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: PURPOSE The human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine ( Cervarix ) has been shown to be well-tolerated and immunogenic in females aged 10 to 55 years , and up to 100 % effective for the prevention of HPV-16/18 infection and associated precancerous cervical lesions in females aged 15 to 25 years . This study is the first to evaluate the immunogenicity and safety of the vaccine in males . METHODS Healthy males aged 10 to 18 years were r and omized ( 2:1 ratio ) to receive  HPV-16/18 AS04-adjuvanted vaccine ( n = 181 ) or hepatitis B virus ( HBV ) control vaccine ( n = 89 ) at 0 , 1 , and 6 months , and were followed for 7 months . RESULTS All initially seronegative subjects in the HPV-16/18 group seroconverted for HPV-16 and 18 ( ELISA ) at month 2 . At month 7 , all subjects were seropositive , and the HPV-16 and -18 antibody levels were , respectively , four- and twofold higher than at month 2 . The anti-HPV-16 and -18 antibody responses for males aged 10 to 18 years and 10 to 14 years , respectively , were higher than those reported for females aged 15 to 25 years and 10 to 14 years , respectively , in a previous study . The reactogenicity profiles of the HPV-16/18 AS04 and HBV vaccines were similar , except that pain and swelling at the injection site were more common in the HPV-16/18 group . However , vaccine-related symptoms did not affect compliance with the three-dose course , which was equally high ( 97 % ) in both groups . CONCLUSIONS The HPV-16/18 AS04-adjuvanted vaccine is immunogenic and well tolerated in boys aged 10 to 18 years . However , further data on the potential public health benefits of vaccination of boys are required before any recommendations can be made 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 In this r and omized , double-blind , placebo-controlled trial , 9 - 15 year old Chinese males ( n=100 ) and 9 - 45 year old Chinese females ( n=500 ) from Wuzhou , Guangxi , China were r and omized ( 1:1 ) to receive either quadrivalent HPV vaccine or adjuvant-containing placebo .  Blood sample s were obtained at day 1 and one month post-dose 3 to determine the level of vaccine-induced antibodies . Among vaccine recipients , high antibody levels were observed for each of the four HPV types and seroconversion was > 96 % . The vaccine was generally well tolerated , with no vaccine-related serious adverse events . This study demonstrated that the quadrivalent HPV vaccine is highly immunogenic and generally well tolerated among Chinese males and females 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 ] . ) The human papillomavirus (HPV)-16/18 AS04-adjuvanted cervical cancer vaccine has been demonstrated to be highly efficacious and immunogenic with a favorable safety profile . This study assessed the immunogenicity and safety of the HPV-16/18 AS04-adjuvanted vaccine in healthy Korean girls aged 10 - 14 yr . This multi-center , observer-blind trial r and omly assigned 321 healthy girls to receive three doses ( 0 , 1 , 6-month schedule ) of HPV-16/18 AS04-adjuvanted vaccine or hepatitis A vaccine . Immunogenicity against vaccine antigens was assessed one month post-Dose 3 . Solicited and unsolicited adverse events ( AEs ) and serious AEs ( SAEs ) were recorded . In the according-to- protocol analysis , all initially seronegative subjects vaccinated with the HPV-16/18 AS04-adjuvanted vaccine had seroconverted at Month 7 , with a peak geometric mean titer ( GMT ) that was 600-fold higher than the natural infection titer of 29.8 EU/mL for HPV-16 and a peak GMT that was 400-fold higher than the natural infection titer of 22.6 EU/mL for HPV-18 . The vaccine was well tolerated with no increase in reactogenicity with subsequent doses and no reports of vaccine-related SAEs . In conclusion , the HPV-16/18 AS04-adjuvanted vaccine is shown to be highly immunogenic and generally well-tolerated in Korean girls aged 10 - 14 yr BACKGROUND Human papillomavirus types 16 ( HPV-16 ) and 18 ( HPV-18 ) cause approximately 70 % of cervical cancers worldwide . A phase 3 trial was conducted to evaluate a quadrivalent vaccine against HPV types 6 , 11 , 16 , and 18 ( HPV-6/11/16/18 ) for the prevention of high- grade cervical lesions associated with HPV-16 and HPV-18 . METHODS In this r and omized , double-blind trial , we assigned 12,167 women between the ages of 15 and 26 years to receive three doses of either HPV-6/11/16/18 vaccine or placebo , administered at day 1 , month 2 , and month 6 . The primary analysis was performed for a per- protocol susceptible population that included 5305 women in the vaccine group and 5260 in the placebo group who had no virologic evidence of infection with HPV-16 or HPV-18 through 1 month after the third dose ( month 7 ) . The primary composite end point was cervical intraepithelial neoplasia grade 2 or 3 , adenocarcinoma in situ , or cervical cancer related to HPV-16 or HPV-18 . RESULTS Subjects were followed for an average of 3 years after receiving the first dose of vaccine or placebo .  