human
***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 The human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine was immunogenic , generally well tolerated , and effective against HPV-16 or HPV-18 infections , and associated precancerous lesions in an event-triggered interim analysis of the phase III r and omised , double-blind , controlled PApilloma TRIal against Cancer In young Adults ( PATRICIA ) . We now assess the vaccine efficacy in the final event-driven analysis . METHODS Women ( 15 - 25 years ) were vaccinated at months 0 , 1 , and 6 . Analyses were done in the according-to- protocol cohort for efficacy ( ATP-E ; vaccine , n=8093 ; control , n=8069 ) , total vaccinated cohort ( TVC , included all women receiving at least one vaccine dose , regardless of their baseline HPV status ; represents the general population , including those who are sexually active ; vaccine , n=9319 ; control , n=9325 ) , and TVC-naive ( no evidence of oncogenic HPV infection at baseline ; represents women before sexual debut ; vaccine , n=5822 ; control , n=5819 ) . The primary endpoint was to assess vaccine efficacy against cervical intraepithelial neoplasia 2 + ( CIN2 + ) that was associated with HPV-16 or HPV-18 in women who were seronegative at baseline , and DNA negative at baseline and month 6 for the corresponding type ( ATP-E ) . This trial is registered with Clinical Trials.gov , number NCT00122681 . FINDINGS Mean follow-up was 34.9 months ( SD 6.4 ) after the third dose . Vaccine efficacy against CIN2 + associated with HPV-16/18 was 92.9 % ( 96.1 % CI 79.9 - 98.3 ) in the primary analysis and 98.1 % ( 88.4 - 100 ) in an analysis in which probable causality to HPV type was assigned in lesions infected with multiple oncogenic types ( ATP-E cohort ) . Vaccine efficacy against CIN2 + irrespective of HPV DNA in lesions was 30.4 % ( 16.4 - 42.1 ) in the TVC and 70.2 % ( 54.7 - 80.9 ) in the TVC-naive . Corresponding values against CIN3 + were 33.4 % ( 9.1 - 51.5 ) in the TVC and 87.0 % ( 54.9 - 97.7 ) in the TVC-naive . Vaccine efficacy against CIN2 + associated with 12 non-vaccine oncogenic types was 54.0 % ( 34.0 - 68.4 ; ATP-E ) . Individual cross-protection against CIN2 + associated with HPV-31 , HPV-33 , and HPV-45 was seen in the TVC . INTERPRETATION The HPV-16/18 AS04-adjuvanted vaccine showed high efficacy against CIN2 + associated with HPV-16/18 and non-vaccine oncogenic HPV types and substantial overall effect in cohorts that are relevant to universal mass vaccination and catch-up programmes . FUNDING GlaxoSmithKline Biologicals BACKGROUND Although the peak incidence of human papillomavirus ( HPV ) infection occurs in most population s within 5 - 10 years of first sexual experience , all women remain at risk for acquisition of HPV infections . We tested the safety , immunogenicity , and efficacy of the quadrivalent HPV ( types 6 , 11 , 16 , 18 ) L1 virus-like-particle vaccine in women aged 24 - 45 years . METHODS Women aged 24 - 45 years with no history of genital warts or cervical disease were enrolled from community health centres , academic health centres , and primary health-care providers into an ongoing multicentre , parallel , r and omised , placebo-controlled , double-blind study . Participants were allocated by computer-generated schedule to receive quadrivalent HPV vaccine ( n=1911 ) or placebo ( n=1908 ) at day 1 , and months 2 and 6 . All study site investigators and personnel , study participants , monitors , and central laboratory personnel were blinded to treatment allocation . Co primary efficacy endpoints were 6 months ' or more duration of infection and cervical and external genital disease due to HPV 6 , 11 , 16 , 18 ; and due to HPV 16 and 18 alone . Primary efficacy analyses were done in a per- protocol population , but intention-to-treat analyses were also undertaken . This study is registered with Clinical Trials.gov , number NCT00090220 . FINDINGS 1910 women received at least one dose of vaccine and 1907 at least one dose of placebo . In the per- protocol population , efficacy against the first co primary endpoint ( disease or infection related to HPV 6 , 11 , 16 , and 18 ) was 90.5 % ( 95 % CI 73.7 - 97.5 , four of 1615 cases in the vaccine group vs 41/1607 in the placebo group ) and 83.1 % ( 50.6 - 