| Objective:To evaluate the screening performance of two cervical cancer primary screening methods,Visual Inspection with Acetic Acid/Lugol’s Iodine(VIA/VILI)and Human Papillomavirus(HPV),in low health resource areas of Xinjiang under the conditions of primary health service level;to evaluate the efficacy of the Colposcopic Artificial Intelligence Auxiliary Diagnostic System(CAIADS)in assisting clinical diagnosis and guiding biopsy by junior colposcopists;and to evaluate the performance of the HPV E7 immunohistochemical staining technique in classifying cervical lesions.This study aims to give a scientific basis for deciding suitable cervical cancer screening strategy for lowresource areas in China,improve the quality of population screening,provide powerful data support for clinical precision diagnosis and treatment,and propose more optimal screening and diagnostic strategies to reach the "90-70-90" goal of global cervical cancer elimination call.Methods:Part Ⅰ:A prospective cohort study was conducted recruiting a total of 2986 eligible women(aged 35-65 years)in 2015 in Bachu County,Kashgar,Xinjiang for cervical cancer screening,and a total of 2284 women were followed up in 2017(follow-up rate 76.5%).Women with HPV or VIA positive results were referred to colposcopy examination,and abnormal colposcopy were biopsied for final pathological diagnosis.Performance of primary screening methods(HPV and VIA/VILI)was evaluated using the CIN2+(cervical intraepithelial neoplasia grade 2 or worse)cases detected during 3 years of follow-up period.And risk factors associated with the persistent HPV infection and the occurrence of CIN2+.Part Ⅱ:A total of 366 out of 1146 women with complete medical information recorded by senior colposcopist,and valid histology results were included between September 2021 and January 2022.Anonymized colposcopy images were reviewed by CAIADS and a junior colposcopist separately,and the junior colposcopist reviewed the colposcopy images with CAIADS results(named CAIADS-Junior).The diagnostic accuracy and biopsy efficiency of CAIADS and CAIADS-Junior were assessed in detecting CIN2+,CIN3+,and cancer in comparison with the senior and a junior colposcipist.The factors influencing the accuracy of CAIADS were explored.Part III:A total of 72 inpatients or outpatient women with cervical lesions who were treated in Xinjiang Cancer Hospital between 2019 and 2021 were included.The expression levels of P16,Ki-67 and HPV E7 proteins were evaluated using a parallel double-blind immunohistochemical staining methods,and the diagnostic accuracy was evaluated and compared with each other.Results:Part Ⅰ:1)Screening abnormality rates of HPV screening arm and VIA arm:in 2015 and 2017,the positivity of HPV was higher than VIA/VILI(2015,10.7%vs 8.5,P=0.059;2017,8.7%vs.3.0%,P<0.001),besides the detection rate of CIN2+in HPV screening arm was also higher than that of VIA arm(2015,0.9%vs 0.4%,P=0.132;2017,0.8%vs 0.2%,P=0.004).2)Primary screening performance of HPV and VIA/VILI for cervical cancer:in 2015,VIA/VILI group and HPV group had similar sensitivity(100.0%vs 100.0%,P=1.000)and specificity(90.1%vs 91.9%,P=0.079),with no significantly statistical differences.In 2017,the sensitivity of HPV screening performance was significantly higher than that of VIA/VILI test,90.0%(18/20)and 25.0%(5/20)(P<0.001).However,the specificity,positive predictive value,and negative predictive value were similar,with no significantly statistical differences(P>0.05).Meanwhile,using all CIN2+detected in 3 years as outcome,,the screening sensitivity of HPV was still significantly better than VIA/VILI,94.6%(35/37)and 37.5%(9/24),respectively(P<0.001);Part II:1)Evaluation of the diagnostic effect of CAIADS assisted by junior colposcopist:for CIN2+and CIN3+detection,CAIADS showed the sensitivity at～80%which was not significantly lower than senior colposcopist(for CIN2+:80.6%vs 91.3%,P=0.061 and for CIN3+:80.0%vs 90.0%,P=0.189).The sensitivity of junior colposcopist was increased significantly with assistance of CAIADS(for CIN2+:95.1%vs 79.6%,P=0.002 and for CIN3+:97.1%vs 85.7%,P=0.039),and were comparable to those of senior colposcopist(for CIN2+:95.1%vs 91.3%,P=0.388 and for CIN3+:97.1%vs 90.0%,P=0.125).In detecting cervical cancer,CAIADS achieved the highest sensitivity at 100%;2)Evaluation of the diagnostic effect of CAIADS assisted junior colposcopist in guiding biopsies:For all endpoints,CAIADS showed the highest specificity(55-64%)and positive predictive values compared to senior and junior colposcopist.When CIN grades became higher,the average biopsy numbers decreased for the subspecialists and CAIADS required minimum number of biopsies to detect per case(2.2-2.6 cut-points).Meanwhile,the biopsy sensitivity of junior colposcopist was the lowest,but CAIADS assisted junior colposcopist to achieve a higher biopsy sensitivity;Part Ⅲ:1)Expression levels of P16,Ki-67,and HPV E7 in different cervical lesions:The positive rate of P16,Ki-67,and HPV E7 proteins were linearly distributed along with the different pathological grades,and the expression positive rate tended to increase with the severity of pathological grades,with significantly statistical differences(Ptrend<0.001);2)Evaluation of diagnostic efficacy of P16,Ki-67 and HPV E7 proteins:if the expression level of 1+was used as the threshold,regarding CIN2+,CIN3+and cancer detection,the sensitivity of HPV E7 protein was the highest(above 97%),which were higher than P16 and Ki-67(for HPV E7 vs P16:CIN2+,97.4%vs 84.2%,P=0.063;CIN3+,100.0%vs 93.8%,P=0.405;for HPV E7 vs Ki-67:CIN2+,97.4%vs 84.2%,P=0.063;CIN3+,100.0%vs 100.0%,P=1.000).3)Evaluation of the diagnostic efficacy of the combined application of P16,Ki-67 and HPV E7 protein:in detecting CIN2+,the specificity of P16 and E7(2+),Ki-67 and E7(2+),P16(1+)and E7(2+),Ki-67(1+)and E7(2+)reached 100%;the sensitivity of P16 or E7(1+),Ki-67 or E7(1+),Ki-67(2+)or E7(1+)was 97.4%;when the sensitivity and specificity of P16 or E7(2+)were 81.6%and 94.1%,the number of under-or overdiagnosed cases was the lowest(9 cases).Conclusions:Part Ⅰ:1)careHPV testing was accurate and objective,which it is of great value to be used as a primary screening tool for cervical cancer in low health resources area.Therefore,careHPV could be the best screening strategy which is most suitable to the local communities.Part Ⅱ:2)CAIADS could assist junior colposcopist to improve the diagnostic accuracy and biopsy efficiency,which might be a promising solution to improve cervical cancer screening quality in low resource settings.Part Ⅱ:3)Immunohistochemical detection of HPV E7 protein was expected to be a new diagnostic method for the differential diagnosis of cervical lesions. |
PDF Full Text Request