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: CONTEXT Low- grade squamous intraepithelial lesions ( LSILs ) have been described as a benign cytological consequence of active human papillomavirus ( HPV ) replication . Several studies have reported that certain behavioral and biological risks exist for LSIL , suggesting that HPV alone is not sufficient for the development of LSIL . However , because most of these studies have been cross-sectional , it is not known whether behavioral and biological risks are simply risks for HPV infection itself . OBJECTIVE To prospect ively examine risks of incident HPV infection in HPV-negative females and of incident LSIL development in females with HPV infection . DESIGN Prospect i ve cohort study conducted between 1990 - 2000 , with a median follow-up of 50 months . SETTING AND PARTICIPANTS Females aged 13 to 21 years who attended 2 family planning clinics in the San Francisco bay area ; 496 had prevalent HPV infection and 105 were HPV-negative . MAIN OUTCOME MEASURE Incident development of HPV infection and LSIL , analyzed by various demographic , behavioral , and clinical risk factors . RESULTS Fifty-four incident HPV infections occurred in the 105 females who were HPV-negative at study entry ( median duration of follow-up for those who remained HPV-negative was 26 months ) . Multivariable analysis showed that risks of HPV included sexual behavior ( relative hazard [ RH ] , 10.10 ; 95 % confidence interval [ CI ] , 3.24 - 31.50 per new partner per month ) , history of herpes simplex virus ( RH , 3.54 ; 95 % CI , 1.37 - 9.10 ) , and history of vulvar warts ( RH , 2.73 ; 95 % CI , 1.27 - 5.87 ) . Current use of oral contraceptives had a significantly protective effect ( RH , 0.49 ; 95 % CI , 0.28 - 0.86 ) . Among the 496 individuals who were HPV-positive at baseline or in follow-up , there were 109 incident cases of LSIL during the follow-up interval , with a median follow-up time of 60 months for those who never developed LSIL . Human papillomavirus infection was the most significant risk factor for development of LSIL . The multivariable model showed the following risks for LSIL : HPV infection for less than 1 year ( RH , 7.40 ; 95 % CI , 4.74 - 11.57 ) ; HPV infection for 1 to 2 years ( RH , 10.27 ; 95 % CI , 5.64 - 18.69 ) ; HPV infection for 2 to 3 years ( RH , 6.11 ; 95 % CI , 1.86 - 20.06 ) ; and daily cigarette smoking ( RH , 1.67 ; 95 % CI , 1.12 - 2.48 ) . CONCLUSION Our results indicate distinct risks for HPV and LSIL . In addition , most women with HPV infection in our study did not develop LSIL within a median follow-up period of 60 months . These findings underscore the hypothesis that certain biological risks thought to be associated with LSIL are , in fact , risks for acquisition of HPV . Cigarette smoking was a risk specific to LSIL , supporting the role of tobacco in neoplastic development Background : Two HPV serological assays , the competitive Luminex immunoassay ( cLIA ) , and an enzyme-linked immunoassay ( ELISA ) against HPV16 have been used to define HPV-naïve subcohorts within large HPV vaccination trials . Some of the variation in estimated vaccine efficacies may be due to the differences in these assays used to define the HPV-naïve subgroups . To guide the interpretation of published results , we compared these assays . Methods : Replicate enrollment sera from a stratified sample of 388 unvaccinated women from the control arm of the Costa Rica HPV 16/18 Vaccine Trial were measured for antibodies against HPV16  using cLIA and ELISA . Agreement between the assays was estimated using st and ard and alternative assay cutoffs . Results : Using laboratory-determined seropositivity cutoffs , sampling-adjusted HPV16 seropositivity was 24.8 % by ELISA and 7.2 % by cLIA . Comparing cLIA and ELISA antibody levels based on the st and ard cutoffs , overall agreement was 53 % ( positive-agreement = 49 % ) . The poor agreement was mainly driven by the higher sensitivity of the ELISA than cLIA , result ing in 30 % of the ELISA-positive sample that were cLIA-negative ( none of the ELISA-negatives were cLIA-positive ) . Increasing ELISA cutoff to 54 ELISA units (EU)/mL ( the level which maximized agreement with cLIA ; ELISA st and ard cutoff is 8 EU/mL ) result ed in higher agreement ( overall agreement = 91 % ; positive agreement = 78 % ) . Conclusions : ELISA and cLIA are different from each other based on the laboratory-determined cutoff . Increasing ELISA