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 : Previous analyses from a r and omised trial in women aged 24–45 years have shown the quadrivalent human papillomavirus ( qHPV ) vaccine to be efficacious in the prevention of infection , cervical intraepithelial neoplasia ( CIN ) , and external genital lesions ( EGLs ) related to HPV 6/11/16/18 . In this report , we present end-of- study efficacy , safety , and immunogenicity data with a median follow-up time of 4.0 years . Methods : We enrolled 3819 24–45-year-old women with no history of cervical disease or genital warts in the past 5 years . Women received quadrivalent vaccine or placebo at day 1 , and at months 2 and 6 . Ascertainment of CIN/EGL was accomplished through Pap testing , genital inspection , and cervicovaginal sampling ( every 6 months ) . The main analysis was conducted in a per- protocol efficacy population ( that received three doses , was naive to the relevant HPV types at day 1 , and remained free of infection through month 7 ) . Efficacy was also estimated in other naive and non-naive population s. Results : Vaccine efficacy against the combined incidence of persistent infection , CIN/EGL related to HPV6/11/16/18 in the per- protocol population was 88.7 % ( 95 % CI : 78.1 , 94.8 ) . Efficacy for women who were seropositive and DNA negative for the relevant vaccine HPV type at the time of enrolment who received at least 1 dose was 66.9 % ( 95 % CI : 4.3 , 90.6 ) . At month 48 , 91.5 , 92.0 , 97.4 , and 47.9 % of vaccinated women were seropositive to HPV 6/11/16/18 , respectively . No serious vaccine-related adverse experiences were reported . Conclusions : The qHPV vaccine demonstrated high efficacy , immunogenicity , and acceptable safety in women aged 24–45 years , regardless of previous exposure to HPV vaccine type Background . Cervical cancer is a major public health problem for women in sub-Saharan Africa . Availability of a human papillomavirus ( HPV ) vaccine could have an important public health impact . Methods . In this phase IIIb , double-blind , r and omized , placebo-controlled , multicenter trial ( NCT00481767 ) , healthy African girls and young women seronegative for human immunodeficiency virus ( HIV ) were stratified by age ( 10–14 or 15–25 years ) and r and omized ( 2:1 ) to receive either HPV-16/18 AS04-adjuvanted vaccine ( n = 450 ) or placebo ( n = 226 ) at 0 , 1 , and 6 months . The primary objective was to evaluate HPV-16/18 antibody responses at month 7 . Seropositivity rates and corresponding geometric mean titers ( GMTs ) were measured by enzyme-linked immunosorbent assay . Results . In the according-to- protocol analysis at month 7 , 100 % of initially seronegative participants in the vaccine group were seropositive for both anti – HPV-16 and anti – HPV-18 antibodies ( n = 130 and n = 128 for 10–14-year-olds , respectively ; n = 190 and n = 212 for 15–25-year-olds ) . GMTs for HPV-16 and HPV-18 were higher in 10–14-year-olds ( 18 423 [ 95 % confidence interval , 16 185–20 970 ] and 6487 [ 5590–7529 ] enzyme-linked immunosorbent assay units (EU)/mL , respectively ) than in 15–25-year-olds ( 10 683 [ 9567–11 930 ] and 3743 [ 3400–4120 ] EU/mL , respectively ) . Seropositivity was maintained at month 12 . No participant withdrew owing to adverse events . No vaccine-related serious adverse events were reported . Conclusions . The HPV-16/18 AS04-adjuvanted vaccine was highly immunogenic and had a clinical ly acceptable safety profile when administered to healthy HIV-seronegative African girls and young women Control of human papillomavirus (HPV)-related cancers by inclusion of HPV vaccination into national vaccination programmes is likely . One open question is replacement of the vaccine types with other high-risk ( hr ) HPV types in the vaccination era . We studied occurrence of HPV types in adolescent females participating in a population -based vaccination trial . A total of 4,808 16- to 17-year-old females from Finl and were enrolled in the 1:1 r and omized phase III ( PATRICIA ) trial of the efficacy of vaccination with the  AS04-adjuvanted HPV-16/18 virus-like particle vaccine as compared to hepatitis A virus ( HAV ) vaccine .  HPV infection was assessed from cervical sample s taken every 6 months for 4 years post-vaccination by polymerase chain reaction ( PCR ) for genital oncogenic HPV types 16 , 18 , 31 , 33 , 35 , 39 , 45 , 51 , 52 , 58 , 59 , 66 , 68 , and 73 as well as low-risk types HPV-6 and HPV-11 . The  HPV-16/18 vaccine coverage ranged between 1 and 22 % by age-cohort and study community . Odds ratios ( ORs ) for infections with different HPV types in baseline PCR negative HPV-16/18 vs. HAV vaccinated women , and Poisson regression derived HPV incidence rate ratios ( IRRs ) in baseline positive vs. negative women were calculated . The OR and IRR estimates for acquisition of any genital HPV types showed no excess risk neither in baseline HPV DNA-negative HPV-16/18-vaccinated women compared to baseline HPV DNA-negative HAV vaccinated women nor in HPV-16/18-vaccinated baseline HPV-16/18-positive women compared to baseline HPV-16/18-negative women . In the HAV-vaccinated , baseline HPV-18-positive women showed an increased risk of acquiring other clade A7 HPV types ( 39 , 45 , 59 , 68 ) ( IRR 1.8 , 95 % confidence interval = 1.01.-3.1 ) . We found no increased occurrence of non-vaccine HPV types suggestive of type-replacement 1 - 4 years post- 
