目的 探讨p16/Ki-67染色、HPV E6/E7mRNA和联合检测对HSIL+病变诊断的临床价值。方法 募集2017年3月—2020年8月期间,于中山市博爱医院妇产科就诊,组织学证实为宫颈炎患者209例、LSIL患者169例、HSIL患者131例和宫颈癌患者86例作为研究对象,回顾分析研究对象术前细胞学样本p16/Ki-67染色、HPV E6/E7mRNA检测结果,纵向比较p16/Ki-67染色、HPV E6/E7mRNA和联合检测在不同级别宫颈病变的阳性率的差异,横向比较p16/Ki-67染色、HPV E6/E7mRNA和联合检测在相同宫颈病变的阳性率的差异,综合评估p16/Ki-67染色、HPV E6/E7mRNA和联合检测诊断HSIL+病变效能的差异。结果 ①纵向比较:p16/Ki-67染色、HPV E6/E7mRNA和联合检测阳性率随宫颈病变程度的加重呈趋势性升高(p16/Ki-67染色:χ²=374.34,P<0.001;HPV E6/E7mRNA检测:χ²=289.21,P<0.001;联合检测:χ²=343.90,P<0.001)。②横向比较:在宫颈炎、LSIL、宫颈癌组,p16/Ki-67染色、HPV E6/E7mRNA和联合检测阳性率之间差异均不具有统计学意义(均P>0.05)。在HSIL组,p16/Ki-67染色和联合检测之间阳性率差异有统计学意义(χ²=8.09,P=0.004); HPV E6/E7mRNA和联合检测之间阳性率差异有统计学意义(χ²=11.30,P=0.001)。③p16/Ki-67染色、HPV E6/E7mRNA和联合检测诊断HSIL+的灵敏度,总体差异有统计学意义(χ²=7.69,P=0.021)。p16/Ki-67染色与联合检测法之间的灵敏度差异有统计学意义(χ²=7.29,P=0.007);HPV E6/E7mRNA检测与联合检测法之间的灵敏度差异有统计学意义(χ²=4.84,P=0.028)。p16/Ki-67染色、HPV E6/E7mRNA和联合检测诊断HSIL+的特异度及符合率的总体差异不具有统计学意义(χ²₁=5.38,P₁=0.068;χ²₂=0.93,P₂=0.628)。结论 p16/Ki-67染色、HPV E6/E7mRNA 和联合检测均可有效筛出HSIL+病变,但是联合检测能显著提高HSIL+病变诊断的灵敏度,降低漏诊率,同时保持了较好的特异度和符合率,建议将p16/Ki-67染色和HPV E6/E7mRNA联合检测作为早期诊断HSIL+病变的策略。

