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 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 ) Human papillomavirus ( HPV ) infection causes cervical cancer and genital warts . Young women ( 1106 ) were r and omized to receive one of three formulations of a quadrivalent HPV ( Types 6/11/16/18 ) L1 virus-like particle ( VLP ) vaccine or one of two placebo formulations . The goal was to assess vaccine safety and immunogenicity in baseline HPV 6/11/16 or 18-naïve and previously infected subjects . All three formulations were highly immunogenic . At Month 2 ( postdose 1 ) , among women with vaccine-type antibodies at baseline , vaccine-induced anti-HPV responses were approximately 12- to 26-fold higher than those observed in baseline-naïve women , suggesting an anamnestic response . Following an initial , similar sized decline , anti-HPV responses plateaued and remained stable through end-of- study ( 3.0 years ) . No vaccine-related serious adverse experiences were reported HPV-023 ( NCT00518336 ; Clinical Trial.gov ) is a long-term follow-up of an initial double-blind , r and omized ( 1:1 ) , placebo-controlled study ( HPV-001 , NCT00689741 ) evaluating the efficacy against  human papillomavirus (HPV)-16/18 infection and associated cyto-histopathological abnormalities  , persistence of immunogenicity , and safety of the HPV-16/18 AS04-adjuvanted vaccine . Among the women , aged 15–25 years , enrolled in HPV-001 and who participated in the follow-up study HPV-007 ( NCT00120848 ) , a subset of 437 women from five Brazilian centers participated in this 36-month long-term follow-up ( HPV-023 ) for a total of 113 months ( 9.4 years ) . During HPV-023 , anti-HPV-16/18 antibodies were measured annually by enzyme-linked immunosorbent assay ( ELISA ) and pseudovirion-based neutralisation assay ( PBNA ) . Cervical sample s were tested for HPV DNA every 6 months , and cyto-pathological examinations were performed annually . During HPV-023 , no new HPV-16/18-associated infections and cyto-histopathological abnormalities occurred in the vaccine group . Vaccine efficacy ( VE ) against HPV-16/18 incident infection was 100 % ( 95%CI : 66.1 , 100 ) . Over the 113 months ( 9.4 years ) , VE was 95.6 % ( 86.2 , 99.1 ; 3/50 cases in vaccine and placebo groups , respectively ) against incident infection , 100 % ( 84·1 , 100 ; 0/21 ) against 6-month persistent infection ( PI ) ; 100 % ( 61·4 , 100 ; 0/10 ) against 12-month PI ; 97·1 % ( 82.5 , 99.9 ; 1/30 ) against ≥ ASC-US ; 95·0 % ( 68.0 , 99.9 ; 1/18 ) against ≥ LSIL ; 100 % ( 45.2 , 100 ; 0/8 ) against CIN1 + ; and 100 % ( –128.1 , 100 ; 0/3 ) against CIN2 + associated with HPV-16/18 . All vaccinees remained seropositive to HPV-16/18 , with antibody titers remaining several folds above natural infection levels , as measured by ELISA and PBNA . There were no safety concerns . To date , these data represent the longest follow-up reported for a licensed HPV vaccine BACKGROUND The 9-valent human papillomavirus ( HPV ) ( 9vHPV ) vaccine targets the four HPV types ( 6/11/16/18 ) covered by the licensed quadrivalent HPV ( qHPV ) vaccine and five additional types ( 31/33/45/52/58 ) . A large outcome trial of 9vHPV vaccine was conducted . METHODS An active control ( qHPV vaccine ) was used because a placebo is not ethically acceptable . Since qHPV vaccine is ( and 9vHPV vaccine was anticipated to be ) highly efficacious against HPV 6/11/16/18 , low incidence of HPV 6/11/16/18-associated disease was expected . Consequently , an efficacy comparison of 9vHPV versus qHPV vaccine for HPV 6/11/16/18 would have been prohibitively large in size . Moreover , no minimum antibody level predicting protection against infection or disease is defined for HPV vaccination . As an alternative approach , the two vaccines were compared using immunogenicity bridging for HPV 6/11/16/18 