***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: BACKGROUND Although testing for human papillomavirus ( HPV ) has higher sensitivity and lower specificity than cytology alone for detecting cervical intraepithelial neoplasia ( CIN ) , studies comparing conventional and liquid-based cytology have had conflicting results . METHODS In the first phase of a two-phase multicenter r and omized controlled trial , women aged 35 - 60 years in the conventional arm ( n = 16,658 ) were screened using conventional cytology , and women in the experimental arm ( n = 16,706 ) had liquid-based cytology  and were tested for high-risk HPV types using the Hybrid Capture 2 assay . Women in the conventional arm were referred to colposcopy with atypical cells of undetermined significance ( ASCUS ) or higher and those in the experimental arm were referred with ASCUS or higher cytology or with a positive ( > or = 1 pg/mL ) HPV test . Sensitivity and positive predictive value ( PPV ) for detection of cervical intraepithelial neoplasia grade 2 or higher ( CIN2 + ) were calculated . RESULTS The screening methods and referral criterion applied in the experimental arm had higher sensitivity than that in the conventional arm ( relative sensitivity = 1.47 ; 95 % confidence interval [ CI ] = 1.03 to 2.09 ) but a lower PPV ( relative PPV = 0.40 ; 95 % CI = 0.23 to 0.66 ) . With HPV testing alone at > or = 1 pg/mL and at > or = 2 pg/mL , the gain in sensitivity compared with the conventional arm remained similar ( relative sensitivity = 1.43 , 95 % CI = 1.00 to 2.04 and relative sensitivity = 1.41 , 95 % CI = 0.98 to 2.01 , respectively ) but PPV progressively improved ( relative PPV = 0.58 , 95 % CI = 0.33 to 0.98 and relative PPV = 0.75 , 95 % CI = 0.45 and 1.27 , respectively ) . Referral based on liquid-based cytology alone did not increase sensitivity compared with conventional cytology ( relative sensitivity = 1.06 ; 95 % CI = 0.72 to 1.55 ) but reduced PPV ( relative PPV = 0.57 ; 95 % CI = 0.39 to 0.82 ) . CONCLUSIONS HPV testing alone was more sensitive than conventional cytology among women 35 - 60 years old . Adding liquid-based cytology improved sensitivity only marginally but increased false-positives . HPV testing using Hybrid Capture 2 with a 2 pg/mL cutoff may be more appropriate than a 1 pg/mL cutoff for primary cervical cancer screening ABSTRACT R and omized trials have produced sound evidence about the efficacy of screening with human papillomavirus ( HPV ) DNA tests in reducing cervical cancer incidence and mortality . We evaluated the clinical performance and reproducibility of the Abbott RealTime High Risk ( HR ) HPV test compared with that of the HR hybrid capture 2 ( HC2 ) assay as assessed by a noninferiority score test . A r and om sample of 998 cervical specimens ( 914 specimens of cervical intraepithelial neoplasia less severe than grade 2 [ < CIN2 ] and 84 specimens of cervical intraepithelial neoplasia grade 2 or more severe lesions [ ≥CIN2 ] ) , collected in the Florence and Catania cervical Cancer Screening Programs from women aged 25 to 64 and already tested by HR HC2 , were retested with the Abbott RealTime HR HPV test . Absolute specificity was 92.3 % ( 95 % confidence interval [ CI ] , 90.4 to 94.0 ) and 92.6 % ( 95 % CI , 90.7 to 94.2 ) for the Abbott RealTime HR HPV test and the HR HC2 , respectively . Absolute sensitivity was 96.4 % ( 95 % CI , 89.9 to 99.3 ) and 97.6 % ( 95 % CI , 91.7 to 99.7 ) for the Abbott RealTime HR HPV test and the HR HC2 , respectively . The noninferiority score test revealed that the clinical sensitivity and specificity of the Abbott RealTime HR HPV test were not inferior ( P = 0.004 and 0.009 , respectively ) to those of HR HC2 . Overall agreement between the two assays was 96.5 % , with a k value of 0.86 ( CI 95 % , 0.82 to 0.91 ) . We evaluated the intralaboratory reproducibility by retesting 521 sample s at least 4 weeks after the first test ; the crude agreement between the first and second test was 98.5 % , with an overall k value of 0.97 ( CI 95 % , 0.95 to 0.99 ) . This test fully satisfies the requirements of a primary cervical cancer screening test . This assay differentiates between HPV16 , HPV18 , and non-HPV16/18 types in every specimen , but how to use this information in a screening setting still is unclear BACKGROUND Testing for human papillomavirus ( HPV ) DNA is reportedly more sensitive than cytology for the detection of high- grade cervical intraepithelial neoplasia ( CIN ) . The effectiveness of HPV testing in primary cervical screening was assessed in the ARTISTIC trial , which was done over two screening rounds approximately 3 years apart ( 2001 - 03 and 2004 - 07 ) by comparing liquid-based cytology ( LBC ) combined with HPV testing against LBC alone . METHODS Women aged 20 - 64 years who were undergoing routine screening as part of the English National Health Service Cervical Screening Programme in Greater Manchester were r and omly assigned ( between July , 2001 , and September , 2003 ) in a ratio of 3:1 to either combined LBC and HPV testing in which the results were revealed and acted on , or to combined LBC and HPV testing where the HPV result was concealed from the patient and investigator . The primary outcome was the detection rate of cervical intraepithelial neoplasia grade 3 or worse ( CIN3 + ) in the second screening round , analysed by intention to treat . This trial is registered with the International St and ard R and omised Controlled Trial Number IS RCT N25417821 . FINDINGS There were 24 510 eligible women at entry ( 18 386 in the revealed group , 6124 in the concealed group ) . In the first round of screening 233 women ( 1.27 % ) in the revealed group had CIN3 + , compared with 80 ( 1.31 % ) women in the concealed group ( odds ratio [ OR ] 0.97 , 95 % CI 0.75 - 1.25 ; p>0.2 ) . There was an unexpectedly large drop in the proportion of women with CIN3 + between the first and second rounds of screening in both groups , at 0.25 % ( 29 of 11 676 ) in the revealed group and 0.47 % ( 18 of 3866 women ) in the concealed group ( OR 0.53 , 95 % CI 0.30 - 0.96 ; p=0.042 ) . For both rounds combined , the proportion of women with CIN3 + were 1.51 % ( revealed ) and 1.77 % ( concealed ) ( OR 0.85 , 95 % CI 0.67 - 1.08 ; p>0.2 ) . INTERPRETATION LBC combined with HPV testing result ed in a significantly lower detection rate of CIN3 + in the second round of screening compared with LBC screening alone , but the effect was small . Over the two screening rounds combined , co-testing did not detect a higher rate of CIN3 + or CIN2 + than LBC alone . Potential changes in screening methodology should be assessed over at least two screening rounds . FUNDING National Institute of Health Research Health Technology Assessment Programme BACKGROUND Human papillomavirus ( HPV ) testing is more sensitive for the detection of high- grade cervical lesions than is cytology , but detection of HPV by DNA screening in two screening rounds 5 years apart has not been assessed . The aim of this study was to assess whether HPV DNA testing in the first screen decreases detection of cervical intraepithelial neoplasia ( CIN ) grade 3 or worse , CIN grade 2 or worse , and cervical cancer in the second screening . METHODS In this r and omised trial , women aged 29 - 56 years participating in the cervical screening programme in the Netherl and s were r and omly assigned to receive HPV DNA ( GP5+/6 + -PCR method ) and cytology co-testing or cytology testing alone , from January , 1999 , to September , 2002 . R and omisation ( in a 1:1 ratio ) was done with computer-generated r and om numbers after the cervical specimen had been taken . At the second screening 5 years later , HPV DNA and cytology co-testing was done in both groups ; research ers were masked to the patient 's assignment . The primary endpoint was the number of CIN grade 3 or worse detected . Analysis was done by intention to screen . The trial is now finished and is registered , number IS RCT N20781131 . FINDINGS 22,420 women were r and omly assigned to the intervention group and 22 518 to the control group ; 19 999 in the intervention group and 20,106 in the control group were eligible for analysis at the first screen . At the second screen , 19 579 women in the intervention group and 19,731 in the control group were eligible , of whom 16,750 and 16,743 , respectively , attended the second screen . In the second round , CIN grade 3 or worse was less common in the