***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 
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    Input: Background In the HPV FOCAL trial , we will establish the efficacy of hr-HPV DNA testing as a st and -alone screening test followed by liquid based cytology ( LBC ) triage of hr-HPV-positive women compared to LBC followed by hr-HPV triage with ≥ CIN3 as the outcome . Methods / Design HPV-FOCAL is a r and omized , controlled , three-armed study over a four year period conducted in British Columbia . It will recruit 33,000 women aged 25 - 65 through the province 's population based cervical cancer screening program . Control arm : LBC at entry and two years , and combined LBC and hr-HPV at four years among those with initial negative results and hr-HPV triage of ASCUS cases ; Two Year Safety Check arm : hr-HPV at entry and LBC at two years in those with initial negative results with LBC triage of hr-HPV positives ; Four Year Intervention Arm : hr-HPV at entry and combined hr-HPV and LBC at four years among those with initial negative results with LBC triage of hr-HPV positive cases Discussion To date , 6150 participants have a completed sample and epidemiologic question naire . Of the 2019 women enrolled in the control arm , 1908 ( 94.5 % ) were cytology negative . Women aged 25 - 29 had the highest rates of HSIL ( 1.4 % ) . In the safety arm 92.2 % of women were hr-HPV negative , with the highest rate of hr-HPV positivity found in 25 - 29 year old women ( 23.5 % ) . Similar results were obtained in the intervention arm HPV FOCAL is the first r and omized trial in North America to examine hr-HPV testing as the primary screen for cervical cancer within a population -based cervical cancer screening program . Trial Registration International St and ard R and omised Controlled Trial Number Register , IS RCT 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 BACKGROUND In the first recruitment phase of a r and omized trial of cervical cancer screening methods ( New Technologies for Cervical Cancer Screening [ NTCC ] study ) , we compared screening with conventional cytology with screening by human papillomavirus ( HPV ) testing in combination with liquid-based cytology .  HPV-positive women were directly referred to colposcopy if aged 35 or older ; if younger , they were retested after 1 year . METHODS In the second recruitment phase of NTCC , we r and omly assigned women to conventional cytology ( n = 24,661 ) with referral to colposcopy if cytology indicated atypical squamous cells of undetermined significance or more severe abnormality or to testing for high-risk HPV DNA alone by Hybrid Capture 2 ( n = 24,535 ) with referral to colposcopy if the test was positive at a concentration of HPV DNA 1 pg/mL or greater . For the main endpoint of the study , histologic detection of cervical intraepithelial neoplasia of grade 2 or more ( CIN2 + ) , we calculated and compared sensitivity and positive predictive value ( PPV ) of the two screening methods using HPV DNA cutoffs of 1 pg/mL and 2 pg/mL. All statistical tests were two-sided . RESULTS For women aged 35 - 60 years , the relative sensitivity of HPV testing for detection of CIN2 + at a cutoff of 1 pg/mL vs conventional cytology was 1.92 ( 95 % CI = 1.28 to 2.87 ) and the relative PPV was 0.80 ( 95 % CI = 0.55 to 1.18 ) . At a cutoff of 2 pg/mL HPV DNA , the relative sensitivity was 1.81 ( 95 % CI = 1.20 to 2.72 ) and the relative PPV was 0.99 ( 95 % CI = 0.67 to 1.46 ) . In this age group , there was no evidence of heterogeneity between study phases . Among women aged 25 - 34 years , the relative sensitivity for detection of CIN2 + of HPV testing at a cutoff of 1 pg/mL vs cytology was 3.50 ( 95 % CI = 2.11 to 5.82 ) , statistically significantly larger ( P = .019 ) than that observed in phase 1 at this age ( 1.58 ; 95 % CI = 1.03 to 2.44 ) . CONCLUSIONS For women aged 35 - 60 years , HPV testing with a cutoff of 2 pg/mL achieves a substantial gain in sensitivity over cytology with only a small reduction in PPV . Among women aged 25 - 34 years , the large relative sensitivity of HPV testing compared with conventional cytology and the difference between relative sensitivity during phases 1 and 2 suggests that there is frequent regression of CIN2 + that are detected by direct referral of younger HPV-positive women to colposcopy . Thus , triage test or repeat testing is needed if HPV is to be used for primary testing in this context CONTEXT Non-cytology-based screen- and -treat approaches for cervical cancer prevention have been developed for low-re source setting s , but few have directly addressed efficacy . OBJECTIVE To determine the safety and efficacy of 2 screen- and -treat approaches for cervical cancer prevention that were design ed to be more re source -appropriate than conventional cytology-based screening programs . DESIGN , SETTING , AND PATIENTS R and omized clinical trial of 6555 nonpregnant women , aged 35 to 65 years , recruited through community outreach and conducted between June 2000 and December 2002 at ambulatory