***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 While many studies have compared the efficacy of Pap cytology , visual inspection with acetic acid ( VIA ) and human papillomavirus ( HPV ) DNA assays for the detection cervical intraepithelial neoplasia and cancer , few have evaluated the program effectiveness . Methods and Findings A population -based sample of 5603 women from Medchal M and al in And hra Pradesh , India were invited to participate in a study comparing Pap cytology , VIA , and HPV DNA screening for the detection of CIN3 + . Participation in primary screening and all subsequent follow-up visits was rigorously tracked . A 20 % r and om sample of all women screened , in addition to all women with a positive screening test result underwent colposcopy with directed biopsy for final diagnosis . Sensitivity , specificity , positive and negative predictive values were adjusted for verification bias . HPV testing had a higher sensitivity ( 100 % ) and specificity ( 90.6 % ) compared to Pap cytology ( sensitivity = 78.2 % ; specificity = 86.0 % ) and VIA ( sensitivity = 31.6 % ; specificity = 87.5 % ) . Since 58 % of the sample refused involvement and another 28 % refused colposcopy or biopsy , we estimated that potentially 87.6 % of the total underlying cases of CIN3 and cancer may have been missed due to program failures . Conclusions We conclude that despite our use of available re sources , infrastructure , and guidelines for cervical cancer screening implementation in re source limited areas , community participation and non-compliance remain the major obstacles to successful reduction in cervical cancer mortality in this Indian population .  HPV DNA testing  was both more sensitive and specific than Pap cytology  and VIA . The use of a less invasive and more user-friendly primary screening strategy ( such as self-collected swabs for HPV DNA testing ) may be required to achieve the coverage necessary for effective reduction in cervical cancer mortality 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 four r and omised trials , human papillomavirus (HPV)-based screening for cervical cancer was compared with cytology-based cervical screening , and precursors of cancer were the endpoint in every trial . However , direct estimates are missing of the relative efficacy of HPV-based versus cytology-based screening for prevention of invasive cancer in women who undergo regular screening , of modifiers ( eg , age ) of this relative efficacy , and of the duration of protection . We did a follow-up study of the four r and omised trials to investigate these outcomes . METHODS 176,464 women aged 20 - 64 years were r and omly assigned to HPV-based ( experimental arm ) or cytology-based ( control arm ) screening in Sweden ( Swedescreen ) , the Netherl and s ( POBASCAM ) , Engl and ( ARTISTIC ) , and Italy ( NTCC ) . We followed up these women for a median of 6·5 years ( 1,214,415 person-years ) and identified 107 invasive cervical carcinomas by linkage with screening , pathology , and cancer registries , by masked review of histological specimens , or from reports . Cumulative and study -adjusted rate ratios ( experimental vs control ) were calculated for incidence of invasive cervical carcinoma . FINDINGS The rate ratio for invasive cervical carcinoma among all women from recruitment to end of follow-up was 0·60 ( 95 % CI 0·40 - 0·89 ) , with no heterogeneity between studies ( p=0·52 ) . Detection of invasive cervical carcinoma was similar between screening methods during the first 2·5 years of follow-up ( 0·79 , 0·46 - 1·36 ) but was significantly lower in the experimental arm thereafter ( 0·45 , 0·25 - 0·81 ) . In women with a negative screening test at entry , the rate ratio was 0·30 ( 0·15 - 0·60 ) . The cumulative incidence of invasive cervical carcinoma in women with negative entry tests was 4·6 per 10(5 ) ( 1·1 - 12·1 ) and 8·7 per 10(5 ) ( 3·3 - 18·6 ) at 3·5 and 5·5 years , respectively , in the experimental arm , and 15·4 per 10(5 ) ( 7·9 - 27·0 ) and 36·0 per 10(5 ) ( 23·2 - 53·5 ) , respectively , in the control arm . Rate ratios did not differ by cancer stage , but were lower for adenocarcinoma ( 0·31 , 0·14 - 0·69 ) than for squamous-cell carcinoma ( 0·78 , 0·49 - 1·25 ) . The rate ratio was lowest in women aged 30 - 34 years ( 0·36 , 0·14 - 0·94 ) . INTERPRETATION HPV-based screening provides 60 - 70 % greater protection against invasive cervical carcinomas compared with cytology . Data of large-scale r and omised trials support initiation of HPV-based screening from age 30 years and extension of screening intervals to at least 5 years . FUNDING European Union , Belgian Foundation Against Cancer , KCE-Centre d'Expertise , IARC , The Netherl and s Organisation for Health Research and Development , the Italian Ministry of Health OBJECTIVE New commercial HPV RNA assays require further validation studies in population -based cervical cancer screening setting s. To assess the performance of ( FDA -approved ) APTIMA ® HPV Assay ( AHPV ) , Hybrid Capture 2 ( HC2 ) , in-house PCR genotyping , and ThinPrep LBC in population -based screening , stratified by three histological gold st and ards . STUDY DESIGN A multi-center trial in 5006 women undergoing routine screening in France was design ed to compare the absolute and relative risks of diagnosing CIN3 + and CIN2 + lesions by different diagnostic tests . RESULTS Reproducibility between the primary and second pathology reading was excellent for CIN3 + and CIN2 + endpoints ( Cohen 's kappa 0.948 and 0.854 ) . Absolute risks ( PPV ) of different tests ( AHPV , HC2 , PCR genotyping , LBC ) in diagnosing CIN2 + ( 15 - 20 % ) and CIN3 + ( 4 - 6 % ) were similar for the first , second , and consensus pathology readings . The relative risks of diagnosing these lesions by the four tests were also similar when the first , second or third pathology readings were employed . AHPV had the highest absolute risk of both histological endpoints , and detects 5 % to 15 % more CIN3 + and CIN2 + lesions , respectively , than LBC . Compared with HC2 assay , the relative risk of AHPV is 24 % to 29 % higher , with a significant difference in CIN2 + detection . With LBC as reference , AHPV had the best sensitivity/specificity balance measured by AUC ( area under ROC curve ) comparison test ( significant for CIN2 + ) , and the colposcopy referral rate ( 9.2 % ) comparable to that of LBC ( 8.7 % ) . CONCLUSIONS These data corroborate the suitability of AHPV for the 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 CONTEXT Human papillomaviruses ( HPVs ) are known to cause most cervical cancer worldwide , but the utility of HPV DNA testing in cervical cancer prevention has not been determined . OBJECTIVE To provide comprehensive data on the screening performance of HPV testing for the most common carcinogenic types , at different levels of analytic sensitivity . DESIGN Laboratory analysis conducted during 1993 - 1995 , using 3 cytologic techniques and cervicography , followed by colposcopic examination of women with any abnormal cervical finding , to detect all high- grade intraepithelial lesions and cancer ( reference st and ard of clinical ly significant disease ) . The HPV testing was performed subsequently with masking regarding clinical findings . SETTING Guanacaste Province , Costa Rica , a region with a high age-adjusted incidence of cervical cancer . PARTICIPANTS Of 117 
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Accuracy of HC2 was , however , greater in European countries compared to other countries .
Whilst HPV tests are less likely to miss cases of CIN 2 + and CIN 3 + , these tests do lead to more unnecessary referrals .
However , a negative HPV test is more reassuring than a negative cytological test , as the cytological test has a greater chance of being falsely negative , which could lead to delays in receiving the appropriate treatment .