| Objectives1. To Analysis the application of HPV E6 / E7 m RNA detection and HPV DNA genotyping testing in screening of cervical lesions with the gold standard of histopathological results.2. To explore the diagnostic value of DNA ploity quantitative analysis and TCT with sensitivity and specificity in screening of cervical lesions.3. To evaluate the economic efficiency by cost-effect analysis of TCT combined DNA ploity quantitative analysis using in different screening strategies.Methods1. A total of 240 cases were Selected for cervical diseases screening in the first affiliated hospital of Jinan university in September 2014 to October 2015. 240 cases were screened by HPV DNA genotyping testing and HPV E6 / E7 m RNA detection and 159 cases were confirmed by histopathological examination. HPV DNA genotyping testing used PCR amplification and Flow-through hybridization and gene chip technology. HPV E6 / E7 m RNA detection used hybrid capture and signal amplification technology.2. 364 patients, which as research object, were taken thinprep cytologic test(TCT), DNA ploity quantitative analysis and histopathological examination for cervical diseases screening from September 2014 to September 2014 in the first affiliated hospital of Jinan university. The age range was 22 to 72 years. Cervical cells were brushed to make two pieces liquid-base thinpreparation cytologic test and conventional cytology diagnosis using pap staining. DNA quantitative measurement was using Fe ulgen DNA staining.3. Selected 9514 patients screening by TCT and cell DNA ploity quantitative analysis from June 10, 2011 to October 16, 2015 as the research object. TCT, TCT parallel combined DNA ploity quantitative analysis and TCT serial combined DNA ploity quantitative analysis were three screening strategies for cervical diseases screening. Estimating cost and price of the TCT and DNA ploity quantitative analysis according to the 2015 guangdong medical services price charge pricing standards.ResultsChapter 11. There were 122 patients with positive result of HPV E6 / E7 m RNA in 240 patients. The number of positive HPV DNA examination was 195. There were 4 invalid samples of TCT testing, 140 samples of NILM, 24 samples of ASCUS, 8 samples of ASC-H, 22 samples ofLSIL; 32 samples of HSIL, 10 samples of Cervical cancer. 159 cases of patients were examined by histopathological test. There were 45 cases of Normal or chronic cervicitis, 16 cases of CIN I, 20 cases of CIN II, 42 cases of CINⅢ, 36 cases of invasive cervical cancer.2. In the five groups of pathological grading, HPV E6 / E7 m RNA detection and HPV DNA types of Kappa value respectively was 0.1, 0.05, 0.17, 0.31, 0.00, and overall Kappa value was 0.17(P = 0.014).3. The sensitivity of HPV DNA genotyping testing was 89.5 %, which significantly higher than that of HPV E6 / E7 m RNA detection(83.3 %)(χ~2=1.829,P=0.176). The specificity of HPV E6 / E7 m RNA detection and HPV DNA genotyping testing were 55.6 % and 11.1 %. The specificity of HPV E6 / E7 m RNA detection were significantly higher than those of DNA detection(χ~2 = 20.000, P < 0.001); Negative predictive value(NPV) of HPV E6 / E7 m RNA detection and DNA genotyping testing were 56.8 % and 29.4 %, but there was not statistically significant difference(χ~2= 3.685, P = 0.055). HPV E6 / E7 m RNA positive predictive value was 82.6 %, which higher than 71.8 % of HPV DNA genotyping testing and had statistical difference(χ~2 =4.124, P = P=0.042). The coincidence rate for HPV E6 / E7 m RNA detection and histopathological diagnosis was 75.5 %, HPV DNA genotyping testing coincidence rate was 67.3 %. Coincidence rate between HPV E6 / E7 m RNA detection and HPV DNA genotyping testing had no statistical difference(χ~2 = 2.602, P = 0.107).4. HPV E6 / E7 m RNA detection AUC of the ROC curve was0.717 and standard error(SE) was 0.046, and had no statistical difference compare with the null hypothesis area. The 95 % confidence interval of the AUC was(0.627, 0.807), the threshold of diagnosis of HPV E6 / E7 m RNA detection is 1.045, the sensitivity and specificity are 0.825 and 0.600.Chapter 21. 