***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: We prospect ively evaluated the 5-year predictive values of adding high-risk human papillomavirus ( hrHPV ) testing to cytology for the detection of ⩾cervical intraepithelial neoplasia (CIN)3 lesions in a population -based cohort of 2810 women . At baseline , nine ( 0.3 % ) women had prevalent lesions ⩾CIN3 , all being hrHPV positive . After 5 years of follow-up , four ( 6.5 % ) of the 62 hrHPV-positive women with normal cytology developed lesions ⩾CIN3 , vs only one ( 0.05 % ) of the 2175 hrHPV-negative women with normal cytology . High-risk human papillomavirus testing or combined screening revealed a much higher sensitivity , at the cost of a small decrease in specificity , and a higher negative predictive value for the detection of lesions ⩾CIN3 till the next screening round ( 5 years ) than cytology alone Cervical intraepithelial neoplasia 3 ( CIN3 ) is the precursor of mostsquamous carcinomas and serves as a surrogate end point . However , small CIN3 lesions are rarely associated with concurrent invasion . We hypothesized that aggressive follow-up for cytology of atypical squamous cells of undetermined significance ( ASCUS ) or low- grade squamous intraepithelial lesion ( LSIL ) leads predominantly to detection of smaller CIN3 lesions than those usually associated with cancer . We assessed this hypothesis in a masked histopathologic review of 330 CIN3 lesions in the ASCUS LSILTriage Study , focusing on ASCUS referrals . ASCUS referrals underwent r and omized management [ colposcopy for repeat cytology of high- grade squamous intraepithelial lesion ( HSIL ) , colposcopy for oncogenic human papillomavirus ( HPV ) detection or repeat HSIL , or immediate colposcopy ] ; then all were followed with repeat cytology for 2 years , followed by colposcopy and aggressive treatment . We assessed all CIN3 lesions qualitatively and measured 39 of them . CIN3 lesions were overwhelmingly small . Compared with enrollment , lesions found at follow-up or exit involved fewer tissue fragments ( P < 0.01 ) and showed less diffuse gl and involvement ( P = 0.03 ) . CIN3 lesions found postenrollment after HPV testing involved the fewest tissue fragments [ versus immediate colposcopy ( P = 0.04 ) or repeat cytology of HSIL ( P = 0.02 ) ] , and none showed diffuse gl and involvement . The median distal-proximal length was 6.5 mm ( median replacement of total epithelium = 5 % ) in the 39 measured cases . We conclude that CIN3 lesions underlying ASCUS or LSIL generally lack features associated with invasion , particularly if managed using HPV testing , suggesting that aggressive management leads to early detection of CIN3 but probably prevents relatively few cancers in screened population Objective To evaluate the efficiency of human papillomavirus ( HPV ) testing by Hybrid Capture II ( Digene Diagnostics Inc. , Silver Spring , MD ) with regard to detecting biopsyconfirmed cervical intraepithelial neoplasia ( CIN ) or high- grade CIN in women with mild atypia , compared with the efficiencies of polymerase chain reaction ( PCR ) , Southern blot hybridization , and cytology . Methods We prospect ively studied 378 women with atypical squamous cells of undetermined significance ( ASCUS ) ( n = 111 ) or low- grade squamous intraepithelial lesions ( SILs ) ( n = 267 ) demonstrated by referral cytology . We did repeat cytology , sampling for detection of HPV DNA by Hybrid Capture II , PCR , and Southern blot hybridization , and colposcopic evaluation with cervical biopsies . Results All participants underwent the Hybrid Capture II test and 320 underwent the three HPV tests .  Sensitivities of  Hybrid Capture II for detecting CIN and high- grade CIN ( 0.81 and 0.86 , respectively ) were similar to those of cytology ( 0.83 and 0.82 , respectively ) and PCR ( 0.77 and 0.95 , respectively ) , and higher than those of Southern blot hybridization ( 0.48 and 0.45 , respectively ) . Compared with cytology , combined triage with Hybrid Capture II improved sensitivities for detecting CIN ( 0.94 versus 0.83 , P < .001 ) and high- grade CIN ( 0.96 versus 0.85 ) , though the latter difference was not significant ( P = .17 ) . In women with ASCUS , sensitivities of combined triage and cytology for detecting CIN were 0.94 and 0.71 , respectively ( P = .01 ) , and sensitivities of the two methods for detecting high- grade CIN were 0.92 and 0.66 , respectively ( P = .13 ) . The increase in sensitivity was lower among women with low- grade SILs ; for these women , cytology had high sensitivity ( 0.86 for CIN and 1.00 for high- grade CIN ) . The specificity of combined triage was significantly lower than that of cytology in both groups . Conclusion Compared with repeat cytology , combined triage with HPV testing markedly improves sensitivity for detecting CIN in women with ASCUS , but at the expense of specificity We evaluated Hybrid Capture 2 ( HC2 ) and polymerase chain reaction ( PCR ) results for paired specimens collected at 19,187 visits from 5,026 of 5,060 women participating in the Atypical Squamous Cells of Undetermined Significance /Low- Grade Squamous Intraepithelial Lesion Triage Study ( ALTS ) . We examined the test agreement between HC2 and PCR detection for any of 13 carcinogenic human papillomavirus types targeted by HC2 and compared clinical performance of the 2 tests for detecting concurrent and follow-up cervical intraepithelial neoplasia ( CIN ) 3 or cancer . The k value for the 2 assays was 0.65 ( 95 % confidence interval , 0.64 - 0.66 ) , with 82.7 % crude agreement . HC2 was more sensitive ( 93.6 % vs 89.3 % ; P < .0005 ) but less specific ( 41.2 % vs 48.5 % ; P < .0005 ) than PCR for detecting 2-year cumulative CIN 3 or cancer ( n = 503 ) . The presence of multiple types as