cutoff increased agreement with cLIA , which could facilitate comparisons among studies that use different assays . Impact : Keeping cLIA at the laboratory-determined cutoff but altering ELISA cutoff for seropositivity might facilitate vaccine efficacy comparisons in the naïve cohorts defined by cLIA . Cancer Epidemiol Biomarkers Prev ; 21(9 ) ; 1547–54 . © 2012 AACR 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 ) The prevalence of HPV infection in Latin America is among the highest in the world . A quadrivalent ( types 6/11/16/18 ) human papillomavirus L1 virus-like-particle vaccine has been shown to be 95 - 100 % effective in preventing HPV 6/11/16/18-related cervical and genital disease in women naive to vaccine HPV types . A total of 6,004 female subjects aged 9 - 24 were recruited from Brazil , Mexico , Colombia , Costa Rica , Guatemala and Peru . Subjects were r and omized to immunization with intramuscular ( deltoid ) injections of HPV vaccine or placebo at enrollment ( day 1 ) , month 2 and month 6 . Among vaccinated subjects in the per- protocol population from Latin America , quadrivalent HPV vaccine was 92.8 and 100 % effective in preventing cervical intraepithelial neoplasia and external genital lesions related to vaccine HPV types , respectively . These data support vaccination of adolescents and young adults in the region , which is expected to greatly reduce the burden of cervical and genital cancers , precancers and genital warts 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 efficacy of the quadrivalent Human Papillomavirus ( HPV ) vaccine is thought to be mediated by humoral immunity . We evaluated the correlation between quadrivalent HPV vaccine-induced serum anti-HPV responses and efficacy . 17,622 women were vaccinated at day 1 , and months 2 and 6 . At day 1 and at 6 - 12 months intervals for up to 48 months , subjects underwent Papanicolaou and genital HPV testing . No immune correlate of protection could be found due to low number of cases . Although 40 % of vaccine subjects were anti-HPV 18 seronegative at end-of- study , efficacy against HPV 18-related disease remained high ( 98.4 % ; 95 % CI : 90.5 - 100.0 ) despite high attack rates in the placebo group . 
    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: CONTEXT Low- grade squamous intraepithelial lesions ( LSILs ) have been described as a benign cytological consequence of active human papillomavirus ( HPV ) replication . Several studies have reported that certain behavioral and biological risks exist for LSIL , suggesting that HPV alone is not sufficient for the development of LSIL . However , because most of these studies have been cross-sectional , it is not known whether behavioral and biological risks are simply risks for HPV infection itself . OBJECTIVE To prospect ively examine risks of incident HPV infection in HPV-negative females and of incident LSIL development in females with HPV infection . DESIGN Prospect i ve cohort study conducted between 1990 - 2000 , with a median follow-up of 50 months . SETTING AND PARTICIPANTS Females aged 13 to 21 years who attended 2 family planning clinics in the San Francisco bay area ; 496 had prevalent HPV infection and 105 were HPV-negative . MAIN OUTCOME MEASURE Incident development of HPV infection and LSIL , analyzed by various demographic , behavioral , and clinical risk factors . RESULTS Fifty-four incident HPV infections occurred in the 105 females who were HPV-negative at study entry ( median duration of follow-up for those who remained HPV-negative was 26 months ) . Multivariable analysis showed that risks of HPV included sexual behavior ( relative hazard [ RH ] , 10.10 ; 95 % confidence interval [ CI ] , 3.24 - 31.50 per new partner per month ) , history of herpes simplex virus ( RH , 3.54 ; 95 % CI , 1.37 - 9.10 ) , and history of vulvar warts ( RH , 2.73 ; 95 % CI , 1.27 - 5.87 ) . Current use of oral contraceptives had a significantly protective effect ( RH , 0.49 ; 95 % CI , 0.28 - 0.86 ) . Among the 496 individuals who were HPV-positive at baseline or in follow-up , there were 109 incident cases of LSIL during the follow-up interval , with a median follow-up time of 60 months for those who never developed LSIL . Human papillomavirus infection was the most significant risk factor for development of LSIL . The multivariable model showed the following risks for LSIL : HPV infection for less than 1 year ( RH , 7.40 ; 95 % CI , 4.74 - 11.57 ) ; HPV infection