Objective To investigate the clinical value of p16/Ki-67 staining E6/E7 mRNA and combined detection in the diagnosis of HSIL+ lesions. Methods From March 2017 to August 2020,209 cases of cervicitis,169 cases of LSIL,131 cases of HSIL and 86 cases of cervical cancer confirmed by histology were selected as the research objects. The results of p16/Ki-67 staining and HPV E6/E7 RNA detection of the preoperative cytological samples were retrospectively analyzed and the p16/Ki-67 staining and HPV E6/E7 mRNA detection results were compared longitudinally. The positive rates of E6/E7mRNA and combined detection in different grades of cervical lesions were compared.The positive rates of p16/Ki-67 staining,HPV E6/E7 mRNA and combined detection in the same cervical lesions were compared horizontally.The differences in the diagnostic efficacy of p16/Ki-67 staining,HPV E6/E7 mRNA and combined detection in the diagnosis of HSIL+lesions were comprehensively evaluated. Results ①Longitudinal comparison:the positive rates of p16/ Ki-67 staining, HPV E6/E7mRNA and combined detection increased with the severity of cervical lesions(p16/Ki-67 staining:χ²=374.34,P<0.001;HPV E6/E7 mRNA detection:χ²=289.21,P<0.001;joint detection:χ²=343.90,P<0.001). ②Transverse comparison: in cervicitis, LSIL and cervical cancer groups,there were no significant differences in the positive rates of p16/Ki-67 staining, HPV E6/E7 mRNA and combined detection (all P>0.05). In the HSIL group,there was significant difference in the positive rate between p16/Ki-67 staining and combined detection (χ²=8.09,P=0.004)and the difference between HPV E6/ E7 mRNA and combined detection was statistically significant(χ²=11.30,P=0.001). ③The sensitivity of p16/Ki-67staining,HPV E6/E7 mRNA and combined detection in the diagnosis of HSIL+ was statistically significant(χ²=7.69,P=0.021). The sensitivity difference between p16/Ki-67 staining and combined detection was statistically significant(χ²=7.29,P=0.007);the sensitivity difference between HPV E6/E7 mRNA detection and combined detection method was statistically significant (χ²=4.84,P=0.028). There was no significant difference in the specificity and coincidence rate of p16/Ki-67 staining,HPV E6/E7 mRNA and combined detection in the diagnosis of HSIL+(χ²₁=5.38,P₁=0.068;χ²₂=0.93,P₂=0.628). Conclusion P16/Ki-67 staining,HPV E6/E7 mRNA and combined detection may effectively screen out HSIL+ lesions,reduce the missed diagnosis rate, but the combined detection may significantly improve the sensitivity of diagnosis of HSIL+ lesions, while maintaining good specificity and coincidence rate.It is suggested that p16/Ki-67 staining and HPV E6/E7 mRNA detection should be used as a strategy for early diagnosis of HSIL+ lesions.

目的 调查I-IIa期宫颈鳞状细胞癌患者术后随诊和复发情况,并探索随诊和复发的相关因素。方法 分析2011年1月—2012年6月中山市妇幼保健院收治的128例宫颈鳞状细胞癌患者的临床资料,分析他们的术后随诊情况及其影响因素。将有液基薄层细胞学(TCT)及盆腔检查者视为有效随诊的患者,分析肿瘤复发情况及其影响因素。结果 128例患者中,有效随诊104例(占总人数的81.25%)。年龄组越小,随诊率越高(P=0.034);城市患者较农村患者,随诊率高(P=0.028);文化程度越高,随诊率越高(P=0.028);职业为公务员、教师、公司职员或自由职业、个体,随诊率比职业为家庭妇女和工人更高(P=0.030)。在104例随诊者中,2年复发8例(占7.7%)。临床分期较晚,肿瘤直径>4cm,病理类型,脉管内瘤栓阳性,淋巴结转移阳性是影响患者2年复发的危险因素(P<0.05)。结论 临床分期,肿瘤直径,脉管内瘤栓阳性,淋巴结转移等临床病理特征与患者复发密切相关。应针对宫颈癌患者社会人口学特点制定措施,提高随诊率。

Objective To investigate the follow-up rate after surgical treatment and the recurrence rate among patients with cervical squamous cell carcinoma in I-IIa stage, and identify associated factors. Methods The clinical data of 128 cases of cervical squamous cell carcinoma from January 2011 to June 2012 in Zhongshan maternal and child health hospital was collected. Follow up record of these cases was analyzed and factors associated with follow up were identified. Patients having taken thinprep liquid-based cytology test (TCT) and pelvioscopy were treated as cases being followed effectively, and their recurrence and associated factors were analyzed. Results Among the 128 patients, 104(81.25%) were effectively followed. Patients with younger age(P=0.034), living in city (P=0.028), with higher education level(P=0.028) had higher follow-up rate. Civil servants, teachers and freelancers had higher follow-up rate than housewives and workers (P=0.030).Eight of the 104 effectively followed cases recurred within two years after surgery, accounting for 7.7%. The associated factors of recurrence included clinical stage, tumor diameter, larger than 4cm, the depth of myometrial invasion, deeper than 2/3, vascular tumor thrombus positive, and lymph node metastasis positive (P<0.05). Conclusion Clinical stage, tumor size, vascular tumor thrombus positive, lymph node metastasis positive were associated with recurrence. Tailored strategies should be developed to improve the follow up rate based on the social and demographic characteristics of patients.