Vaccine efficacy for the prevention of the primary composite end point was 98 % ( 95.89 % confidence interval [ CI ] , 86 to 100 ) in the per- protocol susceptible population and 44 % ( 95 % CI , 26 to 58 ) in an intention-to-treat population of all women who had undergone r and omization ( those with or without previous infection ) . The estimated vaccine efficacy against all high- grade cervical lesions , regardless of causal HPV type , in this intention-to-treat population was 17 % ( 95 % CI , 1 to 31 ) . CONCLUSIONS In young women who had not been previously infected with HPV-16 or HPV-18 , those in the vaccine group had a significantly lower occurrence of high- grade cervical intraepithelial neoplasia related to HPV-16 or HPV-18 than did those in the placebo group . ( Clinical Trials.gov number , NCT00092534 [ Clinical Trials.gov ] . ) In the Phase III PATRICIA study ( NCT00122681 ) , the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine ( Cervarix ( ® ) , GlaxoSmithKline Biologicals ) was highly efficacious against HPV-16/18 infections and precancerous lesions in women HPV-16/18 deoxyribose nucleic acid ( DNA ) negative and seronegative at baseline . We present further data on vaccine efficacy ( VE ) against HPV-16/18 in the total vaccinated cohort including women who may have been exposed to HPV-16/18 infection before vaccination . In women with no evidence of current or previous HPV-16/18 infection ( DNA negative and seronegative ) , VE was 90.3 % ( 96.1 % confidence interval : 87.3 - 92.6 ) against 6-month persistent infection ( PI ) , 91.9 % ( 84.6 - 96.2 ) against cervical intraepithelial neoplasia (CIN)1 + and 94.6 % ( 86.3 - 98.4 ) against CIN2 + [ 97.7 % ( 91.1 - 99.8 ) when using the HPV type assignment algorithm ( TAA ) ] . In women HPV-16/18 DNA negative but with serological evidence of previous HPV 
    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: PURPOSE The human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine ( Cervarix ) has been shown to be well-tolerated and immunogenic in females aged 10 to 55 years , and up to 100 % effective for the prevention of HPV-16/18 infection and associated precancerous cervical lesions in females aged 15 to 25 years . This study is the first to evaluate the immunogenicity and safety of the vaccine in males . METHODS Healthy males aged 10 to 18 years were r and omized ( 2:1 ratio ) to receive  HPV-16/18 AS04-adjuvanted vaccine ( n = 181 ) or hepatitis B virus ( HBV ) control vaccine ( n = 89 ) at 0 , 1 , and 6 months , and were followed for 7 months . RESULTS All initially seronegative subjects in the HPV-16/18 group seroconverted for HPV-16 and 18 ( ELISA ) at month 2 . At month 7 , all subjects were seropositive , and the HPV-16 and -18 antibody levels were , respectively , four- and twofold higher than at month 2 . The anti-HPV-16 and -18 antibody responses for males aged 10 to 18 years and 10 to 14 years , respectively , were higher than those reported for females aged 15 to 25 years and 10 to 14 years , respectively , in a previous study . The reactogenicity profiles of the HPV-16/18 AS04 and HBV vaccines were similar , except that pain and swelling at the injection site were more common in the HPV-16/18 group . However , vaccine-related symptoms did not affect compliance with the three-dose course , which was equally high ( 97 % ) in both groups . CONCLUSIONS The HPV-16/18 AS04-adjuvanted vaccine is immunogenic and well tolerated in boys aged 10 to 18 years . However , further data on the potential public health benefits of vaccination of boys are required before any recommendations can be made 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 In this r and omized , double-blind , placebo-controlled trial , 9 - 15 year old Chinese males ( n=100 ) and 9 - 45 year old Chinese females ( n=500 ) from Wuzhou , Guangxi , China were r and omized ( 1:1 ) to receive either quadrivalent HPV vaccine or adjuvant-containing placebo .  