detected by PCR and /or cytologic abnormality increased the likelihood of an HC2 + result . Increased sensitivity of HC2 compared with PCR was surprising , given the theoretical advantages of PCR-based methods for analytic sensitivity . Smaller amounts of material used in PCR could have limited its sensitivity , but our results demonstrate the importance of optimization and st and ardization of PCR-based assays for clinical applications BACKGROUND Human papillomavirus ( HPV ) testing is known to be more sensitive , but less specific than cytology for detecting cervical intraepithelial neoplasia ( CIN ) . We assessed the efficacy of cervical-cancer screening policies that are based on HPV testing . METHODS Between March , 2004 , and December , 2004 , in two separate recruitment phases , women aged 25 - 60 years were r and omly assigned to conventional cytology or to HPV testing in combination with liquid-based cytology ( first phase ) or alone ( second phase ) . R and omisation was done by computer in two screening centres and by sequential opening of numbered sealed envelopes in the remaining seven centres . During phase one , women who were HPV-positive and aged 35 - 60 years were referred to colposcopy , whereas women aged 25 - 34 years were referred to colposcopy only if cytology was also abnormal or HPV testing was persistently positive . During phase two , women in the HPV group were referred for colposcopy if the HPV test was positive . Two rounds of screening occurred in each phase , and all women had cytology testing only at the second round . The primary endpoint was the detection of grade 2 and 3 CIN , and of invasive cervical cancers during the first and second screening rounds . Analysis was done by intention to screen . This trial is registered , number IS RCT N81678807 . FINDINGS In total for both phases , 47,001 women were r and omly assigned to the cytology group and 47,369 to HPV testing . 33,851 women from the cytology group and 32,998 from the HPV-testing group had a second round of screening . We also retrieved the histological diagnoses from screening done elsewhere . The detection of invasive cervical cancers was similar for the two groups in the first round of screening ( nine in the cytology group vs seven in the HPV group , p=0.62 ) ; no cases were detected in the HPV group during round two , compared with nine in the cytology group ( p=0.004 ) . Overall , in the two rounds of screening , 18 invasive cancers were detected in the cytology group versus seven in the HPV group ( p=0.028 ) . Among women aged 35 - 60 years , at round one the relative detection ( HPV vs cytology ) was 2.00 ( 95 % CI 1.44 - 2.77 ) for CIN2 , 2.08 ( 1.47 - 2.95 ) for CIN3 , and 2.03 ( 1.60 - 2.57 ) for CIN2 and 3 together . At round two the relative detection was 0.54 ( 0.23 - 1.28 ) for CIN2 , 0.48 ( 0.21 - 1.11 ) for CIN3 , and 0.51 ( 0.28 - 0.93 ) for CIN2 and 3 together . Among women aged 25 - 34 years , there was significant heterogeneity between phases in the relative detection of CIN3 . At round one the relative detection was 0.93 ( 0.52 - 1.64 ) in phase one and 3.91 ( 2.02 - 7.57 ) in phase two . At round two the relative detection was 1.34 ( 0.46 - 3.84 ) in phase one and 0.20 ( 0.04 - 0.93 ) in phase two . Pooling both phases , the detection ratio of CIN2 for women aged 25 - 34 years was 4.09 ( 2.24 - 7.48 ) at round one and 0.64 ( 0.23 - 1.27 ) at round two . INTERPRETATION HPV-based screening is more effective than cytology in preventing invasive cervical cancer , by detecting persistent high- grade lesions earlier and providing a longer low-risk period . However , in younger women , HPV screening leads to over-diagnosis of regressive CIN2 . FUNDING European Union , Italian Ministry of Health , Regional Health Administrations of Piemonte , Tuscany , Veneto and Emilia-Romagna , and Public Health Agency of Lazio ABSTRACT The use of high-risk human papillomavirus ( hrHPV ) testing as an adjunct to cervical cytology in population -based screening programs is currently based on DNA hybridization and PCR assays . The aim of this study was to prospect ively assess the diagnostic performance of the Hybrid Capture 2 test ( HC2 ; Digene Corporation ) in comparison with that of the recently developed PCR-based AMPLICOR HPV test ( Roche Molecular Systems ) for the detection of 13 hrHPV types . A reverse line blot hybridization assay ( Innogenetics ) was used as an internal reference st and ard in discordant cases . Two hundred seventy-one patients with atypical squamous cells of uncertain significance ( ASCUS ) in cervical sample s underwent hrHPV testing .  The chi-square test was performed to compare respective proportions . Totals of 160/271 ( 59 % ) and 156/271 ( 58 % ) were found to be positive for hrHPV with HC2 and AMPLICOR , respectively . Concordant results were obtained for 235 ( 86.7 % ) of the 271 sample s ( kappa statistic , 0.73 ± 0.04 ) . Considering types 26 , 53 , and 66 as oncogenic types , negative predictive values ( NPVs ) of HC2 and AMPLICOR were 92.8 % and 87.8 % , respectively ( difference was not significant ) , and their respective accuracies were 94.8 % and 91.9 % ( difference was not significant ) . Considering types 26 , 53 , and 66 as not oncogenic , the respective HC2 and AMPLICOR NPVs were 92.8 % and 97.4 % ( difference was not significant ) , and accuracy was significantly higher for the AMPLICOR assay ( 95.9 % versus 90.8 % for HC2 ) ( P < 0.05 ) . For ASCUS sample s , the NPV was 92.8 % for HC2 testing and might be compromised if the copy number of HPV DNA was low . The NPV was 97.4 % for the AMPLICOR assay and might be compromised if HPV types 26 ,  
    Output:
    
Based on higher test accuracy , our results support the use of HCII in cervical cancer screening programs .