364 cases of study were tested by cell DNA ploity quantitative analysis and TCT, and using pathological examination as the gold standard. DNA ploity quantitative analysis: 161 cases were negative, 105 cases were suspected and 98 cases were positive. 364 cases regularly check TCT: 165 cases of negative, 97 cases of ASCUS, 102 cases of ASC-H+, 22 cases of ASC-H, 45 cases of LSIL, 25 cases of HSIL, 5 cases of AGC, 4 cases of cervical cancer and 1 case of endometrial carcinoma in. Histopathological examination: normal 8 cases, 197 cases of chronic cervicitis, CINⅠ 36 cases, CINⅡ 31 cases, CINⅢ 15 cases, carcinoma in situ 37 cases of invasive cervical cancer 38 cases and endometrial carcinoma 2 cases.2. Kappa value of the two testing methods in five groups were respectively 0.052(P = 0.439), 0.161(P = 0.370), 0.037(P = 0.833), 0.420(P =0.002) and 0.475(P = 0.013). Endometrial cancer cases had no statistical analysis because of less numbers. Overall Kappa value of two methods was 0.435(P < 0.01).3. The sensitivity of cell DNA ploity quantitative analysis was 49.1 %, which lower than the TCT(50.9 %) and had no statistically significant difference(χ~2= 0.038, P = 0.038). There was no statistically significant difference(χ~2 = 0.001, P = 0.970) between the speciality of DNA ploity quantitative analysis(90.2 %) and TCT(9.8 %). The Cell DNA ploity quantitative analysis negative predictive value was 69.5 % and TCT was 70.2 %, there was no statistically significant difference(χ~2 = 0.005, P = 0.943); Cell DNA ploity quantitative analysis positive predictive value was 79.6 %, which had no statistically significant compare with TCT detection(79.4 %)(χ~2 = 0.000, P =0.991). Coincidence rate between cell DNA ploity quantitative analysis and the gold standard diagnosis was 72.3 %, and that of TCT was 72.8 %, there was no statistically significant difference(χ~2 = 0.004, P =0.947).4. The sensitivity and specificity of cell DNA ploity quantitative analysis parallel combined TCT were 75.0 % and 80.9 %.Using TCT for first, the sensitivity of TCT serial combined cell DNA ploity quantitative analysis for cervical disease screening were 24.9 %, but the specificity was up to 99.0 %.5. There were 63 inflammation/normal cases in 97 cases of ASCUS, which pathological negative rate was 67.0 %. Cell DNA ploity quantitative analysis results were negative and the pathological diagnosis of inflammatory/normal, CIN Ⅰ, CIN Ⅱ, CIN Ⅲ and infiltrating carcinoma respectively were 86.0 %, 7.0 %, 0 %, 7.0 %, 0 %. The general pathological positive rate is 14.0 %; cell DNA ploity quantitative analysis results was suspicious positive, and pathologic diagnosis of inflammatory/normal, CIN Ⅰ, CIN Ⅱ, CIN Ⅲ and infiltrating carcinoma were 54.8 %, 9.7 %, 16.1 %, 16.1 %, 3.2 %, the general pathological positive rate is 45.2 %; Cell DNA ploity quantitative analysis result was positive, the pathological diagnosis of inflammatory/normal, CIN Ⅰ, CIN Ⅱ, CIN Ⅲ and infiltrating carcinoma were 47.8 %, 17.4 %, 13.0 %, 17.4 %, 4.3 %, and the general pathological positive rate was 52.2 %.6. The cell DNA ploity quantitative analysis’ AUC was 0.763 and SE was 0.026, P = 0.000, 95 % confidence interval was(0.711, 0.711), cell DNA ploity quantitative analysis diagnosis threshold was 1.5, sensitivity was 0.792 and specificity was 0.624. TCT’s AUC was 0.716, and the SE was 0.716(P = 0.000), 95 % confidence was 0.661 to 0.772. The diagnosis threshold of TCT was 2.5, the sensitivity was 0.509 and specificity was 0.898. Comparing the AUC between Cell DNA times ploity quantitative analysis and TCT, there was no statistically significant difference(Z = 1.230, P = 1.230).Chapter 31. The study included 9514 cases which taken cell DNA ploity quantitative analysis and TCT for cervical screening. Cell DNA ploity quantitative analysis included 8445 cases of negative, 527 cases of suspicious results and a total of 98 cases of positive. 