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 . 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 BACKGROUND The investigational 9-valent viruslike particle vaccine against human papillomavirus ( HPV ) includes the HPV types in the quadrivalent HPV ( qHPV ) vaccine ( 6 , 11 , 16 , and 18 ) and five additional oncogenic types ( 31 , 33 , 45 , 52 , and 58 ) . Here we present the results of a study of the efficacy and immunogenicity of the 9vHPV vaccine in women 16 to 26 years of age . METHODS We performed a r and omized , international , double-blind , phase 2b-3 study of the 9vHPV vaccine  in 14,215 women . Participants received the 9vHPV vaccine or the qHPV vaccine in a series of three intramuscular injections on day 1 and at months 2 and 6 . Serum was collected for analysis of antibody responses . Swabs of labial , vulvar , perineal , perianal , endocervical , and ectocervical tissue were obtained and used for HPV DNA testing , and liquid-based cytologic testing ( Papanicolaou testing ) was performed regularly . Tissue obtained by means of biopsy or as part of definitive therapy ( including a loop electrosurgical excision procedure and conization ) was tested for HPV . RESULTS The rate of high- grade cervical , vulvar , or vaginal disease irrespective of HPV type ( i.e. , disease caused by HPV types included in the 9vHPV vaccine and those not included ) in the modified intention-to-treat population ( which included participants with and those without prevalent infection or disease ) was 14.0 per 1000 person-years in both vaccine groups . The rate of high- grade cervical , vulvar , or vaginal disease related to HPV-31 , 33 , 45 , 52 , and 58 in a prespecified per- protocol efficacy population ( susceptible population ) was 0.1 per 1000 person-years in the 9vHPV group and 1.6 per 1000 person-years in the qHPV group ( efficacy of the 9vHPV vaccine , 96.7 % ; 95 % confidence interval , 80.9 to 99.8 ) . Antibody responses to HPV-6 , 11 , 16 , and 18 were noninferior to those generated by the qHPV vaccine . Adverse events related to injection site were more common in the 9vHPV group than in the qHPV group . CONCLUSIONS The 9vHPV vaccine prevented infection and disease related to HPV-31 , 33 , 45 , 52 , and 58 in a susceptible population and generated an antibody response to HPV-6 , 11 , 16 , and 18 that was noninferior to that generated by the qHPV vaccine . The 9vHPV vaccine did not prevent infection and disease related to HPV types beyond the nine types covered by the vaccine . ( Funded by Merck ; Clinical Trials.gov number , NCT00543543 ) IMPORTANCE Global use of human papillomavirus ( HPV ) vaccines to prevent cervical cancer is impeded by cost . A 2-dose schedule for girls may be possible . OBJECTIVE To determine whether mean antibody levels to HPV-16 and HPV-18 among girls receiving 2 doses was noninferior to women receiving 3 doses . DESIGN , SETTING , AND PATIENTS R and omized , phase 3 , postlicensure , multicenter , age-stratified , noninferiority immunogenicity study of 830 Canadian females from August 2007 through February 2011 . Follow-up blood sample s were provided by 675 participants ( 81 % ) . INTERVENTION Girls ( 9 - 13 years ) were r and omized 1:1 to receive 3 doses of quadrivalent HPV vaccine at 0 , 2 , and 6 months ( n = 261 ) or 2 doses at 0 and 6 months ( n = 259 ) . Young women ( 16 - 26 years ) received 3 doses at 0 , 2 , and 6 months ( n = 310 ) . Antibody levels were measured at 0 , 7 , 18 , 24 , and 36 months . MAIN OUTCOMES AND MEASURES Primary outcome was noninferiority ( 95 % CI , lower bound > 0.5 ) of geometric mean titer ( GMT ) ratios for HPV-16 and HPV-18 for girls ( 2 doses ) compared with young women ( 3 doses ) 1 month after last dose . Secondary outcomes were noninferiority of GMT ratios of girls receiving 2 vs 3 doses of vaccine ; and durability of noninferiority to 36 months . RESULTS The GMT ratios were noninferior for girls ( 2 doses ) to women ( 3 doses ) : 2.07 ( 95 % CI , 1.62 - 2.65 ) for HPV-16 and 1.76 ( 95 % CI , 1.41 - 2.19 ) for HPV-18 . Girls ( 3 doses ) had GMT responses 1 month after last vaccination