and clinical efficacy for HPV 31/33/45/52/58 . RESULTS The two co- primary objectives were to demonstrate : ( 1 ) non-inferior anti-HPV 6/11/16/18 antibody response ; and ( 2 ) superior efficacy in HPV 31/33/45/52/58-related clinical outcome , for 9vHPV vaccine versus qHPV vaccine . For HPV 6/11/16/18 , supportive analyses included a non-inferiority assessment of the percent risk reduction ( compared to historical placebo ) for 9vHPV versus qHPV vaccine . CONCLUSIONS A Phase III study of 9vHPV vaccine was successfully implemented . Experience from this study design may be applicable when developing a multivalent vaccine covering the same serotypes as an existing vaccine plus additional serotypes and there is no immune correlate of protection . Also , this study established that efficacy of a new HPV vaccine may be demonstrated using immunogenicity endpoints , which may open new options in HPV vaccine development OBJECTIVES To assess the safety and immunogenicity of the investigational 9-valent ( 6/11/16/18/31/33/45/52/58 ) HPV ( 9vHPV ) vaccine in prior recipients of a 3-dose regimen of quadrivalent ( 6/11/16/18 ) HPV ( qHPV ) vaccine . METHODS V503 - 006 was a r and omized , double-blinded , safety/tolerability and immunogenicity study of the 9vHPV vaccine in females 12 - 26 years of age who were previously vaccinated with qHPV vaccine . Subjects were r and omized in a 2:1 ratio to receive 3 doses of 9vHPV vaccine ( n=618 ) or saline placebo ( n=306 ) at day 1 , month 2 , and month 6 . Systemic , injection-site and serious adverse experiences ( AEs ) were monitored . Serum sample s were collected at day 1 , month 2 , and month 7 . Anti-HPV 6/11/16/18/31/33/45/52/58 titers were measured using the 9-valent HPV competitive Luminex Immunoassay ( cLIA ) . RESULTS The frequency of injection-site AEs ( days 1 - 5 following any vaccination ) was higher in the 9vHPV vaccine group than in the placebo group ( 91.1 % and 43.9 % , respectively ) . The frequencies of vaccine-related systemic AEs ( days 1 - 15 following any vaccination ) were generally comparable between the 2 groups ( 30.6 % in the 9vHPV vaccine group , and 25.9 % in the placebo group ) . One vaccine-related serious AE was reported in each of the 9vHPV vaccine and placebo groups . Few subjects ( 9vHPV=0.5 % ; placebo=0 % ) discontinued due to an AE . At 4 weeks post-dose 3 , over 98 % of subjects in the 9vHPV vaccine group were seropositive for HPV types 31/33/45/52/58 , with marked elevations in cLIA geometric mean titers ( GMTs ) to these HPV types . Anti-HPV 31/33/45/52/58 GMTs were lower than in subjects administered 9vHPV vaccine who had not previously received qHPV vaccine ( based on cross- study analyses ) ; the clinical significance of this difference is unknown . CONCLUSIONS Administration of a 3-dose regimen of 9vHPV vaccine to adolescent girls and young women 12 - 26 years of age who are prior qHPV vaccine recipients is highly immunogenic with respect to HPV types 31/33/45/52/58 and generally well tolerated Background : Worldwide , human papillomavirus ( HPV ) 16 and 18 represents 70 % of high-risk ( HR ) HPV found in cervical cancer . However HIV-positive women are more frequently infected by HRHPV other than HPV 16 or 18 ( OHR ) . We aim ed to analyse the HRHPV genotype distribution in a cohort of HIV-positive women and to estimate the potential protection offered by the different HPV vaccines . Methods : HRHPV genotypes by PCR and cytology were assessed in cervical sample s from 508 HIV-positive women prospect ively followed in Brussels . Results : Women characteristics were as follows : African origin ( 84 % ) , median age 42 years , median CD4 + T 555/&mgr;l , 89 % under combined antiretroviral therapy and 73 % with HIVRNA less than 20 copies/ml .  HRHPV prevalence was 23 % ( 116/508 ) : 38 % had abnormal cytology , 76 % 