444 cases were "invalid or interference results”. TCT examination included 8851 cases of negative, 184 cases of ASCUS, 22 cases of ASC-H, 5 cases of "AGC", 44 cases of "LSIL," "HSIL" 24 cases, 7 cases of carcinoma, 377 cases of invalid specimens and a total of 609 cases of invalid or interference results. According to the screening results, patients who underwent colposcopy and biopsy included 102 cases of TCT positive, 97 cases of ASCUS, 98 positive cases and 105 suspected positive cases of DNA ploity quantitative analysis.2. There were 444 cases and 609 cases of “invalid or interference results” in cell DNA ploity quantitative analysis and TCT screening. Interference rate of cell DNA ploity quantitative analysis and TCT were 4.67 % and 6.40 % respectively. The results of the two groups had no statistically significant difference(χ~2 = 27.37, P < 0.01).3. The three kinds of screening strategies in 9514 cases made comparison by cost-effective analysis. TCT screening strategy: the total cost of 2, 069, 684 yuan and 81 cases were diagnosed positive of cervical lesions base on pathological results. Each positive patient cost 25551.7 yuan. TCT parallel combined DNA ploity quantitative analysis strategy: a total cost of 3, 513, 137 yuan and 171 cases of pathological results were diagnosed positive cervical lesion. Each patient cost was 30 026.8 yuan. TCT serial combined DNA ploity quantitative analysis screening strategy: total cost of 2, 110, 814 yuan and 100 cases of positive pathological results. Each patient cost was 21108.1 yuan. DNA ploity quantitative analysis serial combined TCT screening strategy: total cost of 1,651,309 yuan and 113 cases of positive pathological results. Each patient cost was 14 613.4 yuan.4. TCT parallel combined DNA ploity quantitative analysis strategy had 40 095.9 yuan/cases of incremental cost effectiveness ratio than TCT strategy. TCT serial combined DNA ploity quantitative analysis screening strategy had 2164.5 yuan/example of incremental cost effectiveness ratio than TCT strategy. DNA ploity quantitative analysis serial combined TCT screening strategy had-13 074.2 yuan/example of incremental cost effectiveness ratio than TCT strategy.ConclusionsChapter 11. HPV E6 / E7 m RNA detection of cervical lesions has a higher specificity and positive predictive value than the HPV DNA genotyping testing.2. The diagnosis coincidence rate of HPV E6 / E7 m RNA detection was higher than that of HPV DNA genotyping testing.3. HPV E6 / E7 m RNA detection can be used for preliminary screening for cervical cancer.Chapter 21. The cell DNA ploity quantitative analysis screening has good shunt effect in ASCUS.2. TCT parallel combined DNA ploity quantitative analysis strategy can improves the sensitivity for the diagnosis of cervical lesions. TCT serial combined DNA ploity quantitative analysis screening strategy can improve the specificity for the diagnosis of cervical lesions.3. The cell DNA ploity quantitative analysis of cervical lesions has good diagnostic value.Chapter 31. he interference rate of TCT was higher than cell DNA ploity quantitative analysis.2. DNA ploity quantitative analysis can be used for preliminary screening for cervical cancer, DNA ploity quantitative analysis serial combined TCT screening strategy has obvious advantages of health economics. |
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