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 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 ] . ) BACKGROUND Effective vaccination against HPV 16 and HPV 18 to prevent cervical cancer will require a high level of sustained protection against infection and precancerous lesions . Our aim was to assess the long-term efficacy , immunogenicity , and safety of a bivalent HPV-16/18 L1 virus-like particle AS04 vaccine against incident and persistent infection with HPV 16 and HPV 18 and their associated cytological and histological outcomes . METHODS We did a follow-up study of our multicentre , double-blind , r and omised , placebo-controlled trial reported in 2004 . We included women who originally received all three doses of bivalent HPV-16/18 virus-like particle AS04 vaccine ( 0.5 mL ; n=393 ) or placebo ( n=383 ) . We assessed HPV DNA , using cervical sample s , and did yearly cervical cytology assessment s. We also studied the long-term immunogenicity and safety of the vaccine . FINDINGS More than 98 % seropositivity was maintained for HPV-16/18 antibodies during the extended follow-up phase . We noted significant vaccine efficacy against HPV-16 and HPV-18 endpoints : incident infection , 96.9 % ( 95 % CI 81.3 - 99.9 ) ; persistent infection : 6 month definition , 94.3 ( 63.2 - 99.9 ) ; 12 month definition , 100 % ( 33.6 - 100 ) . In a combined analysis of the initial efficacy and extended follow-up studies , vaccine efficacy of 100 % ( 42.4 - 100 ) against cervical intraepithelial neoplasia ( CIN ) lesions associated with vaccine types . We noted broad protection against cytohistological outcomes beyond that anticipated for HPV 16/18 and protection against incident infection with HPV 45 and HPV 31 . The vaccine has a good long-term safety profile . INTERPRETATION Up to 4.5 years , the HPV-16/18 L1 virus-like particle AS04 vaccine is highly immunogenic and safe , and induces a high degree of protection against HPV-16/18 infection and associated cervical lesions . There is also evidence of cross protection BACKGROUND We evaluated the impact of a quadrivalent human papillomavirus ( HPV ) vaccine on infection and cervical disease related to 10 nonvaccine HPV types ( 31 , 33 , 35 , 39 , 45 , 51 , 52 , 56 , 58 , and 59 ) associated with > 20 % of cervical cancers . The population evaluated included HPV-naive women and women with preexisting HPV infection and /or HPV-related disease at enrollment . METHODS Phase 3 efficacy studies enrolled 17,622 women aged 16 - 26 years . Subjects underwent cervicovaginal sampling and Pap testing on day 1 and then at 6 - 12-month intervals for up to 4 years . HPV typing was performed on sample s from enrollment and follow-up visits , including sample s obtained for diagnosis or treatment of HPV-related disease . All subjects who received 1 dose and returned for follow-up were included . RESULTS Vaccination reduced the rate of HPV-31/33/45/52/58 infection by 17.7 % ( 95 % confidence interval [ CI ] , 5.1 % to 28.7 % ) and of cervical intraepithelial neoplasia ( CIN ) 1 - 3 or adenocarcinoma in situ ( AIS ) by 18.8 % ( 95 % CI , 7.4 % to 28.9 % ) . Vaccination also reduced the rate of HPV-31/58/59-related CIN1 - 3/AIS by 26.0 % ( 95 % CI , 6.7 % to 41.4 % ) , 28.1 % ( 95 % CI , 5.3 % to 45.6 % ) , and 37.6 % ( 95 % CI , 6.0 % to 59.1 % ) , respectively . Although a modest reduction in HPV-31/33/45/52/58-related CIN2 or worse was observed , the estimated reduction was not statistically significant . CONCLUSIONS These cross-protection results complement the vaccine 's prophylactic efficacy against disease associated with HPV-6 , -11 , -16 , and -18 . Long-term monitoring of vaccinated population s are needed to fully ascertain the population -based impact and public health significance of these findings . TRIAL REGISTRATION Clinical Trials.gov identifiers : NCT00092521 , NCT00092534 , and