    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 : Previous analyses from a r and omised trial in women aged 24–45 years have shown the quadrivalent human papillomavirus ( qHPV ) vaccine to be efficacious in the prevention of infection , cervical intraepithelial neoplasia ( CIN ) , and external genital lesions ( EGLs ) related to HPV 6/11/16/18 . In this report , we present end-of- study efficacy , safety , and immunogenicity data with a median follow-up time of 4.0 years . Methods : We enrolled 3819 24–45-year-old women with no history of cervical disease or genital warts in the past 5 years . Women received quadrivalent vaccine or placebo at day 1 , and at months 2 and 6 . Ascertainment of CIN/EGL was accomplished through Pap testing , genital inspection , and cervicovaginal sampling ( every 6 months ) . The main analysis was conducted in a per- protocol efficacy population ( that received three doses , was naive to the relevant HPV types at day 1 , and remained free of infection through month 7 ) . Efficacy was also estimated in other naive and non-naive population s. Results : Vaccine efficacy against the combined incidence of persistent infection , CIN/EGL related to HPV6/11/16/18 in the per- protocol population was 88.7 % ( 95 % CI : 78.1 , 94.8 ) . Efficacy for women who were seropositive and DNA negative for the relevant vaccine HPV type at the time of enrolment who received at least 1 dose was 66.9 % ( 95 % CI : 4.3 , 90.6 ) . At month 48 , 91.5 , 92.0 , 97.4 , and 47.9 % of vaccinated women were seropositive to HPV 6/11/16/18 , respectively . No serious vaccine-related adverse experiences were reported . Conclusions : The qHPV vaccine demonstrated high efficacy , immunogenicity , and acceptable safety in women aged 24–45 years , regardless of previous exposure to HPV vaccine type Background . Cervical cancer is a major public health problem for women in sub-Saharan Africa . Availability of a human papillomavirus ( HPV ) vaccine could have an important public health impact . Methods . In this phase IIIb , double-blind , r and omized , placebo-controlled , multicenter trial ( NCT00481767 ) , healthy African girls and young women seronegative for human immunodeficiency virus ( HIV ) were stratified by age ( 10–14 or 15–25 years ) and r and omized ( 2:1 ) to receive either HPV-16/18 AS04-adjuvanted vaccine ( n = 450 ) or placebo ( n = 226 ) at 0 , 1 , and 6 months . The primary objective was to evaluate HPV-16/18 antibody responses at month 7 . Seropositivity rates and corresponding geometric mean titers ( GMTs ) were measured by enzyme-linked immunosorbent assay . Results . In the according-to- protocol analysis at month 7 , 100 % of initially seronegative participants in the vaccine group were seropositive for both anti – HPV-16 and anti – HPV-18 antibodies ( n = 130 and n = 128 for 10–14-year-olds , respectively ; n = 190 and n = 212 for 15–25-year-olds ) . GMTs for HPV-16 and HPV-18 were higher in 10–14-year-olds ( 18 423 [ 95 % confidence interval , 16 185–20 970 ] and 6487 [ 5590–7529 ] enzyme-linked immunosorbent assay units (EU)/mL , respectively ) than in 15–25-year-olds ( 10 683 [ 9567–11 930 ] and 3743 [ 3400–4120 ] EU/mL , respectively ) . Seropositivity was maintained at month 12 . No participant withdrew owing to adverse events . No vaccine-related serious adverse events were reported . Conclusions . The HPV-16/18 AS04-adjuvanted vaccine was highly immunogenic and had a clinical ly acceptable safety profile when administered to healthy HIV-seronegative African girls and young women Control of human papillomavirus (HPV)-related cancers by inclusion of HPV vaccination into national vaccination programmes is likely . One open question is replacement of the vaccine types with other high-risk ( hr ) HPV types in the vaccination era . We studied occurrence of HPV types in adolescent females participating in a population -based vaccination trial . A total of 4,808 16- to 17-year-old females from Finl and were enrolled in the 1:1 r and omized phase III ( PATRICIA ) trial of the efficacy of vaccination with the  AS04-adjuvanted HPV-16/18 virus-like particle vaccine as compared to hepatitis A virus ( HAV ) vaccine .  HPV infection was assessed from cervical sample s taken every 6 months for 4 years post-vaccination by polymerase chain reaction ( PCR ) for genital oncogenic HPV types 16 , 18 , 31 , 33 , 35 , 39 , 45 , 51 , 52 , 58 , 59 , 66 , 68 , and 73 as well as low-risk types HPV-6 and HPV-11 . The  HPV-16/18 vaccine coverage ranged between 1 and 22 % by age-cohort and study community . Odds ratios ( ORs ) for infections with different HPV types in baseline PCR negative HPV-16/18 vs. HAV vaccinated women , and Poisson regression derived HPV incidence rate ratios ( IRRs ) in baseline positive vs. negative women were calculated . The OR and IRR estimates for acquisition of any genital HPV types showed no excess risk neither in baseline HPV DNA-negative HPV-16/18-vaccinated women compared to baseline HPV DNA-negative HAV vaccinated women nor in HPV-16/18-vaccinated baseline HPV-16/18-positive women compared to baseline HPV-16/18-negative women . In the HAV-vaccinated , baseline HPV-18-positive women showed an increased risk of acquiring other clade A7 HPV types ( 39 , 45 , 59 , 68 ) ( IRR 1.8 , 95 % confidence interval = 1.01.-3.1 ) . We found no increased occurrence of non-vaccine HPV types suggestive of type-replacement 1 - 4 years post- 
    Output:
    