intervention group than in the control group ( 88 of 19 579 in the intervention group vs 122 of 19,731 in the control group ; relative risk 0·73 , 95 % CI 0·55 - 0·96 ; p=0·023 ) . Cervical cancer was also less common in the intervention group than in the control group ( four of 19 579 in the intervention group vs 14 of 19,731 ; 0·29 , 0·10 - 0·87 ; p=0·031 ) . In the baseline round , detection of CIN grade 3 or worse did not differ significantly between groups ( 171 of 19 999 vs 150 of 20,106 ; 1·15 , 0·92 - 1·43 ; p=0·239 ) but was significantly more common in women with normal cytology ( 34 of 19,286 vs 12 of 19,373 ; 2·85 , 1·47 - 5·49 ; p=0·001 ) . Furthermore , significantly more cases of CIN grade 2 or worse were detected in the intervention group than in the control group ( 267 of 19 999 vs 215 of 20,106 ; 1·25 , 1·05 - 1·50 ; p=0·015 ) . In the second screen , fewer HPV16-positive CIN grade 3 or worse were detected in the intervention group than in the control group ( 17 of 9481 vs 35 of 9354 ; 0·48 , 0·27 - 0·85 ; p=0·012 ) ; detection of non-HPV16-positive CIN grade 3 or worse did not differ between groups ( 25 of 9481 vs 25 of 9354 ; 0·99 , 0·57 - 1·72 ; p=1·00 ) . The cumulative detection of CIN grade 3 or worse and CIN grade 2 or worse did not differ significantly between study arms , neither for the whole study group ( CIN grade 3 or worse : 259 of 19 999 vs 272 of 20,106 ; 0·96 , 0·81 - 1·14 , p=0·631 ; CIN grade 2 or worse : 427 of 19 999 vs 399 of 20,106 ; 1·08 , 0·94 - 1·24 ; p=0·292 ) , nor for subgroups of women invited for the first time ( CIN grade 3 or worse in women aged 29 - 33 years : 102 of 3139 vs 105 of 3128 ; 0·97 , 0·74 - 1·27 ; CIN grade 2 or worse in women aged 29 - 33 years : 153 of 3139 vs 151 of 3128 ; 1·01 , 0·81 - 1·26 ; CIN grade 3 or worse in women aged 34 - 56 years : 157 of 16,860 vs 167 of 16 978 ; 0·95 , 0·7 
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Consistent evidence is available indicating that HPV-triage with the Hybrid Capture ( ® ) 2 assay ( Qiagen Gaithersburg , Inc. , MD , USA [ previously Digene Corp. ] ( HC2 ) is more accurate ( higher sensitivity , similar specificity ) than repeat cytology to triage women with equivocal Pap smear results .
Several other tests show at least similar accuracy but mRNA testing with the APTIMA ( ® ) ( Gen-Probe Inc. , San Diego , CA , USA ) test is similarly sensitive but more specific compared to HC2 .
In triage of low- grade squamous intraepithelial lesions ( LSIL ) , HC2 is more sensitive but its specificity is substantially lower compared to repeat cytology .
The APTIMA ( ® ) test is more specific than HC2 without showing a loss in sensitivity .
Identification of DNA of HPV types 16 and /or 18 , or RNA from the five most carcinogenic HPV types allow selecting women at highest risk for CIN3 + but the sensitivity and negative predictive value of these markers are lower than full-range high-risk HPV ( hrHPV ) testing .
After conservative treatment of cervical pre-cancer , HPV testing picks up more quickly , with higher sensitivity and not lower specificity , residual or recurrent high- grade CIN than follow-up cytology .
Primary screening for hrHPV generally detects more CIN2 , CIN3 or cancer compared to cytology at cut-off atypical squamous cells of undetermined significance ( ASC-US ) or LSIL , but is less specific .
Combined HPV and cytology screening provides a further small gain in sensitivity at the expense of a considerable loss in specificity if positive by either test is referred to colposcopy , in comparison with HPV testing only .
R and omised trials and follow-up of cohort studies consistently demonstrate a significantly lower cumulative incidence of CIN3 + and even of cancer , in women aged 30 years or older , who were at enrollment hrHPV DNA negative compared to those who were cytologically negative .
The difference in cumulative risk of CIN3 + or cancer for double negative ( cytology & HPV ) versus only HPV-negative women is small .
There exists a substantial evidence base to support that HPV testing is advantageous both in triage of women with equivocal abnormal cytology , in surveillance after treatment of CIN lesions and in primary screening of women aged 30 years or older .