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: This r and omized , partially-blind study ( Clinical Trials.gov registration number NCT00541970 ) evaluated the immunogenicity and safety of 2-dose ( 2D ) schedules of the HPV-16/18 AS04-adjuvanted vaccine . Results to month ( M ) 24 have been reported previously and we now report data to M48 focusing on the licensed vaccine formulation ( 20 μg each of HPV-16 and -18 antigens ) administered at M0,6 compared with the st and ard 3-dose ( 3D ) schedule ( M0,1,6 ) . Healthy females ( age stratified : 9–14 , 15–19 , 20–25 years ) were r and omized to receive 2D at M0,6 ( n = 240 ) or 3D at M0,1,6 ( n = 239 ) . In the according-to- protocol immunogenicity cohort , all initially seronegative subjects seroconverted for HPV-16 and -18 antibodies and remained seropositive up to M48 . For both HPV-16 and -18 , geometric mean antibody titer ( GMT ) ratios ( 3D schedule in women aged 15–25 years divided by 2D schedule in girls aged 9–14 years ) at M36 and M48 were close to 1 , as they were at M7 when non-inferiority was demonstrated . The kinetics of HPV-16 , -18 , -31 , and -45 antibody responses were similar for both groups and HPV-16 and -18 GMTs were substantially higher than natural infection titers . The vaccine had a clinical ly acceptable safety profile in both groups . In summary , antibody responses to a 2D M0,6 schedule of the licensed vaccine formulation in girls aged 9–14 years appeared comparable to the st and ard 3D schedule in women aged 15–25 years up to 4 years after first vaccination . A 2D schedule could facilitate implementation of HPV vaccination programs and improve vaccine coverage and series completion rates & NA ; The authors derived prevalence and incidence figures for cervical human papillomavirus ( HPV ) infections in an unselected Finnish population of women aged 22 . This paper is an epidemiologic study utilizing the mass‐screening program that has been conducted in Finl and for cervical cancer since the early 1960s . The authors estimated the lifetime risk of cervical HPV infections based on the figures in this program and on those derived from a r and om sample of 2,084 ( out of 28,861 ) routine Papanicolaou ( Pap ) smears examined in their laboratory . The mass‐screening program was performed between 1985‐1986 focusing on a total cohort of 22‐year‐old women ( born in 1963 ) in Kuopio province . In 1985 , 2,013 women were invited of which 1,289 attended . One year later , 1,768 women of those 2,013 were reinvited , and the number of women screened at the second round was 1,069 . The routine cervicovaginal Pap smears were taken , including a cell sample from the vagina , exocervix , and endocervix . All smears were screened for the HPV‐induced cytopathic changes by the same cytopathologist . The prevalence of HPV infection among the 22‐year‐old women was about 3 % at the beginning of the follow‐up and about 7 % one year later . The crude annual incidence was 7.0 % . According to the estimates for the life‐time risk , half of the sexually active women would experience at least one HPV infection within 10 years . Up to 79 % of the Finnish females would contract at least one HPV infection between ages 20 and 79 years . This indicates that factors , which are poorly understood at the moment , exist that regulate the development of an invasive carcinoma from a CIS lesion 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 . These results suggest vaccine-induced protection via immune memory , or lower than detectable HPV 18 antibody titers 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 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 This observer-blind study compared the prophylactic human papillomavirus ( HPV ) vaccines , Cervarix ™ ( GlaxoSmithKline ) and Gardasil ® ( Merck ) , by assessing immunogenicity and safety through one month after completion of the three-dose vaccination course . Women ( n=1106 ) were stratified by age ( 18–26 , 27–35 , 36–45 years ) and r and omized ( 1:1 ) to receive Cervarix ™ ( Months 0 , 1 , 6 ) or Gardasil ® ( Months 0 , 2 , 6 ) . At Month 7 after first vaccination , all women in the according-to- protocol cohort who were seronegative/DNA negative before vaccination for the HPV type analyzed had seroconverted for HPV-16 and HPV-18 serum neutralizing antibodies , as measured by pseudovirion-based neutralization assay ( PBNA ) , except for two women aged 27–35 years in the Gardasil ® group who did not seroconvert for HPV-18 ( 98 % ) . Geometric mean titers of serum neutralizing antibodies ranged from 2.3–4.8-fold higher for HPV-16 and 6.8–9.1-fold higher for HPV-18 after vaccination with Cervarix ™ compared with Gardasil ® , across all age strata . In the total vaccinated cohort ( all women who received at least one vaccine dose , regardless of their serological and DNA status prior to vaccination ) , Cervarix ™ induced significantly higher serum neutral 