women 's health clinics in Khayelitsha , South Africa . INTERVENTIONS All patients were screened using human papillomavirus ( HPV ) DNA testing and visual inspection with acetic acid ( VIA ) . Women were subsequently r and omized to 1 of 3 groups : cryotherapy if she had a positive HPV DNA test result ; cryotherapy if she had a positive VIA test result ; or to delayed evaluation . MAIN OUTCOME MEASURES Biopsy-confirmed high- grade cervical cancer precursor lesions and cancer at 6 and 12 months in the HPV DNA and VIA groups compared with the delayed evaluation ( control ) group ; complications after cryotherapy . RESULTS The prevalence of high- grade cervical intraepithelial neoplasia and cancer ( CIN 2 + ) was significantly lower in the 2 screen- and -treat groups at 6 months after r and omization than in the delayed evaluation group . At 6 months , CIN 2 + was diagnosed in 0.80 % ( 95 % confidence interval [ CI ] , 0.40%-1.20 % ) of the women in the HPV DNA group and 2.23 % ( 95 % CI , 1.57%-2.89 % ) in the VIA group compared with 3.55 % ( 95 % CI , 2.71%-4.39 % ) in the delayed evaluation group ( P<.001 and P = .02 for the HPV DNA and VIA groups , respectively ) . A subset of women underwent a second colposcopy 12 months after enrollment . At 12 months the cumulative detection of CIN 2 + among women in the HPV DNA group was 1.42 % ( 95 % CI , 0.88%-1.97 % ) , 2.91 % ( 95 % CI , 2.12%-3.69 % ) in the VIA group , and 5.41 % ( 95 % CI , 4.32%-6.50 % ) in the delayed evaluation group . Although minor complaints , such as discharge and bleeding , were common after cryotherapy , major complications were rare . CONCLUSION Both screen- and -treat approaches are safe and result in a lower prevalence of high- grade cervical cancer precursor lesions compared with delayed evaluation at both 6 and 12 months . Trial Registration http:// clinical trials.gov Identifier : NCT00233727 OBJECTIVES Primary cervical screening uses cytology to detect cancer precursor lesions [ cervical intraepithelial neoplasia stage 3 or beyond ( CIN3 + ) ] . Human papillomavirus ( HPV ) testing could add sensitivity as an adjunct to cytology or as a first test , reserving cytology for HPV-positive women . This study addresses the questions : Does the combination of cytology and HPV testing achieve a reduction in incident CIN3 + ? ; Is HPV testing cost-effective in primary cervical screening ? ; Is its use associated with adverse psychosocial or psychosexual effects ? ; and How would it perform as an initial screening test followed by cytology for HPV positivity ? DESIGN ARTISTIC was a r and omised trial of cervical cytology versus cervical cytology plus HPV testing , evaluated over two screening rounds , 3 years apart . Round 1 would detect prevalent disease and round 2 a combination of incident and undetected disease from round 1 . SETTING Women undergoing routine cervical screening in the NHS programme in Greater Manchester . PARTICIPANTS In total 24,510 women aged 20 - 64 years were enrolled between July 2001 and September 2003 . INTERVENTIONS HPV testing was performed on the liquid-based cytology ( LBC ) sample obtained at screening . Women were r and omised in a ratio of 3:1 to have the HPV test result revealed and acted upon if persistently positive in cytology-negative cases or concealed . A detailed health economic evaluation and a psychosocial and psychosexual assessment were also performed . MAIN OUTCOME MEASURES The primary outcome was CIN3 + in round 2 . Secondary outcomes included an economic assessment and psychosocial effects . A large HPV genotyping study was also conducted . RESULTS In round 1 there were 313 CIN3 + lesions , representing a prevalence in the revealed and concealed arms of 1.27 % and 1.31 % respectively ( p = 0.81 ) . Round 2 ( 30 - 48 months ) involved 14,230 ( 58.1 % ) of the women screened in round 1 and only 31 CIN3 + were detected ; the CIN3 rate was not significantly different between the revealed and concealed arms . A less restrictive definition of round 2 ( 26 - 54 months ) increased CIN3 + to 45 and CIN3 + incidence in the arms was significantly different ( p = 0.05 ) . There was no difference in CIN3 + between the arms when rounds 1 and 2 were combined . Prevalence of high-risk HPV types was age-dependent . Overall prevalence of HPV16/18 increased with severity of dyskaryosis . Mean costs per woman in round 1 were 
    Output:
    
Although the data were derived from the baseline screening rounds only , the decrease in the sensitivity for high grade cervical intraepithelial neoplasia using a hybrid capture 2 cut-off level between ≥ 2 rlu/co and ≥ 10 rlu/co seemed acceptable given the international recommendations for testing for human papillomavirus DNA in cervical screening , which require 90 % or more sensitivity for cervical intraepithelial neoplasia grade II or higher compared with hybrid capture 2 at ≥ 1 rlu/co .
The data suggest that the hybrid capture 2 cut-off level could be increased in primary screening ; this seems reasonably safe and is significantly less burdensome for women