***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 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 To determine whether testing for DNA of oncogenic human papillomaviruses ( HPV ) is superior to the Papanicolaou ( Pap ) test for cervical-cancer screening , we conducted a r and omized trial comparing the two methods . METHODS We compared HPV testing , using an assay approved by the Food and Drug Administration , with conventional Pap testing as a screening method to identify high- grade cervical intraepithelial neoplasia in women ages 30 to 69 years in Montreal and St. John 's , Canada . Women with abnormal Pap test results or a positive HPV test ( at least 1 pg of high-risk HPV DNA per milliliter ) underwent colposcopy and biopsy , as did a r and om sample of women with negative tests . Sensitivity and specificity estimates were corrected for verification bias . RESULTS A total of 10,154 women were r and omly assigned to testing . Both tests were performed on all women in a r and omly assigned sequence at the same session . The sensitivity of HPV testing for cervical intraepithelial neoplasia of grade 2 or 3 was 94.6 % ( 95 % confidence interval [ CI ] , 84.2 to 100 ) , whereas the sensitivity of Pap testing was 55.4 % ( 95 % CI , 33.6 to 77.2 ; P=0.01 ) . The specificity was 94.1 % ( 95 % CI , 93.4 to 94.8 ) for HPV testing and 96.8 % ( 95 % CI , 96.3 to 97.3 ; P<0.001 ) for Pap testing . Performance was unaffected by the sequence of the tests . The sensitivity of both tests used together was 100 % , and the specificity was 92.5 % . Triage procedures for Pap or HPV testing result ed in fewer referrals for colposcopy than did either test alone but were less sensitive . No adverse events were reported . CONCLUSIONS As compared with Pap testing , HPV testing has greater sensitivity for the detection of cervical intraepithelial neoplasia . ( Current Controlled Trials number , IS RCT N57612064 [ controlled-trials.com ] . ) 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 Primary cervical screening with both human papillomavirus ( HPV ) DNA testing and cytological examination of cervical cells with a Pap test ( cytology ) has been evaluated in r and omized clinical trials . Because the vast majority of women with positive cytology are also HPV DNA positive , screening strategies that use HPV DNA testing as the primary screening test may be more effective . METHODS We used the data base from the intervention arm ( n = 6,257 women ) of a population -based r and omized trial of  double screening with cytology and HPV DNA testing to evaluate the efficacy of 11 possible cervical screening strategies that are based on HPV DNA testing alone , cytology alone , and HPV DNA testing combined with cytology  among women aged 32 - 38 years . The main outcome measures were sensitivity for detection of cervical intraepithelial neoplasia grade 3 or worse ( CIN3 + ) within 6 months of enrollment or at colposcopy for women with a persistent type-specific HPV infection and the number of screening tests and positive predictive value ( PPV ) for each screening strategy . All statistical tests were two-sided . RESULTS Compared with screening by cytology alone , double testing with cytology and for type-specific HPV persistence result ed in a 35 % ( 95 % confidence interval [ CI ] = 15 % to 60 % ) increase in sensitivity to detect CIN3 + , without a statistically significant reduction in the PPV ( relative PPV = 0.76 , 95 % CI = 0.52 to 1.10 ) , but with more than twice as many screening tests needed . Several strategies that incorporated screening for high-risk HPV subtypes were explored , but they result ed in reduced PPV compared with cytology . Compared with cytology , primary screening with HPV DNA testing followed by cytological triage and repeat HPV DNA testing of HPV DNA-positive women with normal cytology increased the CIN3 + sensitivity by 30 % ( 95 % CI = 9 % to 54 % ) , maintained a high PPV ( relative PPV = 0.87 , 95 % CI = 0.60 to 1.26 ) , and result ed in a mere 12 % increase in the number of screening tests ( from 6,257 to 7,019 tests ) . CONCLUSIONS Primary HPV DNA-based screening with cytology triage and repeat HPV DNA testing of cytology-negative women appears to be the most feasible cervical screening strategy Background : It has been suggested that adjustment for incomplete compliance with follow-up in women with positive human papillomavirus ( HPV ) tests would be appropriate for estimating the true sensitivity of cervical screening with HPV testing . We assessed the compliance and its impact on ⩾CIN3 detection in all eight r and omised controlled trials ( RCT ) with published baseline-round data . Methods : We extracted data on recommended follow-up procedures , follow-up compliance  , and ⩾CIN3 detection for both arms of each RCT , and assessed their correlation . Results : Compliance with a direct referral for colposcopy was around 90 % in all RCTs , whereas compliance with repeated testing among HPV-positive/cytology-negative women was around 60 % in three RCTs and 73 % in one RCT . Detection of ⩾CIN3 was significantly increased in two out of six RCTs with reported data . The correlation between compliance with follow-up in HPV-positive women and relative ⩾CIN3 detection was 0.48 ( P=0.33 ) . Conclusion : There is at present scant evidence to support the view that the measured sensitivity of HPV screening is a simple reflection of compliance with follow-up . Adjustment of measured cervical intraepithelial neoplasia detection on the basis of compliance data may not always be justifiable , and if adjustment is made , it should be used very judiciously BACKGROUND Tests for the DNA of high-risk types of human papillomavirus ( HPV ) have a higher sensitivity for cervical intraepithelial neoplasia grade 3 or worse ( CIN3 + ) than does cytological testing , but the necessity of such testing in cervical screening has been debated . Our aim was to determine whether the effectiveness of cervical screening improves when HPV DNA testing is implemented . METHODS Women aged 29 - 56 years who were participating in the regular cervical screening programme in the Netherl and s were r and omly assigned to combined cytological and HPV DNA testing or to conventional cytological testing only . After 5 years , combined cytological and HPV DNA testing were done in both groups . The primary outcome measure was the number of CIN3 + lesions detected . Analyses were done by intention to treat . This trial is registered as an International St and ard R and omised Controlled Trial , number IS RCT N20781131 . FINDINGS 8575 women in the intervention group and 8580 in the control group were recruited , followed up for sufficient time ( > or = 6.5 years ) , and met eligibility criteria for our analyses . More CIN3 + lesions were detected at baseline in the intervention group than in the control group ( 68/8575 vs 40/8580 , 70 % increase , 95 % CI 15 - 151 ; p=0.007 ) . The number of CIN3 + lesions detected in the subsequent round was lower in the intervention group than in the control group ( 24/8413 vs 54/8456 , 55 % decrease , 95 % CI 28 - 72 ; p=0.001 ) . The number of CIN3 + lesions over the two rounds did not differ between groups . INTERPRETATION The implementation of HPV DNA testing in cervical screening leads to earlier detection of CIN3 + lesions . Earlier detection of such lesions could permit an extension of the screening interval 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 
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Adverse effects of HPV testing were for both types of cytology setting s , generally higher for women below than above the age of 30 .
Adverse effects were less common among women aged at least 30 years than among younger women .
However , in older women HPV testing still led to more CIN1/CIN2 diagnoses and false-positive tests than cytology