypes,which ranked the first place among the patients in different age groups（ P〈0. 05）; among low- risk HPV subtypes,HPV11 was the most common subtype. After 6,12,and 24 months of LEEP,the total negative conversion rates of HPV- DNA were 70. 79%,81. 46%,and 89. 04%,respectively; the negative conversion rates of HPV16 /18 were 75. 65%,86. 01%,and 93. 26%,respectively,which increased significantly with time（ P〈0. 05）; among the patients aged 50 years old or more than 50 years old,there was no statistically significant difference in the negative conversion rates of HPV16 /18 between before LEEP and after 6 and 12 months of LEEP,which did not change significantly with time（ P〉0. 05）. There was no statistically significant difference in the negative conversion rate of HPV- DNA after 6 months of LEEP among different age groups（ P〉0. 05）,there was statistically significant difference in the negative conversion rate of HPV- DNA among different age groups after 12 and 24 months of LEEP,the negative conversion rate of HPV- DNA among the patients aged 40 years old or less than 40 years old was higher（ P〈0. 05）. There was statistically significant difference in the negative conversion rate of HPV16 /18 at different time points after LEEP during follow- up among different age groups,the negative conversion rate of HPV16 /18 among the patients aged 40 years old or less than 40 years old was higher（ P〈0. 05）. Conclusion The infection rate of HPV among the patients with CIN Ⅱ- Ⅲ was relatively high,especially HPV16 subtype. HPV genotyping at the sixth month after LEEP is a good method to monitor prognosis; for the older patients with persistent HPV16 infection after LEEP,long time and close follow- up is needed.