for HPV-16 of 7736 milli-Merck units per mL ( mMU/mL ) ( 95 % CI , 6651 - 8999 ) and HPV-18 of 1730 mMU/mL ( 95 % CI , 1512 - 1980 ) . The GMT ratios were noninferior for girls ( 2 doses ) to girls ( 3 doses ) : 0.95 ( 95 % CI , 0.73 - 1.23 ) for HPV-16 and 0.68 ( 95 % CI , 0.54 - 0.85 ) for HPV-18 . The GMT ratios for girls ( 2 doses ) to women ( 3 doses ) remained noninferior for all genotypes to 36 months . Antibody responses in girls were noninferior after 2 doses vs 3 doses for all 4 vaccine genotypes at month 7 , but not for HPV-18 by month 24 or HPV-6 by month 36 . CONCLUSIONS AND RELEVANCE Among girls who received 2 doses of HPV vaccine 6 months apart , responses to HPV-16 and HPV-18 one month after the last dose were noninferior to those among young women who received 3 doses of the vaccine within 6 months . Because of the loss of noninferiority to some genotypes at 24 to 36 months in girls given 2 doses vs 3 doses , more data on the duration of protection are needed before reduced-dose schedules can be recommended . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00501137 The observer-blind , r and omized , age-stratified , head-to-head study ( NCT00423046 ) comparing immunogenicity and safety of HPV-16/18 and HPV-6/11/16/18 vaccines in healthy women aged 18 - 45 y was completed . Five y after vaccination , in subjects from the Month 60 according-to- protocol cohort ( seronegative and DNA negative for HPV type analyzed at baseline ) , serum neutralizing antibody ( nAb ) responses induced by HPV-16/18 vaccine remained 7.8-fold ( 18 - 26-y stratum ) , 5.6-fold ( 27 - 35-y stratum ) and 2.3-fold ( 36 - 45-y stratum ) higher than those induced by HPV-6/11/16/18 vaccine for HPV-16 . For HPV-18 , the fold differences were 12.1 , 13.0 and 7.8 , respectively . At Month 60 , all ( 100 % ) subjects in HPV-16/18 vaccine group and the majority ( 95.7%-97.5 % ) in HPV-6/11/16/18 vaccine group were seropositive for HPV-16 . For HPV-18 , the majority ( 98.1%-100 % ) of subjects in HPV-16/18 vaccine group were seropositive ; however , seropositivity rates in HPV-6/11/16/18 vaccine group decreased considerably ( 61.1%-76.9 % ) across the 3 age strata . In the total vaccinated cohort ( received ≥ 1 dose regardless of baseline HPV serostatus and DNA status ) , geometric mean titers for anti-HPV-16 and anti-HPV-18 nAb were higher in HPV-16/18 vaccine group than in HPV-6/11/16/18 vaccine group . Based on the 5-y data , piece-wise and modified power-law models predicted a longer durability of nAb response for HPV-16/18 vaccine compared to HPV-6/11/16/18 vaccine . Beyond the differences apparent between the vaccines in terms of immunogenicity and modeled persistence of antibody responses , comparative studies including clinical endpoints would be needed to determine whether differences exist in duration of vaccine-induced protection The Costa Rica HPV16/18 Vaccine Trial ( CVT ) showed that four-year vaccine efficacy against 12-month HPV16/18 persistent infection was similarly high among women who received one , two , or the recommended three doses of the bivalent HPV16/18 L1 virus-like particle ( VLP ) vaccine . Live-attenuated viral vaccines , but not simple-subunit vaccines , usually induce durable lifelong antibody responses after a single dose . It is unclear whether noninfectious VLP vaccines behave more like live-virus or simple-subunit vaccines in this regard . To explore the likelihood that efficacy will persist longer term , we investigated the magnitude and durability of antibodies to this vaccine by measuring HPV16- and HPV18-specific antibodies by VLP-ELISA using serum from enrollment , vaccination , and annual visits through four years in four vaccinated groups ; one-dose ( n = 78 ) , two-doses separated by one month ( n = 140 ) ,  two doses separated by six months ( n = 52 ) , and three scheduled doses ( n = 120 , r and omly selected ) . We also tested enrollment sera from n = 113 HPV16- or HPV18 L1-seropositive women prevaccination , presumably from natural infection . At four years , 100 % of women in all groups remained HPV16/18 seropositive ; both 