NCT00092482 Protection against oncogenic non-vaccine types ( cross-protection ) offered by human papillomavirus ( HPV ) vaccines may provide a significant medical benefit . Available clinical efficacy data suggest the two licensed vaccines ( HPV-16/18 vaccine , GlaxoSmithKline Biologicals [ GSK ] , and HPV-6/11/16/18 vaccine , Merck & Co. , Inc. ) differ in terms of protection against oncogenic non-vaccine HPV types -31/45 . The immune responses induced by the two vaccines against these two non-vaccine HPV types ( cross-reactivity ) was compared in an observer-blind study up to Month 24 ( 18 months post-vaccination ) , in women HPV DNA-negative and seronegative prior to vaccination for the HPV type analyzed ( HPV-010 [ NCT00423046 ] ) . Geometric mean antibody titers ( GMTs ) measured by pseudovirion-based neutralization assay ( PBNA ) and enzyme-linked immunosorbent assay ( ELISA ) were similar between vaccines for HPV-31/45 . Seropositivity rates for HPV-31 were also similar between vaccines ; however , there was a trend for higher seropositivity with the HPV-16/18 vaccine ( 13.0–16.7 % ) versus the HPV-6/11/16/18 vaccine ( 0.0–5.0 % ) for HPV-45 with PBNA , but not ELISA . HPV-31/45 cross-reactive memory B-cell responses were comparable between vaccines . Circulating antigen-specific CD4 + T-cell frequencies were higher for the HPV-16/18 vaccine than the HPV-6/11/16/18 vaccine ( HPV-31 [ geometric mean ratio [ GMR ] = 2.0 ; p=0.0002 ] and HPV-45 [ GMR=2.6 ; p=0.0092 ] ) , as were the proportion of T-cell responders ( HPV-31 , p=0.0009 ; HPV-45 , p=0.0793 ) . In conclusion , immune response to oncogenic non-vaccine HPV types -31/45 was generally similar for both vaccines with the exception of T-cell response which was higher with the HPV-16/18 vaccine . Considering the differences in cross-protective efficacy between the two vaccines , the results might provide insights into the underlying mechanism( 
    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 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 ] . ) BACKGROUND Effective vaccination against HPV 16 and HPV 18 to prevent cervical cancer will require a high level of sustained protection against infection and precancerous lesions . Our aim was to assess the long-term efficacy , immunogenicity , and safety of a bivalent HPV-16/18 L1 virus-like particle AS04 vaccine against incident and persistent infection with HPV 16 and HPV 18 and their associated cytological and histological outcomes . METHODS We did a follow-up study of our multicentre , double-blind , r and omised , placebo-controlled trial reported in 2004 . We included women who originally received all three doses of bivalent HPV-16/18 virus-like particle AS04 vaccine ( 0.5 mL ; n=393 ) or placebo ( n=383 ) . We assessed HPV DNA , using cervical sample s , and did yearly cervical cytology assessment s. We also studied the long-term immunogenicity and safety of the vaccine . FINDINGS More than 98 % seropositivity was maintained for HPV-16/18 antibodies during the extended follow-up phase . We noted significant vaccine efficacy against HPV-16 and HPV-18 endpoints : incident infection , 96.9 % ( 95 % CI 81.3 - 99.9 ) ; persistent infection : 6 month definition , 94.3 ( 63.2 - 99.9 ) ; 12 month definition , 100 % ( 33.6 - 100 ) . In a combined analysis of the initial efficacy and extended follow-up studies , vaccine efficacy of 100 % ( 42.4 - 100 ) against cervical intraepithelial neoplasia ( CIN ) lesions associated with vaccine types . We noted broad protection against cytohistological outcomes beyond that anticipated for HPV 16/18 and protection against incident infection with HPV 45 and HPV 31 . The vaccine has a good long-term safety profile . INTERPRETATION Up to 4.5 years , the HPV-16/18 L1 virus-like particle AS04 vaccine is highly immunogenic and safe , and induces a high degree of protection against