Blood sample s were obtained at day 1 and one month post-dose 3 to determine the level of vaccine-induced antibodies . Among vaccine recipients , high antibody levels were observed for each of the four HPV types and seroconversion was > 96 % . The vaccine was generally well tolerated , with no vaccine-related serious adverse events . This study demonstrated that the quadrivalent HPV vaccine is highly immunogenic and generally well tolerated among Chinese males and females 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 ] . ) The human papillomavirus (HPV)-16/18 AS04-adjuvanted cervical cancer vaccine has been demonstrated to be highly efficacious and immunogenic with a favorable safety profile . This study assessed the immunogenicity and safety of the HPV-16/18 AS04-adjuvanted vaccine in healthy Korean girls aged 10 - 14 yr . This multi-center , observer-blind trial r and omly assigned 321 healthy girls to receive three doses ( 0 , 1 , 6-month schedule ) of HPV-16/18 AS04-adjuvanted vaccine or hepatitis A vaccine . Immunogenicity against vaccine antigens was assessed one month post-Dose 3 . Solicited and unsolicited adverse events ( AEs ) and serious AEs ( SAEs ) were recorded . In the according-to- protocol analysis , all initially seronegative subjects vaccinated with the HPV-16/18 AS04-adjuvanted vaccine had seroconverted at Month 7 , with a peak geometric mean titer ( GMT ) that was 600-fold higher than the natural infection titer of 29.8 EU/mL for HPV-16 and a peak GMT that was 400-fold higher than the natural infection titer of 22.6 EU/mL for HPV-18 . The vaccine was well tolerated with no increase in reactogenicity with subsequent doses and no reports of vaccine-related SAEs . In conclusion , the HPV-16/18 AS04-adjuvanted vaccine is shown to be highly immunogenic and generally well-tolerated in Korean girls aged 10 - 14 yr BACKGROUND Human papillomavirus types 16 ( HPV-16 ) and 18 ( HPV-18 ) cause approximately 70 % of cervical cancers worldwide . A phase 3 trial was conducted to evaluate a quadrivalent vaccine against HPV types 6 , 11 , 16 , and 18 ( HPV-6/11/16/18 ) for the prevention of high- grade cervical lesions associated with HPV-16 and HPV-18 . METHODS In this r and omized , double-blind trial , we assigned 12,167 women between the ages of 15 and 26 years to receive three doses of either HPV-6/11/16/18 vaccine or placebo , administered at day 1 , month 2 , and month 6 . The primary analysis was performed for a per- protocol susceptible population that included 5305 women in the vaccine group and 5260 in the placebo group who had no virologic evidence of infection with HPV-16 or HPV-18 through 1 month after the third dose ( month 7 ) . The primary composite end point was cervical intraepithelial neoplasia grade 2 or 3 , adenocarcinoma in situ , or cervical cancer related to HPV-16 or HPV-18 . RESULTS Subjects were followed for an average of 3 years after receiving the first dose of vaccine or placebo .  Vaccine efficacy for the prevention of the primary composite end point was 98 % ( 95.89 % confidence interval [ CI ] , 86 to 100 ) in the per- protocol susceptible population and 44 % ( 95 % CI , 26 to 58 ) in an intention-to-treat population of all women who had undergone r and omization ( those with or without previous infection ) . The estimated vaccine efficacy against all high- grade cervical lesions , regardless of causal HPV type , in this intention-to-treat population was 17 % ( 95 % CI , 1 to 31 ) . CONCLUSIONS In young women who had not been previously infected with HPV-16 or HPV-18 , those in the vaccine group had a significantly lower occurrence of high- grade cervical intraepithelial neoplasia related to HPV-16 or HPV-18 than did those in the placebo group . ( Clinical Trials.gov number , NCT00092534 [ Clinical Trials.gov ] . ) In the Phase III PATRICIA study ( NCT00122681 ) , the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine ( Cervarix ( ® ) , GlaxoSmithKline Biologicals ) was highly efficacious against HPV-16/18 infections and precancerous lesions in women HPV-16/18 deoxyribose nucleic acid ( DNA ) negative and seronegative at baseline . We present further data on vaccine efficacy ( VE ) against HPV-16/18 in the total vaccinated cohort including women who may have been exposed to HPV-16/18 infection before vaccination . In women with no evidence of current or previous HPV-16/18 infection ( DNA negative and seronegative ) , VE was 90.3 % ( 96.1 % confidence interval : 87.3 - 92.6 ) against 6-month persistent infection ( PI ) , 91.9 % ( 84.6 - 96.2 ) against cervical intraepithelial neoplasia (CIN)1 + and 94.6 % ( 86.3 - 98.4 ) against CIN2 + [ 97.7 % ( 91.1 - 99.8 ) when using the HPV type assignment algorithm ( TAA ) ] . In women HPV-16/18 DNA negative but with serological evidence of previous HPV 
    Output:
    