    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 . 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 BACKGROUND The investigational 9-valent viruslike particle vaccine against human papillomavirus ( HPV ) includes the HPV types in the quadrivalent HPV ( qHPV ) vaccine ( 6 , 11 , 16 , and 18 ) and five additional oncogenic types ( 31 , 33 , 45 , 52 , and 58 ) . Here we present the results of a study of the efficacy and immunogenicity of the 9vHPV vaccine in women 16 to 26 years of age . METHODS We performed a r and omized , international , double-blind , phase 2b-3 study of the 9vHPV vaccine  in 14,215 women . Participants received the 9vHPV vaccine or the qHPV vaccine in a series of three intramuscular injections on day 1 and at months 2 and 6 . Serum was collected for analysis of antibody responses . Swabs of labial , vulvar , perineal , perianal , endocervical , and ectocervical tissue were obtained and used for HPV DNA testing , and liquid-based cytologic testing ( Papanicolaou testing ) was performed regularly . Tissue obtained by means of biopsy or as part of definitive therapy ( including a loop electrosurgical excision procedure and conization ) was tested for HPV . RESULTS The rate of high- grade cervical , vulvar , or vaginal disease irrespective of HPV type ( i.e. , disease caused by HPV types included in the 9vHPV vaccine and those not included ) in the modified intention-to-treat population ( which included participants with and those without prevalent infection or disease ) was 14.0 per 1000 person-years in both vaccine groups . The rate of high- grade cervical , vulvar , or vaginal disease related to HPV-31 , 33 , 45 , 52 , and 58 in a prespecified per- protocol efficacy population ( susceptible population ) was 0.1 per 1000 person-years in the 9vHPV group and 1.6 per 1000 person-years in the qHPV group ( efficacy of the 9vHPV vaccine , 96.7 % ; 95 % confidence interval , 80.9 to 99.8 ) . Antibody responses to HPV-6 , 11 , 16 , and 18 were noninferior to those generated by the qHPV vaccine . Adverse events related to injection site were more common in the 9vHPV group than in the qHPV group . CONCLUSIONS The 9vHPV vaccine prevented infection and disease related to HPV-31 , 33 , 45 , 52 , and 58 in a susceptible population and generated an antibody response to HPV-6 , 11 , 16 , and 18 that was noninferior to that generated by the qHPV vaccine . The 9vHPV vaccine did not prevent infection and disease related to HPV types beyond the nine types covered by the vaccine . ( Funded by Merck ; Clinical Trials.gov number , NCT00543543 ) IMPORTANCE Global use of human papillomavirus ( HPV ) vaccines to prevent cervical cancer is impeded by cost . A 2-dose schedule for girls may be possible . OBJECTIVE To determine whether mean antibody levels to HPV-16 and HPV-18 among girls receiving 2 doses was noninferior to women receiving 3 doses . DESIGN , SETTING , AND PATIENTS R and omized , phase 3 , postlicensure , multicenter , age-stratified , noninferiority immunogenicity study of 830 Canadian females from August 2007 through February 2011 . Follow-up blood sample s were provided by 675 participants ( 81 % ) . INTERVENTION Girls ( 9 - 13 years ) were r and omized 1:1 to receive 3 doses of quadrivalent HPV vaccine at 0 , 2 , and 6 months ( n = 261 ) or 2 doses at 0 and 6 months ( n = 259 ) . Young women ( 16 - 26 years ) received 3 doses at 0 , 2 , and 6 months ( n = 310 ) . Antibody levels were measured at 0 , 7 , 18 , 24 , and 36 months . MAIN OUTCOMES AND MEASURES Primary outcome was noninferiority ( 95 % CI , lower bound > 0.5 ) of geometric mean titer ( GMT ) ratios for HPV-16 and HPV-18 for girls ( 2 doses ) compared with young women ( 3 doses ) 1 month after last dose . Secondary outcomes were noninferiority of GMT ratios of girls receiving 2 vs 3 doses of vaccine ; and durability of noninferiority to 36 months . RESULTS The GMT ratios were noninferior for girls ( 2 doses ) to women ( 3 doses ) : 2.07 ( 95 % CI , 1.62 - 2.65 ) for HPV-16 and 1.76 ( 95 % CI , 1.41 - 2.19 ) for HPV-18 . Girls ( 3 doses ) had GMT responses 1 month after last vaccination for HPV-16 