| Objective:To evaluate the effectiveness of HPV E6/E7 mRNA test in detecting and diagnosing high-grade cervical intraepithelial neoplasia and cervical cancer(HSIL+),with the aim of better managing HPV-positive women and providing a reference for improving cervical cancer screening protocols.Methods:Patients with abnormal cervical cancer screening results or the presence of cervical-related symptoms highly suspicious of cervical lesions who visited the gynecology clinic of the Second Hospital of Jilin University from October 2020 to October 2022 were collected and 257patients who underwent simultaneous HPV E6/E7 mRNA test,HPV testing,TCT and were referred for colposcopy for cervical biopsy were randomly selected for the study.The age distribution of HPV infection was analyzed.Using cervical histopathological diagnosis as the gold standard,the relationship between the positive rate of HPV E6/E7 mRNA test and the grade of cervical lesions was analyzed,with emphasis on assessing the screening and diagnostic efficacy of HPV E6/E7 mRNA test for HSIL+.Meanwhile,for HPV-positive patients,they were divided into two groups,HPV 16/18 positive and the remaining 12 HPV positive,and compared with TCT to assess how effective the HPV E6/E7 mRNA test was in screening and diagnosing HSIL+in these two groups.And further investigate the difference in efficacy of TCT,HPV E6/E7 mRNA alone or in combination to detect HSIL+in HPV-positive women.Results:1.The difference in the total HPV positive rates between the age groups was not statistically significant(χ~2=2.551,P=0.635).There was no statistically significant difference in HPV 16/18 positive rates among the three groups of patients aged 25 years and younger,26 to 55 years,and 56 years and older(χ~2=4.760,P=0.093).The remaining 12 HPV positive rates were significantly different among the three groups(χ~2=7.910,P=0.019),with significantly higher positive rate in patients aged 56 years and older than in patients aged 25 years and younger(χ~2=6.208,P=0.013)and between 26 and 55 years(χ~2=6.730,P=0.009);the differences in their positive rates between patients aged 25 years and younger and those aged 26 to 55 years were not statistically significant(χ~2=0.740,P=0.390).2.HPV E6/E7 mRNA positivity increased with increasing cervical lesion grade,and HPV E6/E7 mRNA positivity differed significantly between cervical lesion grades(χ~2=16.109,P<0.001)when cervical cancer cases were not included.HSIL positive rate was significantly higher than LSIL(χ~2=6.873,P=0.009)and chronic cervicitis(χ~2=16.039,P<0.001),but there was no significant difference in the positive rates between LSIL and chronic cervicitis(χ~2=2.432,P=0.119).After inclusion of cervical cancer cases,the HPV E6/E7 mRNA positive rate was significantly higher in the HSIL+group than in the LSIL-group(χ~2=15.359,P<0.001);the HPV positive rate was significantly higher in the HSIL+group than in the LSIL-group(χ~2=4.783,P=0.029);no significant difference was seen between the TCT positive rates in the HSIL+group and the LSIL-group(χ~2=1.220,P=0.269).3.The area under the curve(AUC)of the ROC for HPV E6/E7mRNA test in screening HSIL+patients was 0.647(P=0.001),with a95%confidence interval of 0.570～0.724.The sensitivity,specificity,positive predictive value,negative predictive value,and diagnostic compliance of HPV E6/E7 mRNA test were 81.82%,47.52%,29.80%,90.57%,and 54.86%,respectively.The corresponding results of HPV test were 92.73%,19.80%,23.94%,90.91%,35.41%,respectively.The corresponding results of TCT were 61.82%,46.53%,23.94%,81.74%,49.81%,respectively.The sensitivity of HPV E6/E7 mRNA was similar to that of HPV test in detection of HSIL+(χ~2=2.946,P=0.086),while the specificity was significantly higher than that of HPV test(χ~2=34.760,P<0.001).The specificity of HPV E6/E7 mRNA was similar to that of TCT in detection of HSIL+(χ~2=0.040,P=0.842),while the sensitivity was significantly higher than that of TCT(χ~2=5.435,P=0.020).4.The sensitivity(χ~2=1.957,P=0.162)and specificity(χ~2=0.530,P=0.585)of HPV E6/E7 mRNA were similar to those of TCT in detection of HSIL+in the HPV 16/18 positive women.The specificity(χ~2=0.551,P=0.458)of HPV E6/E7 mRNA was similar to that of TCT in detection of HSIL+in the other 12 types of HPV positive women,while the sensitivity(χ~2=5.939,P=0.015)was significantly higher than that of TCT.5.For HPV-positive women,three testing protocols were adopted.There was a statistically significant difference in sensitivity between the three testing protocols(χ~2=14.092,P=0.001),where the sensitivity of the HPV E6/E7 mRNA test was significantly higher than that of the combined HPV E6/E7 mRNA,TCT(χ~2=13.909,P<0.001)and TCT(χ~2=6.800,P=0.009);there was no statistical difference in sensitivity between the combined HPV E6/E7 mRNA,TCT and TCT(χ~2=1.417,P=0.234).There was a statistically significant difference in specificity between the three protocols(χ~2=31.774,P<0.001),where the specificity of HPV E6/E7 mRNA and TCT combined test was significantly higher than that of TCT(χ~2=19.543,P<0.001)and HPV E6/E7 mRNA test(χ~2=28.949,P<0.001);no significant difference was found in the specificity between TCT and HPV E6/E7 mRNA test(χ~2=1.000,P=0.317).Conclusion:1.There was a significant association between HPV E6/E7 mRNA test positivity and cervical lesion grade.2.The specificity of HPV E6/E7 mRNA test was significantly higher than that of HPV assay,the sensitivity was significantly higher than that of TCT,and the screening and diagnostic efficacy for HSIL+was higher.3.For HPV-positive women,HPV E6/E7 mRNA test is highly sensitive and does not lose specificity,and the screening and diagnostic efficacy is superior to that of TCT.4.HPV E6/E7 mRNA test can be an option for primary cervical cancer screening modalities,and its alone or in combination can provide good stratification of the HPV-positive population. |
PDF Full Text Request