| BackgroundPrimary HPV screening has been recommended as the preferred method for cervical cancer screening,but there is currently a lack of prospective cohort studies evaluating the effectiveness of various HPV detection techniques and HPV-based screening strategies at a population level,especially in low health resource areas.This study selected women who participated in cervical cancer screening in rural areas of Shanxi Province as an example to establish a screening cohort and evaluate the screening efficacy of new HPV detection technologies and different cervical cancer screening strategiesMaterials and MethodsSelected women who participated in rural "two-cancer screening" in Shangdang District and Wuxiang County of Changzhi City,Shanxi Province,established a 4-year cervical cancer screening cohort.In 2017,3,328 rural women in Shangdang District underwent cervical cancer screening using HPV fluorescence PCR technology;in 2018,3,913 rural women in Wuxiang County underwent cervical cancer screening using HPV microfluidic automatic nucleic acid detection technology(biochip method).All study subjects underwent baseline HPV and cytology screening.In the second and third years,cytological follow-up was performed for abnormal women based on the baseline year screening results.In the fourth year,HPV and cytology screening were performed for all study subjects.Abnormal women in the follow-up results were referred to colposcopy and underwent pathological examination if necessary.Using pathological diagnosis results as the gold standard,sensitivity(Se),specificity(Sp),positive predictive value(PPV),negative predictive value(NPV),etc.were calculated for different HPV detection technologies and triage strategies,as well as corresponding 95%confidence intervals(CI)and other indicators to evaluate the application effect of different HPV detection reagents and the screening effect of different screening strategies.Result1.Distribution of HPV infection among general women The demographic characteristics between two different HPV detection queues have good comparability.The HPV infection rates in the fluorescence PCR queue and the biological chip queue are 14.90%and 21.13%,respectively;with increasing age,pregnancy and childbirth times increase,and HPV infection rates increase(P<0.05);with increasing cultural level and age of first pregnancy,HPV infection rates show a downward trend(P<0.05);with increasing levels of cytology and pathology diagnosis of diseases,HPV infection rates show an increasing trend(P<0.05).The attribution risk of high-risk HPV in normal population is ranked from large to small as 52,16,58,51 and 56 types respectively.The attribution risk of high-risk HPV in CIN1 population is ranked from large to small as 16,52,58,66 and 31 types respectively,while that of CIN2+is ranked from large to small as 16,18,31,33 and 52 types respectively.2.Screening efficacy of two HPV testing cohort At baseline,the fluorescence PCR queue detected 38 cases of CIN2+,of which 36 were HPV positive and 2 were HPV negative;all the 26 cases of CIN2+detected by the biological chip queue were HPV positive;the fluorescence PCR queue detected a total of 53 CIN2+cases over four years,with 51 being HPV positive;the biological chip detected all the 54 CIN2+ cases and all were HPV positive.Regardless of baseline or cumulative data over four years,the sensitivity of HPV detection for CIN2+ in the biological chip queue was 100%,which was better than that in the fluorescence PCR queue(95.11%and 96.23%,χbaseline2=12.26,Pbseline<0.001;χcumulative2=7.24,Pcumulative-0.007).Moreover,the efficacy of diagnosing CIN2+with genotypes such as HPV16,HPV16/18 and HPV16/33 in the biological chip queue was also better than that in the fluorescence PCR queue.3.Evaluation of cervical cancer screening strategies for general population In the fluorescence PCR queue,at baseline,the sensitivity of screening out CIN2+ by HPV16/18(+)primary screening(94.74%)and combined screening strategy(97.37%)was higher than that by cytology primary screening(52.63%,χ2=1545.24,p<0.001),while the specificity,referral rate for colposcopy and NNR of HPV16/18(+)primary screening were better than those of combined screening(94.29%vs 87.22%,χ2=27.54,P<0.001;6.77%vs 13.78%,χ2=239.12,P<0.001;6.02 vs 11.95,χ2=195.69,P<0.001);when screening out CIN3+,both HPV16/18 primary screening and combined screening had a sensitivity of 100%,which was much higher than that by cytology screening(56.67%).Over four years,both HPV16/18(+)primary screening and combined screening strategy had higher sensitivity for screening out CIN2+than cytology primary screening(95.92%vs 48.00%,χ2=1595.56,P<0.001;97.96%vs 48.00%,χ2=1710.06,P<0.001).and both had a sensitivity of 100%for screening out CIN3+,which was also higher than that by cytology(56.67%,χ2=1198.37,P<0.001).The results in the biological chip queue showed a similar trend.4.Evaluation of triage algorithms in HPV positive women Sensitivity CIN2+of HPV positive women increased with the number of gene combinations,5hrHPV achieved the sensitivity of 97.22%,which was significantly higher than HPV16/18(80.56%)and HPV16(72.22%)in the HPV PCR cohort,while the specificity achieved opposite trends.The sensitivity of HPV16/33,16/52,16/58 were similar to that of HPV16/18,and all better than cytology triage.Conclusions1.HPV 52 and 58 were more common HPV infection types in normal and CIN1 populations;The sequence of type 18,31,and 33 was significantly advanced in CIN2+women;The risk of cervical lesions induced by type 18,31,and 33 could not be ignored,especially HPV18.2.Both fluorescence PCR detection technology and biological chip detection technology have good sensitivity and specificity;the screening efficacy of biological chip queue is slightly better than that of fluorescence PCR queue.In areas with limited healthcare resources and a lack of standardized HPV testing laboratories and workforce,HPV microfluidic automated nucleic acid detection technology based on biochip can be used.In areas with resourced laboratory conditions,traditional HPV detection techniques can be used to save the cost of purchasing equipment.3.The screening efficiency of the HPV primary screening and the combined primary screening strategies of HPV and cytology are similar,while the cytology primary screening strategy will reduce the screening efficiency.In the HPV primary screening strategy,different combinations of genotypes have different screening effects.HPV16/18(+)based screening strategy can be used as the preferred screening method in low-resource healthcare areas.4.Among HPV-positive women,an extended genotyping approach is recommended to replace cytology-based triage,and the triage effect of HPV16/33,HPV16/52,and HPV16/58 types cannot be ignored apart from HPV 16/18. |
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