of 7736 milli-Merck units per mL ( mMU/mL ) ( 95 % CI , 6651 - 8999 ) and HPV-18 of 1730 mMU/mL ( 95 % CI , 1512 - 1980 ) . The GMT ratios were noninferior for girls ( 2 doses ) to girls ( 3 doses ) : 0.95 ( 95 % CI , 0.73 - 1.23 ) for HPV-16 and 0.68 ( 95 % CI , 0.54 - 0.85 ) for HPV-18 . The GMT ratios for girls ( 2 doses ) to women ( 3 doses ) remained noninferior for all genotypes to 36 months . Antibody responses in girls were noninferior after 2 doses vs 3 doses for all 4 vaccine genotypes at month 7 , but not for HPV-18 by month 24 or HPV-6 by month 36 . CONCLUSIONS AND RELEVANCE Among girls who received 2 doses of HPV vaccine 6 months apart , responses to HPV-16 and HPV-18 one month after the last dose were noninferior to those among young women who received 3 doses of the vaccine within 6 months . Because of the loss of noninferiority to some genotypes at 24 to 36 months in girls given 2 doses vs 3 doses , more data on the duration of protection are needed before reduced-dose schedules can be recommended . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00501137 The observer-blind , r and omized , age-stratified , head-to-head study ( NCT00423046 ) comparing immunogenicity and safety of HPV-16/18 and HPV-6/11/16/18 vaccines in healthy women aged 18 - 45 y was completed . Five y after vaccination , in subjects from the Month 60 according-to- protocol cohort ( seronegative and DNA negative for HPV type analyzed at baseline ) , serum neutralizing antibody ( nAb ) responses induced by HPV-16/18 vaccine remained 7.8-fold ( 18 - 26-y stratum ) , 5.6-fold ( 27 - 35-y stratum ) and 2.3-fold ( 36 - 45-y stratum ) higher than those induced by HPV-6/11/16/18 vaccine for HPV-16 . For HPV-18 , the fold differences were 12.1 , 13.0 and 7.8 , respectively . At Month 60 , all ( 100 % ) subjects in HPV-16/18 vaccine group and the majority ( 95.7%-97.5 % ) in HPV-6/11/16/18 vaccine group were seropositive for HPV-16 . For HPV-18 , the majority ( 98.1%-100 % ) of subjects in HPV-16/18 vaccine group were seropositive ; however , seropositivity rates in HPV-6/11/16/18 vaccine group decreased considerably ( 61.1%-76.9 % ) across the 3 age strata . In the total vaccinated cohort ( received ≥ 1 dose regardless of baseline HPV serostatus and DNA status ) , geometric mean titers for anti-HPV-16 and anti-HPV-18 nAb were higher in HPV-16/18 vaccine group than in HPV-6/11/16/18 vaccine group . Based on the 5-y data , piece-wise and modified power-law models predicted a longer durability of nAb response for HPV-16/18 vaccine compared to HPV-6/11/16/18 vaccine . Beyond the differences apparent between the vaccines in terms of immunogenicity and modeled persistence of antibody responses , comparative studies including clinical endpoints would be needed to determine whether differences exist in duration of vaccine-induced protection The Costa Rica HPV16/18 Vaccine Trial ( CVT ) showed that four-year vaccine efficacy against 12-month HPV16/18 persistent infection was similarly high among women who received one , two , or the recommended three doses of the bivalent HPV16/18 L1 virus-like particle ( VLP ) vaccine . Live-attenuated viral vaccines , but not simple-subunit vaccines , usually induce durable lifelong antibody responses after a single dose . It is unclear whether noninfectious VLP vaccines behave more like live-virus or simple-subunit vaccines in this regard . To explore the likelihood that efficacy will persist longer term , we investigated the magnitude and durability of antibodies to this vaccine by measuring HPV16- and HPV18-specific antibodies by VLP-ELISA using serum from enrollment , vaccination , and annual visits through four years in four vaccinated groups ; one-dose ( n = 78 ) , two-doses separated by one month ( n = 140 ) ,  two doses separated by six months ( n = 52 ) , and three scheduled doses ( n = 120 , r and omly selected ) . We also tested enrollment sera from n = 113 HPV16- or HPV18 L1-seropositive women prevaccination , presumably from natural infection . At four years , 100 % of women in all groups remained HPV16/18 seropositive ; both 
    Output:
    