    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 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 ) Human papillomavirus ( HPV ) infection causes cervical cancer and genital warts . Young women ( 1106 ) were r and omized to receive one of three formulations of a quadrivalent HPV ( Types 6/11/16/18 ) L1 virus-like particle ( VLP ) vaccine or one of two placebo formulations . The goal was to assess vaccine safety and immunogenicity in baseline HPV 6/11/16 or 18-naïve and previously infected subjects . All three formulations were highly immunogenic . At Month 2 ( postdose 1 ) , among women with vaccine-type antibodies at baseline , vaccine-induced anti-HPV responses were approximately 12- to 26-fold higher than those observed in baseline-naïve women , suggesting an anamnestic response . Following an initial , similar sized decline , anti-HPV responses plateaued and remained stable through end-of- study ( 3.0 years ) . No vaccine-related serious adverse experiences were reported HPV-023 ( NCT00518336 ; Clinical Trial.gov ) is a long-term follow-up of an initial double-blind , r and omized ( 1:1 ) , placebo-controlled study ( HPV-001 , NCT00689741 ) evaluating the efficacy against  human papillomavirus (HPV)-16/18 infection and associated cyto-histopathological abnormalities  , persistence of immunogenicity , and safety of the HPV-16/18 AS04-adjuvanted vaccine . Among the women , aged 15–25 years , enrolled in HPV-001 and who participated in the follow-up study HPV-007 ( NCT00120848 ) , a subset of 437 women from five Brazilian centers participated in this 36-month long-term follow-up ( HPV-023 ) for a total of 113 months ( 9.4 years ) . During HPV-023 , anti-HPV-16/18 antibodies were measured annually by enzyme-linked immunosorbent assay ( ELISA ) and pseudovirion-based neutralisation assay ( PBNA ) . Cervical sample s were tested for HPV DNA every 6 months , and cyto-pathological examinations were performed annually . During HPV-023 , no new HPV-16/18-associated infections and cyto-histopathological abnormalities occurred in the vaccine group . Vaccine efficacy ( VE ) against HPV-16/18 incident infection was 100 % ( 95%CI : 66.1 , 100 ) . Over the 113 months ( 9.4 years ) , VE was 95.6 % ( 86.2 , 99.1 ; 3/50 cases in vaccine and placebo groups , respectively ) against incident infection , 100 % ( 84·1 , 100 ; 0/21 ) against 6-month persistent infection ( PI ) ; 100 % ( 61·4 , 100 ; 0/10 ) against 12-month PI ; 97·1 % ( 82.5 , 99.9 ; 1/30 ) against ≥ ASC-US ; 95·0 % ( 68.0 , 99.9 ; 1/18 ) against ≥ LSIL ; 100 % ( 45.2 , 100 ; 0/8 ) against CIN1 + ; and 100 % ( –128.1 , 100 ; 0/3 ) against CIN2 + associated with HPV-16/18 . All vaccinees remained seropositive to HPV-16/18 , with antibody titers remaining several folds above natural infection levels , as measured by ELISA and PBNA . There were no safety concerns . To date , these data represent the longest follow-up reported for a licensed HPV vaccine BACKGROUND The 9-valent human papillomavirus ( HPV ) ( 9vHPV ) vaccine targets the four HPV types ( 6/11/16/18 ) covered by the licensed quadrivalent HPV ( qHPV ) vaccine and five additional types ( 31/33/45/52/58 ) . A large outcome trial of 9vHPV vaccine was conducted . METHODS An active control ( qHPV vaccine ) was used because a placebo is not ethically acceptable . Since qHPV vaccine is ( and 9vHPV vaccine was anticipated to be ) highly efficacious against HPV 6/11/16/18 , low incidence of HPV 6/11/16/18-associated disease was expected . Consequently , an efficacy comparison of 9vHPV versus qHPV vaccine for HPV 6/11/16/18 would have been prohibitively large in size . Moreover , no minimum antibody level predicting protection against infection or disease is defined for HPV vaccination . As an alternative approach , the two vaccines were compared using immunogenicity bridging for HPV 6/11/16/18 and