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 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 ) AIM India has the highest number of annual incident cases and mortality rates for cervical cancer worldwide . This study was conducted to assess the immunogenicity and safety of human papillomavirus (HPV)-16/18 AS04-adjuvanted cervical cancer vaccine in healthy Indian women aged 18 - 35 years old . METHODS This double-blind , r and omized ( 1:1 ) , controlled and multicenter trial with two parallel groups , the Vaccine and  Placebo groups , included 354 subjects in four centers across India . Subjects were given GlaxoSmithKline 's HPV-16/18 AS04-adjuvanted cervical cancer vaccine or aluminum hydroxide placebo according to a 0 , 1 and 6 month schedule and followed up until month 7 . Serum sample s were drawn at pre-vaccination and at month 7 . Safety data were collected throughout the study . RESULTS A total of 330 subjects completed the study . One month post-Dose 3 , all initially seronegative subjects in the Vaccine group had seroconverted for HPV-16 and HPV-18 antibodies with anti-HPV-16 and anti-HPV-18 geometric mean titer levels of 10226.5 EL.U/ml ( 95 % confidence interval : 8847.1 - 11821.0 ) and 3953.0 EL.U/ml ( 95 % confidence interval : 3421.8 - 4566.8 ) , respectively . Initially seropositive subjects also showed an increase to similar geometric mean titer levels . Six serious adverse events ( two in the Vaccine group and four in the Placebo group ) , all unrelated to vaccination , were reported . Commonly reported solicited local ( injection-site pain ) and general ( fatigue , headache and fever ) symptoms were similar in both groups . Compliance to the three-dose vaccination course was > 97 % . CONCLUSIONS The AS04-adjuvanted HPV-16/18 cervical cancer vaccine was highly immunogenic and generally well-tolerated making it a potential tool for prevention and control of cervical cancer in India OBJECTIVE To assess the immunogenicity and safety of human papillomavirus-16/18 AS04-adjuvanted cervical cancer vaccine in Chinese women aged 18 to 35 years enrolled from Hong Kong . DESIGN Double-blind , r and omised controlled trial with vaccine and placebo groups . SETTING Single-centre study in Hong Kong . PARTICIPANTS Three hundred women enrolled ( 150 per group ) between March 2006 and June 2007 . INTERVENTIONS Subjects received three doses of human papillomavirus-16/18 vaccine or placebo ( aluminium hydroxide ) , administered intramuscularly at 0 , 1 , and 6 months . MAIN OUTCOME MEASURES Human papillomavirus-16/18 seroconversion rates and geometric mean titres at month 7 ( in human papillomavirus-16/18 recipients ) ; reactogenicity and safety ( in all subjects ) . RESULTS A total of 294 women completed the study ( 148 in the vaccine group , 146 in placebo group ) . All initially seronegative subjects in the vaccine group had seroconverted for human papillomavirus-16/18 antibodies by month 7 . Anti-human papillomavirus-16 and anti-human papillomavirus-18 antibody geometric mean titres were 10 422 ( 95 % confidence interval , 8730 - 12 442 ) EL.U/mL and 4649 ( 3975 - 5437 ) EL.U/mL , respectively . High compliance ( 99 % in both groups ) was observed for the three-vaccination course . The frequencies of local injection site reactions were higher in the vaccine than placebo group ; pain being the most common symptom in both groups . Regarding solicited symptoms , fatigue and myalgia were the most frequent in both groups . Five serious adverse events ( four in vaccine group , one in placebo group ) were reported , but all were considered unrelated to the vaccinations . CONCLUSION The human papillomavirus-16/18 AS04-adjuvanted vaccine was highly immunogenic , safe , and generally well tolerated in Chinese women from Hong Kong Objective The study assessed the immunogenicity and safety of human papillomavirus (HPV)-16/18 AS04-adjuvanted cervical cancer vaccine in healthy Korean women aged 15 - 25 years . Methods Phase IIIB , double-blind , r and omised ( 2:1 ) , multi-centre trial was conducted in Korea from June 2007 to March 2008 . The study enrolled 225 women in the HPV ( N=149 ) and placebo ( N=76 ) groups who received three doses of HPV-16/18 AS04-adjuvanted vaccine or placebo ( aluminium hydroxide ) administered intramuscularly at 0 , 1 , and 6 months and were followed until one month post-dose 3 . Serum sample s were collected pre-vaccination and one month post-dose 3 . Safety and reactogenicity data were collected throughout . Results In this trial , 208 women completed the study ( 141 in HPV group ; 67 in placebo group ) . At month 7 , all initially seronegative women had seroconverted for HPV-16 and HPV-18 antibodies with anti-HPV-16 and anti-HPV-18 geometric mean titres of 9,351.4 El . U/mL ( 95 % CI , 8,145.5 to 10,735.8 ) and 4204.1 El . U/mL ( 95 % CI , 3,626.5 to 4,873.6 ) , respectively . Initially seropositive women showed similar increase in geometric mean titre levels . Compliance to the three dose vaccination course was 95.3 % in HPV and 89.5 % in placebo group . Solicited local ( pain ) and general ( fatigue , myalgia or headache ) symptoms were commonly reported in both groups . Three serious adverse events were reported ( two in HPV group ; one in placebo group ) , all unrelated to vaccination by the investigator ; all recovered . Conclusion The HPV-16/18 AS04-adjuvanted vaccine was highly immunogenic with a clinical ly acceptable safety profile in Korean women . This study was in line with previous global studies in Europe , North America , and Brazil . ( Clinical Trials.gov number , NCT 00485732 . 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 ] . ) Cervical cancer of both squamous and adenocarcinoma types is considered virtually 100 % attributable to human papillomavirus ( HPV ) infection . HPV-16 and -18 are the predominant types worldwide accounting for over 70 % of all cervical cancer . Persistent oncogenic HPV infection has been confirmed as one key determinant in the development of cervical precancer ( cervical intraepithelial neoplasia [ CIN ] 2 + ) and cervical cancer . The impact of prophylactic HPV vaccination on the reduction of virological and cytohistological outcomes related to HPV-16 and -18 has been evaluated in clinical trials with the HPV-16/18 AS04-adjuvanted cervical cancer vaccine ( Cervarixtrade mark ) through a Phase IIb study with a long-term follow-up of efficacy up to 5.5 years , and a large Phase III trial in women 15 - 25 years of age . These individual studies include population s with different underlying risk factors , each of which shows high efficacy against both HPV-16/18 persistent infections and CIN2 + . When the two studies are combined and the respective population s are evaluated , vaccine efficacy against HPV-16 and -18-related CIN2 + remains at 100 % . As this vaccine is used over time in universal prophylactic 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: 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 ) AIM India has the highest number of annual incident cases and mortality rates for cervical cancer worldwide . This study was conducted to assess the immunogenicity and safety of human papillomavirus (HPV)-16/18 AS04-adjuvanted cervical cancer vaccine in healthy Indian women aged 18 - 35 years old . METHODS This double-blind , r and omized ( 1:1 ) , controlled and multicenter trial with two parallel groups , the Vaccine and  Placebo groups , included 354 subjects in four centers across India . Subjects were given GlaxoSmithKline 's HPV-16/18 AS04-adjuvanted cervical cancer vaccine or aluminum hydroxide placebo according to a 0 , 1 and 6 month schedule and followed up until month 7 . Serum sample s were drawn at pre-vaccination and at month 7 . Safety data were collected throughout the study . RESULTS A total of 330 subjects completed the study . One month post-Dose 3 , all initially seronegative subjects in the Vaccine group had seroconverted for HPV-16 and HPV-18 antibodies with anti-HPV-16 and anti-HPV-18 geometric mean titer levels of 10226.5 EL.U/ml ( 95 % confidence interval : 8847.1 - 11821.0 ) and 3953.0 EL.U/ml ( 95 % confidence interval : 3421.8 - 4566.8 ) , respectively . Initially seropositive subjects also showed an increase to similar geometric mean titer levels . Six serious adverse events ( two in the Vaccine group and four in the Placebo group ) , all unrelated to vaccination , were reported . Commonly reported solicited local ( injection-site pain ) and general ( fatigue , headache and fever ) symptoms were similar in both groups . Compliance to the three-dose vaccination course was > 97 % . CONCLUSIONS The AS04-adjuvanted HPV-16/18 cervical cancer vaccine was highly immunogenic and generally well-tolerated making it a potential tool for prevention and control of cervical cancer in India OBJECTIVE To assess the immunogenicity and safety of human papillomavirus-16/18 AS04-adjuvanted cervical cancer vaccine in Chinese women aged 18 to 35 years enrolled from Hong Kong . DESIGN Double-blind , r and omised controlled trial with vaccine and placebo groups . SETTING Single-centre study in Hong Kong . PARTICIPANTS Three hundred women enrolled ( 150 per group ) between