95.8 , four of 1601 cases vs 23/1579 cases ) against the second co primary endpoint ( disease or infection related to HPV 16 and 18 alone ) . In the intention-to-treat population , efficacy against the first co primary endpoint was 30.9 % ( 95 % CI 11.1 - 46.5 , 108/1886 cases vs 154/1883 cases ) and against the second co primary endpoint was 22.6 % ( -2.9 to 41.9 , 90/1886 cases vs 115/1883 cases ) , since infection and disease were present at baseline . We recorded no vaccine-related serious adverse events . INTERPRETATION The quadrivalent HPV vaccine is efficacious in women aged 24 - 45 years not infected with the relevant HPV types at enrolment . FUNDING Merck ( USA ) BACKGROUND A phase 3 trial was conducted to evaluate the efficacy of a prophylactic quadrivalent vaccine in preventing anogenital diseases associated with human papillomavirus ( HPV ) types 6 , 11 , 16 , and 18 . METHODS In this r and omized , placebo-controlled , double-blind trial involving 5455 women between the ages of 16 and 24 years , we assigned 2723 women to receive vaccine and 2732 to receive placebo at day 1 , month 2 , and month 6 . The co primary composite end points were the incidence of genital warts , vulvar or vaginal intraepithelial neoplasia , or cancer and the incidence of cervical intraepithelial neoplasia , adenocarcinoma in situ , or cancer associated with HPV type 6 , 11 , 16 , or 18 . Data for the primary analysis were collected for a per- protocol susceptible population of women who had no virologic evidence of HPV type 6 , 11 , 16 , or 18 through 1 month after administration of the third dose . RESULTS The women were followed for an average of 3 years after administration of the first dose . In the per- protocol population , those followed for vulvar , vaginal , or perianal disease included 2261 women ( 83 % ) in the vaccine group and 2279 ( 83 % ) in the placebo group . Those followed for cervical disease included 2241 women ( 82 % ) in the vaccine group and 2258 ( 83 % ) in the placebo group . Vaccine efficacy was 100 % for each of the co primary end points . In an intention-to-treat analysis , including those with prevalent infection or disease caused by vaccine-type and non-vaccine-type HPV , vaccination reduced the rate of any vulvar or vaginal perianal lesions regardless of the causal HPV type by 34 % ( 95 % confidence interval [ CI ] , 15 to 49 ) , and the rate of cervical lesions regardless of the causal HPV type by 20 % ( 95 % CI , 8 to 31 ) . CONCLUSIONS The quadrivalent vaccine significantly reduced the incidence of  HPV-associated anogenital diseases in young women . ( Clinical Trials.gov number , NCT00092521 [ Clinical Trials.gov ] . ) CONTEXT Viruslike particle human papillomavirus ( HPV ) vaccines were design ed to prevent HPV infection and development of cervical precancers and cancer . Women with oncogenic HPV infections might consider vaccination as therapy . OBJECTIVE To determine whether vaccination against HPV types 16 and 18 increases the rate of viral clearance in women already infected with HPV . DESIGN AND SETTING Phase 3 , masked , community-based r and omized trial conducted in 2 provinces of Costa Rica . PARTICIPANTS A total of 2189 women aged 18 to 25 years who were recruited between June 2004 and December 2005 . Participants were positive for HPV DNA at enrollment , had at least 6 months of follow-up , and had follow-up HPV DNA results . INTERVENTION Participants were r and omly assigned to receive 3 doses of a bivalent HPV-16/18 L1 protein viruslike particle AS04 c and i date vaccine ( n = 1088 ) or a control hepatitis A vaccine ( n = 1101 ) over 6 months . MAIN OUTCOME MEASURES Presence of HPV DNA was determined in cervical specimins by a molecular hybridization assay using chemiluminescence with HPV RNA probes and by polymerase chain reaction using SPF10 primers and a line probe assay detection system before vaccination and by polymerase chain reaction after vaccination . We compared rates of type-specific viral clearance using generalized estimating equations methods at the 6-month visit ( after 2 doses ) and 12-month visit ( after 3 doses ) in the 2 study groups . RESULTS There was no evidence of increased viral clearance at 6 or 12 months in the group who received HPV vaccine compared with the control group . Clearance rates for HPV-16/18 infections at 6 months were 33.4 % ( 82/248 ) in the HPV vaccine group and 31.6 % ( 95/298 ) in the control group ( vaccine efficacy for viral clearance , 2.5 % ; 95 % confidence interval , -9.8 % to 13.5 % ) . Human papillomavirus 16/18 clearance rates at 12 months were 48.8 % ( 86/177 ) in the HPV vaccine group and 49.8 % ( 110/220 ) in the control group ( vaccine efficacy for viral clearance , -2.0 % ; 95 % confidence interval , -24.3 % to 16.3 % ) . There was no evidence of a therapeutic effect for other oncogenic or nononcogenic HPV categories , among women receiving all vaccine doses , among women with single infections , or among women stratified by the following entry variables : HPV-16/18 serology , cytologic results , HPV DNA viral load , time since sexual debut , Chlamydia trachomatis or Neisseria gonorrhoeae infection , hormonal contraceptive use , or smoking . CONCLUSION In women positive for HPV DNA , HPV-16/18 vaccination does not accelerate clearance of the virus and should not be used to treat prevalent infections . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00128661 Human papillomavirus ( HPV ) causes cervical , vulvar , and vaginal cancers , precancerous dysplasia , and genital warts . We report data for the longest efficacy evaluation to date of a prophylactic HPV vaccine . In total , 552 women ( 16–23 years ) were enrolled in a r and omised , placebo-controlled study of a quadrivalent HPV 6/11/16/18 L1 virus-like-particle vaccine with vaccination at months 0 , 2 , and 6 . At regular intervals through 3 years , subjects underwent gynaecologic examination , cervicovaginal sampling for HPV DNA , serum anti-HPV testing , and Pap testing , with follow-up biopsy as indicated . A subset of 241 subjects underwent two further years of follow-up . At 5 years post enrolment , the combined incidence of HPV 6/11/16/18-related persistent infection or disease was reduced in vaccine-recipients by 96 % ( two cases vaccine versus 46 placebo ) . There were no cases of HPV 6/11/16/18-related precancerous cervical dysplasia or genital warts in vaccine recipients , 
    Output:
    
agent
***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 The human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine was immunogenic , generally well tolerated , and effective against HPV-16 or HPV-18 infections , and associated precancerous lesions in an event-triggered interim analysis of the phase III r and omised , double-blind , controlled PApilloma TRIal against Cancer In young Adults ( PATRICIA ) . We now assess the vaccine efficacy in the final event-driven analysis . METHODS Women ( 15 - 25 years ) were vaccinated at months 0 , 1 , and 6 . Analyses were done in the according-to- protocol cohort for efficacy ( ATP-E ; vaccine , n=8093 ; control , n=8069 ) , total vaccinated cohort ( TVC , included all women receiving at least one vaccine dose , regardless of their baseline HPV status ; represents the general population , including those who are sexually active ; vaccine , n=9319 ; control , n=9325 ) , and TVC-naive ( no evidence of oncogenic HPV infection at baseline ; represents women before sexual debut ; vaccine , n=5822 ; control , n=5819 ) . The primary endpoint was to assess vaccine efficacy against cervical intraepithelial neoplasia 2 + ( CIN2 + ) that was associated with HPV-16 or HPV-18 in women who were seronegative at baseline , and DNA negative at baseline and month 6 for the corresponding type ( ATP-E ) . This trial is registered with Clinical Trials.gov , number NCT00122681 . FINDINGS Mean follow-up was 34.9 months ( SD 6.4 ) after the third dose . Vaccine efficacy against CIN2 + associated with HPV-16/18 was 92.9 % ( 96.1 % CI 79.9 - 98.3 ) in the primary analysis and 98.1 % ( 88.4 - 100 ) in an analysis in which probable causality to HPV type was assigned in lesions infected with multiple oncogenic types ( ATP-E cohort ) . Vaccine efficacy against CIN2 + irrespective of HPV DNA in lesions was 30.4 % ( 16.4 - 42.1 ) in the TVC and 70.2 % ( 54.7 - 80.9 ) in the TVC-naive . Corresponding values against CIN3 + were 33.4 % ( 9.1 - 51.5 ) in the TVC and 87.0 % ( 54.9 - 97.7 ) in the TVC-naive . Vaccine efficacy against CIN2 + associated with 12 non-vaccine oncogenic types was 54.0 % ( 34.0 - 