clinical efficacy for HPV 31/33/45/52/58 . RESULTS The two co- primary objectives were to demonstrate : ( 1 ) non-inferior anti-HPV 6/11/16/18 antibody response ; and ( 2 ) superior efficacy in HPV 31/33/45/52/58-related clinical outcome , for 9vHPV vaccine versus qHPV vaccine . For HPV 6/11/16/18 , supportive analyses included a non-inferiority assessment of the percent risk reduction ( compared to historical placebo ) for 9vHPV versus qHPV vaccine . CONCLUSIONS A Phase III study of 9vHPV vaccine was successfully implemented . Experience from this study design may be applicable when developing a multivalent vaccine covering the same serotypes as an existing vaccine plus additional serotypes and there is no immune correlate of protection . Also , this study established that efficacy of a new HPV vaccine may be demonstrated using immunogenicity endpoints , which may open new options in HPV vaccine development OBJECTIVES To assess the safety and immunogenicity of the investigational 9-valent ( 6/11/16/18/31/33/45/52/58 ) HPV ( 9vHPV ) vaccine in prior recipients of a 3-dose regimen of quadrivalent ( 6/11/16/18 ) HPV ( qHPV ) vaccine . METHODS V503 - 006 was a r and omized , double-blinded , safety/tolerability and immunogenicity study of the 9vHPV vaccine in females 12 - 26 years of age who were previously vaccinated with qHPV vaccine . Subjects were r and omized in a 2:1 ratio to receive 3 doses of 9vHPV vaccine ( n=618 ) or saline placebo ( n=306 ) at day 1 , month 2 , and month 6 . Systemic , injection-site and serious adverse experiences ( AEs ) were monitored . Serum sample s were collected at day 1 , month 2 , and month 7 . Anti-HPV 6/11/16/18/31/33/45/52/58 titers were measured using the 9-valent HPV competitive Luminex Immunoassay ( cLIA ) . RESULTS The frequency of injection-site AEs ( days 1 - 5 following any vaccination ) was higher in the 9vHPV vaccine group than in the placebo group ( 91.1 % and 43.9 % , respectively ) . The frequencies of vaccine-related systemic AEs ( days 1 - 15 following any vaccination ) were generally comparable between the 2 groups ( 30.6 % in the 9vHPV vaccine group , and 25.9 % in the placebo group ) . One vaccine-related serious AE was reported in each of the 9vHPV vaccine and placebo groups . Few subjects ( 9vHPV=0.5 % ; placebo=0 % ) discontinued due to an AE . At 4 weeks post-dose 3 , over 98 % of subjects in the 9vHPV vaccine group were seropositive for HPV types 31/33/45/52/58 , with marked elevations in cLIA geometric mean titers ( GMTs ) to these HPV types . Anti-HPV 31/33/45/52/58 GMTs were lower than in subjects administered 9vHPV vaccine who had not previously received qHPV vaccine ( based on cross- study analyses ) ; the clinical significance of this difference is unknown . CONCLUSIONS Administration of a 3-dose regimen of 9vHPV vaccine to adolescent girls and young women 12 - 26 years of age who are prior qHPV vaccine recipients is highly immunogenic with respect to HPV types 31/33/45/52/58 and generally well tolerated Background : Worldwide , human papillomavirus ( HPV ) 16 and 18 represents 70 % of high-risk ( HR ) HPV found in cervical cancer . However HIV-positive women are more frequently infected by HRHPV other than HPV 16 or 18 ( OHR ) . We aim ed to analyse the HRHPV genotype distribution in a cohort of HIV-positive women and to estimate the potential protection offered by the different HPV vaccines . Methods : HRHPV genotypes by PCR and cytology were assessed in cervical sample s from 508 HIV-positive women prospect ively followed in Brussels . Results : Women characteristics were as follows : African origin ( 84 % ) , median age 42 years , median CD4 + T 555/&mgr;l , 89 % under combined antiretroviral therapy and 73 % with HIVRNA less than 20 copies/ml .  HRHPV prevalence was 23 % ( 116/508 ) : 38 % had abnormal cytology , 76 % 
    Output:
    