HPV-16/18 infection and associated cervical lesions . There is also evidence of cross protection BACKGROUND We evaluated the impact of a quadrivalent human papillomavirus ( HPV ) vaccine on infection and cervical disease related to 10 nonvaccine HPV types ( 31 , 33 , 35 , 39 , 45 , 51 , 52 , 56 , 58 , and 59 ) associated with > 20 % of cervical cancers . The population evaluated included HPV-naive women and women with preexisting HPV infection and /or HPV-related disease at enrollment . METHODS Phase 3 efficacy studies enrolled 17,622 women aged 16 - 26 years . Subjects underwent cervicovaginal sampling and Pap testing on day 1 and then at 6 - 12-month intervals for up to 4 years . HPV typing was performed on sample s from enrollment and follow-up visits , including sample s obtained for diagnosis or treatment of HPV-related disease . All subjects who received 1 dose and returned for follow-up were included . RESULTS Vaccination reduced the rate of HPV-31/33/45/52/58 infection by 17.7 % ( 95 % confidence interval [ CI ] , 5.1 % to 28.7 % ) and of cervical intraepithelial neoplasia ( CIN ) 1 - 3 or adenocarcinoma in situ ( AIS ) by 18.8 % ( 95 % CI , 7.4 % to 28.9 % ) . Vaccination also reduced the rate of HPV-31/58/59-related CIN1 - 3/AIS by 26.0 % ( 95 % CI , 6.7 % to 41.4 % ) , 28.1 % ( 95 % CI , 5.3 % to 45.6 % ) , and 37.6 % ( 95 % CI , 6.0 % to 59.1 % ) , respectively . Although a modest reduction in HPV-31/33/45/52/58-related CIN2 or worse was observed , the estimated reduction was not statistically significant . CONCLUSIONS These cross-protection results complement the vaccine 's prophylactic efficacy against disease associated with HPV-6 , -11 , -16 , and -18 . Long-term monitoring of vaccinated population s are needed to fully ascertain the population -based impact and public health significance of these findings . TRIAL REGISTRATION Clinical Trials.gov identifiers : NCT00092521 , NCT00092534 , and NCT00092482 Protection against oncogenic non-vaccine types ( cross-protection ) offered by human papillomavirus ( HPV ) vaccines may provide a significant medical benefit . Available clinical efficacy data suggest the two licensed vaccines ( HPV-16/18 vaccine , GlaxoSmithKline Biologicals [ GSK ] , and HPV-6/11/16/18 vaccine , Merck & Co. , Inc. ) differ in terms of protection against oncogenic non-vaccine HPV types -31/45 . The immune responses induced by the two vaccines against these two non-vaccine HPV types ( cross-reactivity ) was compared in an observer-blind study up to Month 24 ( 18 months post-vaccination ) , in women HPV DNA-negative and seronegative prior to vaccination for the HPV type analyzed ( HPV-010 [ NCT00423046 ] ) . Geometric mean antibody titers ( GMTs ) measured by pseudovirion-based neutralization assay ( PBNA ) and enzyme-linked immunosorbent assay ( ELISA ) were similar between vaccines for HPV-31/45 . Seropositivity rates for HPV-31 were also similar between vaccines ; however , there was a trend for higher seropositivity with the HPV-16/18 vaccine ( 13.0–16.7 % ) versus the HPV-6/11/16/18 vaccine ( 0.0–5.0 % ) for HPV-45 with PBNA , but not ELISA . HPV-31/45 cross-reactive memory B-cell responses were comparable between vaccines . Circulating antigen-specific CD4 + T-cell frequencies were higher for the HPV-16/18 vaccine than the HPV-6/11/16/18 vaccine ( HPV-31 [ geometric mean ratio [ GMR ] = 2.0 ; p=0.0002 ] and HPV-45 [ GMR=2.6 ; p=0.0092 ] ) , as were the proportion of T-cell responders ( HPV-31 , p=0.0009 ; HPV-45 , p=0.0793 ) . In conclusion , immune response to oncogenic non-vaccine HPV types -31/45 was generally similar for both vaccines with the exception of T-cell response which was higher with the HPV-16/18 vaccine . Considering the differences in cross-protective efficacy between the two vaccines , the results might provide insights into the underlying mechanism( 
    Output:
    