68.4 ; ATP-E ) . Individual cross-protection against CIN2 + associated with HPV-31 , HPV-33 , and HPV-45 was seen in the TVC . INTERPRETATION The HPV-16/18 AS04-adjuvanted vaccine showed high efficacy against CIN2 + associated with HPV-16/18 and non-vaccine oncogenic HPV types and substantial overall effect in cohorts that are relevant to universal mass vaccination and catch-up programmes . FUNDING GlaxoSmithKline Biologicals BACKGROUND Although the peak incidence of human papillomavirus ( HPV ) infection occurs in most population s within 5 - 10 years of first sexual experience , all women remain at risk for acquisition of HPV infections . We tested the safety , immunogenicity , and efficacy of the quadrivalent HPV ( types 6 , 11 , 16 , 18 ) L1 virus-like-particle vaccine in women aged 24 - 45 years . METHODS Women aged 24 - 45 years with no history of genital warts or cervical disease were enrolled from community health centres , academic health centres , and primary health-care providers into an ongoing multicentre , parallel , r and omised , placebo-controlled , double-blind study . Participants were allocated by computer-generated schedule to receive quadrivalent HPV vaccine ( n=1911 ) or placebo ( n=1908 ) at day 1 , and months 2 and 6 . All study site investigators and personnel , study participants , monitors , and central laboratory personnel were blinded to treatment allocation . Co primary efficacy endpoints were 6 months ' or more duration of infection and cervical and external genital disease due to HPV 6 , 11 , 16 , 18 ; and due to HPV 16 and 18 alone . Primary efficacy analyses were done in a per- protocol population , but intention-to-treat analyses were also undertaken . This study is registered with Clinical Trials.gov , number NCT00090220 . FINDINGS 1910 women received at least one dose of vaccine and 1907 at least one dose of placebo . In the per- protocol population , efficacy against the first co primary endpoint ( disease or infection related to HPV 6 , 11 , 16 , and 18 ) was 90.5 % ( 95 % CI 73.7 - 97.5 , four of 1615 cases in the vaccine group vs 41/1607 in the placebo group ) and 83.1 % ( 50.6 - 95.8 , four of 1601 cases vs 23/1579 cases ) against the second co primary endpoint ( disease or infection related to HPV 16 and 18 alone ) . In the intention-to-treat population , efficacy against the first co primary endpoint was 30.9 % ( 95 % CI 11.1 - 46.5 , 108/1886 cases vs 154/1883 cases ) and against the second co primary endpoint was 22.6 % ( -2.9 to 41.9 , 90/1886 cases vs 115/1883 cases ) , since infection and disease were present at baseline . We recorded no vaccine-related serious adverse events . INTERPRETATION The quadrivalent HPV vaccine is efficacious in women aged 24 - 45 years not infected with the relevant HPV types at enrolment . FUNDING Merck ( USA ) BACKGROUND A phase 3 trial was conducted to evaluate the efficacy of a prophylactic quadrivalent vaccine in preventing anogenital diseases associated with human papillomavirus ( HPV ) types 6 , 11 , 16 , and 18 . METHODS In this r and omized , placebo-controlled , double-blind trial involving 5455 women between the ages of 16 and 24 years , we assigned 2723 women to receive vaccine and 2732 to receive placebo at day 1 , month 2 , and month 6 . The co primary composite end points were the incidence of genital warts , vulvar or vaginal intraepithelial neoplasia , or cancer and the incidence of cervical intraepithelial neoplasia , adenocarcinoma in situ , or cancer associated with HPV type 6 , 11 , 16 , or 18 . Data for the primary analysis were collected for a per- protocol susceptible population of women who had no virologic evidence of HPV type 6 , 11 , 16 , or 18 through 1 month after administration of the third dose . RESULTS The women were followed for an average of 3 years after administration of the first dose . In the per- protocol population , those followed for vulvar , vaginal , or perianal disease included 2261 women ( 83 % ) in the vaccine group and 2279 ( 83 % ) in the placebo group . Those followed for cervical disease included 2241 women ( 82 % ) in the vaccine group and 2258 ( 83 % ) in the placebo group . Vaccine efficacy was 100 % for each of the co primary end points . In an intention-to-treat analysis , including those with prevalent