for 1 to 2 years ( RH , 10.27 ; 95 % CI , 5.64 - 18.69 ) ; HPV infection for 2 to 3 years ( RH , 6.11 ; 95 % CI , 1.86 - 20.06 ) ; and daily cigarette smoking ( RH , 1.67 ; 95 % CI , 1.12 - 2.48 ) . CONCLUSION Our results indicate distinct risks for HPV and LSIL . In addition , most women with HPV infection in our study did not develop LSIL within a median follow-up period of 60 months . These findings underscore the hypothesis that certain biological risks thought to be associated with LSIL are , in fact , risks for acquisition of HPV . Cigarette smoking was a risk specific to LSIL , supporting the role of tobacco in neoplastic development Background : Two HPV serological assays , the competitive Luminex immunoassay ( cLIA ) , and an enzyme-linked immunoassay ( ELISA ) against HPV16 have been used to define HPV-naïve subcohorts within large HPV vaccination trials . Some of the variation in estimated vaccine efficacies may be due to the differences in these assays used to define the HPV-naïve subgroups . To guide the interpretation of published results , we compared these assays . Methods : Replicate enrollment sera from a stratified sample of 388 unvaccinated women from the control arm of the Costa Rica HPV 16/18 Vaccine Trial were measured for antibodies against HPV16  using cLIA and ELISA . Agreement between the assays was estimated using st and ard and alternative assay cutoffs . Results : Using laboratory-determined seropositivity cutoffs , sampling-adjusted HPV16 seropositivity was 24.8 % by ELISA and 7.2 % by cLIA . Comparing cLIA and ELISA antibody levels based on the st and ard cutoffs , overall agreement was 53 % ( positive-agreement = 49 % ) . The poor agreement was mainly driven by the higher sensitivity of the ELISA than cLIA , result ing in 30 % of the ELISA-positive sample that were cLIA-negative ( none of the ELISA-negatives were cLIA-positive ) . Increasing ELISA cutoff to 54 ELISA units (EU)/mL ( the level which maximized agreement with cLIA ; ELISA st and ard cutoff is 8 EU/mL ) result ed in higher agreement ( overall agreement = 91 % ; positive agreement = 78 % ) . Conclusions : ELISA and cLIA are different from each other based on the laboratory-determined cutoff . Increasing ELISA cutoff increased agreement with cLIA , which could facilitate comparisons among studies that use different assays . Impact : Keeping cLIA at the laboratory-determined cutoff but altering ELISA cutoff for seropositivity might facilitate vaccine efficacy comparisons in the naïve cohorts defined by cLIA . Cancer Epidemiol Biomarkers Prev ; 21(9 ) ; 1547–54 . © 2012 AACR 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 ) The prevalence of HPV infection in Latin America is among the highest in the world . A quadrivalent ( types 6/11/16/18 ) human papillomavirus L1 virus-like-particle vaccine has been shown to be 95 - 100 % effective in preventing HPV 6/11/16/18-related cervical and genital disease in women naive to vaccine HPV types . A total of 6,004 female subjects aged 9 - 24 were recruited from Brazil , Mexico , Colombia , Costa Rica , Guatemala and Peru . Subjects were r and omized to immunization with intramuscular ( deltoid ) injections of HPV vaccine or placebo at enrollment ( day 1 ) , month 2 and month 6 . Among vaccinated subjects in the per- protocol population from Latin America , quadrivalent HPV vaccine was 92.8 and 100 % effective in preventing cervical intraepithelial neoplasia and external genital lesions related to vaccine HPV types , respectively . These data support vaccination of adolescents and young adults in the region , which is expected to greatly reduce the burden of cervical and genital cancers , precancers and genital warts 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 efficacy of the quadrivalent Human Papillomavirus ( HPV ) vaccine is thought to be mediated by humoral immunity . We evaluated the correlation between quadrivalent HPV vaccine-induced serum anti-HPV responses and efficacy . 17,622 women were vaccinated at day 1 , and months 2 and 6 . At day 1 and at 6 - 12 months intervals for up to 48 months , subjects underwent Papanicolaou and genital HPV testing . No immune correlate of protection could be found due to low number of cases . Although 40 % of vaccine subjects were anti-HPV 18 seronegative at end-of- study , efficacy against HPV 18-related disease remained high ( 98.4 % ; 95 % CI : 90.5 - 100.0 ) despite high attack rates in the placebo group . 
    Output:
    