March 2006 and June 2007 . INTERVENTIONS Subjects received three doses of human papillomavirus-16/18 vaccine or placebo ( aluminium hydroxide ) , administered intramuscularly at 0 , 1 , and 6 months . MAIN OUTCOME MEASURES Human papillomavirus-16/18 seroconversion rates and geometric mean titres at month 7 ( in human papillomavirus-16/18 recipients ) ; reactogenicity and safety ( in all subjects ) . RESULTS A total of 294 women completed the study ( 148 in the vaccine group , 146 in placebo group ) . All initially seronegative subjects in the vaccine group had seroconverted for human papillomavirus-16/18 antibodies by month 7 . Anti-human papillomavirus-16 and anti-human papillomavirus-18 antibody geometric mean titres were 10 422 ( 95 % confidence interval , 8730 - 12 442 ) EL.U/mL and 4649 ( 3975 - 5437 ) EL.U/mL , respectively . High compliance ( 99 % in both groups ) was observed for the three-vaccination course . The frequencies of local injection site reactions were higher in the vaccine than placebo group ; pain being the most common symptom in both groups . Regarding solicited symptoms , fatigue and myalgia were the most frequent in both groups . Five serious adverse events ( four in vaccine group , one in placebo group ) were reported , but all were considered unrelated to the vaccinations . CONCLUSION The human papillomavirus-16/18 AS04-adjuvanted vaccine was highly immunogenic , safe , and generally well tolerated in Chinese women from Hong Kong Objective The study assessed the immunogenicity and safety of human papillomavirus (HPV)-16/18 AS04-adjuvanted cervical cancer vaccine in healthy Korean women aged 15 - 25 years . Methods Phase IIIB , double-blind , r and omised ( 2:1 ) , multi-centre trial was conducted in Korea from June 2007 to March 2008 . The study enrolled 225 women in the HPV ( N=149 ) and placebo ( N=76 ) groups who received three doses of HPV-16/18 AS04-adjuvanted vaccine or placebo ( aluminium hydroxide ) administered intramuscularly at 0 , 1 , and 6 months and were followed until one month post-dose 3 . Serum sample s were collected pre-vaccination and one month post-dose 3 . Safety and reactogenicity data were collected throughout . Results In this trial , 208 women completed the study ( 141 in HPV group ; 67 in placebo group ) . At month 7 , all initially seronegative women had seroconverted for HPV-16 and HPV-18 antibodies with anti-HPV-16 and anti-HPV-18 geometric mean titres of 9,351.4 El . U/mL ( 95 % CI , 8,145.5 to 10,735.8 ) and 4204.1 El . U/mL ( 95 % CI , 3,626.5 to 4,873.6 ) , respectively . Initially seropositive women showed similar increase in geometric mean titre levels . Compliance to the three dose vaccination course was 95.3 % in HPV and 89.5 % in placebo group . Solicited local ( pain ) and general ( fatigue , myalgia or headache ) symptoms were commonly reported in both groups . Three serious adverse events were reported ( two in HPV group ; one in placebo group ) , all unrelated to vaccination by the investigator ; all recovered . Conclusion The HPV-16/18 AS04-adjuvanted vaccine was highly immunogenic with a clinical ly acceptable safety profile in Korean women . This study was in line with previous global studies in Europe , North America , and Brazil . ( Clinical Trials.gov number , NCT 00485732 . 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 ] . ) Cervical cancer of both squamous and adenocarcinoma types is considered virtually 100 % attributable to human papillomavirus ( HPV ) infection . HPV-16 and -18 are the predominant types worldwide accounting for over 70 % of all cervical cancer . Persistent oncogenic HPV infection has been confirmed as one key determinant in the development of cervical precancer ( cervical intraepithelial neoplasia [ CIN ] 2 + ) and cervical cancer . The impact of prophylactic HPV vaccination on the reduction of virological and cytohistological outcomes related to HPV-16 and -18 has been evaluated in clinical trials with the HPV-16/18 AS04-adjuvanted cervical cancer vaccine ( Cervarixtrade mark ) through a Phase IIb study with a long-term follow-up of efficacy up to 5.5 years , and a large Phase III trial in women 15 - 25 years of age . These individual studies include population s with different underlying risk factors , each of which shows high efficacy against both HPV-16/18 persistent infections and CIN2 + . When the two studies are combined and the respective population s are evaluated , vaccine efficacy against HPV-16 and -18-related CIN2 + remains at 100 % . As this vaccine is used over time in universal prophylactic HPV 
    Output:
    