infection or disease caused by vaccine-type and non-vaccine-type HPV , vaccination reduced the rate of any vulvar or vaginal perianal lesions regardless of the causal HPV type by 34 % ( 95 % confidence interval [ CI ] , 15 to 49 ) , and the rate of cervical lesions regardless of the causal HPV type by 20 % ( 95 % CI , 8 to 31 ) . CONCLUSIONS The quadrivalent vaccine significantly reduced the incidence of  HPV-associated anogenital diseases in young women . ( Clinical Trials.gov number , NCT00092521 [ Clinical Trials.gov ] . ) CONTEXT Viruslike particle human papillomavirus ( HPV ) vaccines were design ed to prevent HPV infection and development of cervical precancers and cancer . Women with oncogenic HPV infections might consider vaccination as therapy . OBJECTIVE To determine whether vaccination against HPV types 16 and 18 increases the rate of viral clearance in women already infected with HPV . DESIGN AND SETTING Phase 3 , masked , community-based r and omized trial conducted in 2 provinces of Costa Rica . PARTICIPANTS A total of 2189 women aged 18 to 25 years who were recruited between June 2004 and December 2005 . Participants were positive for HPV DNA at enrollment , had at least 6 months of follow-up , and had follow-up HPV DNA results . INTERVENTION Participants were r and omly assigned to receive 3 doses of a bivalent HPV-16/18 L1 protein viruslike particle AS04 c and i date vaccine ( n = 1088 ) or a control hepatitis A vaccine ( n = 1101 ) over 6 months . MAIN OUTCOME MEASURES Presence of HPV DNA was determined in cervical specimins by a molecular hybridization assay using chemiluminescence with HPV RNA probes and by polymerase chain reaction using SPF10 primers and a line probe assay detection system before vaccination and by polymerase chain reaction after vaccination . We compared rates of type-specific viral clearance using generalized estimating equations methods at the 6-month visit ( after 2 doses ) and 12-month visit ( after 3 doses ) in the 2 study groups . RESULTS There was no evidence of increased viral clearance at 6 or 12 months in the group who received HPV vaccine compared with the control group . Clearance rates for HPV-16/18 infections at 6 months were 33.4 % ( 82/248 ) in the HPV vaccine group and 31.6 % ( 95/298 ) in the control group ( vaccine efficacy for viral clearance , 2.5 % ; 95 % confidence interval , -9.8 % to 13.5 % ) . Human papillomavirus 16/18 clearance rates at 12 months were 48.8 % ( 86/177 ) in the HPV vaccine group and 49.8 % ( 110/220 ) in the control group ( vaccine efficacy for viral clearance , -2.0 % ; 95 % confidence interval , -24.3 % to 16.3 % ) . There was no evidence of a therapeutic effect for other oncogenic or nononcogenic HPV categories , among women receiving all vaccine doses , among women with single infections , or among women stratified by the following entry variables : HPV-16/18 serology , cytologic results , HPV DNA viral load , time since sexual debut , Chlamydia trachomatis or Neisseria gonorrhoeae infection , hormonal contraceptive use , or smoking . CONCLUSION In women positive for HPV DNA , HPV-16/18 vaccination does not accelerate clearance of the virus and should not be used to treat prevalent infections . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00128661 Human papillomavirus ( HPV ) causes cervical , vulvar , and vaginal cancers , precancerous dysplasia , and genital warts . We report data for the longest efficacy evaluation to date of a prophylactic HPV vaccine . In total , 552 women ( 16–23 years ) were enrolled in a r and omised , placebo-controlled study of a quadrivalent HPV 6/11/16/18 L1 virus-like-particle vaccine with vaccination at months 0 , 2 , and 6 . At regular intervals through 3 years , subjects underwent gynaecologic examination , cervicovaginal sampling for HPV DNA , serum anti-HPV testing , and Pap testing , with follow-up biopsy as indicated . A subset of 241 subjects underwent two further years of follow-up . At 5 years post enrolment , the combined incidence of HPV 6/11/16/18-related persistent infection or disease was reduced in vaccine-recipients by 96 % ( two cases vaccine versus 46 placebo ) . There were no cases of HPV 6/11/16/18-related precancerous cervical dysplasia or genital warts in vaccine recipients , 
    Output:
    