    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: This r and omized , partially-blind study ( Clinical Trials.gov registration number NCT00541970 ) evaluated the immunogenicity and safety of 2-dose ( 2D ) schedules of the HPV-16/18 AS04-adjuvanted vaccine . Results to month ( M ) 24 have been reported previously and we now report data to M48 focusing on the licensed vaccine formulation ( 20 μg each of HPV-16 and -18 antigens ) administered at M0,6 compared with the st and ard 3-dose ( 3D ) schedule ( M0,1,6 ) . Healthy females ( age stratified : 9–14 , 15–19 , 20–25 years ) were r and omized to receive 2D at M0,6 ( n = 240 ) or 3D at M0,1,6 ( n = 239 ) . In the according-to- protocol immunogenicity cohort , all initially seronegative subjects seroconverted for HPV-16 and -18 antibodies and remained seropositive up to M48 . For both HPV-16 and -18 , geometric mean antibody titer ( GMT ) ratios ( 3D schedule in women aged 15–25 years divided by 2D schedule in girls aged 9–14 years ) at M36 and M48 were close to 1 , as they were at M7 when non-inferiority was demonstrated . The kinetics of HPV-16 , -18 , -31 , and -45 antibody responses were similar for both groups and HPV-16 and -18 GMTs were substantially higher than natural infection titers . The vaccine had a clinical ly acceptable safety profile in both groups . In summary , antibody responses to a 2D M0,6 schedule of the licensed vaccine formulation in girls aged 9–14 years appeared comparable to the st and ard 3D schedule in women aged 15–25 years up to 4 years after first vaccination . A 2D schedule could facilitate implementation of HPV vaccination programs and improve vaccine coverage and series completion rates & NA ; The authors derived prevalence and incidence figures for cervical human papillomavirus ( HPV ) infections in an unselected Finnish population of women aged 22 . This paper is an epidemiologic study utilizing the mass‐screening program that has been conducted in Finl and for cervical cancer since the early 1960s . The authors estimated the lifetime risk of cervical HPV infections based on the figures in this program and on those derived from a r and om sample of 2,084 ( out of 28,861 ) routine Papanicolaou ( Pap ) smears examined in their laboratory . The mass‐screening program was performed between 1985‐1986 focusing on a total cohort of 22‐year‐old women ( born in 1963 ) in Kuopio province . In 1985 , 2,013 women were invited of which 1,289 attended . One year later , 1,768 women of those 2,013 were reinvited , and the number of women screened at the second round was 1,069 . The routine cervicovaginal Pap smears were taken , including a cell sample from the vagina , exocervix , and endocervix . All smears were screened for the HPV‐induced cytopathic changes by the same cytopathologist . The prevalence of HPV infection among the 22‐year‐old women was about 3 % at the beginning of the follow‐up and about 7 % one year later . The crude annual incidence was 7.0 % . According to the estimates for the life‐time risk , half of the sexually active women would experience at least one HPV infection within 10 years . Up to 79 % of the Finnish females would contract at least one HPV infection between ages 20 and 79 years . This indicates that factors , which are poorly understood at the moment , exist that regulate the development of an invasive carcinoma from a CIS lesion 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 . These results suggest vaccine-induced protection via immune memory , or lower than detectable HPV 18 antibody titers 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 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 This observer-blind study compared the prophylactic human papillomavirus ( HPV ) vaccines , Cervarix ™ ( GlaxoSmithKline ) and Gardasil ® ( Merck ) , by assessing immunogenicity and safety through one month after completion of the three-dose vaccination course . Women ( n=1106 ) were stratified by age ( 18–26 , 27–35 , 36–45 years ) and r and omized ( 1:1 ) to receive Cervarix ™ ( Months 0 , 1 , 6 ) or Gardasil ® ( Months 0 , 2 , 6 ) . At Month 7 after first vaccination , all women in the according-to- protocol cohort who were seronegative/DNA negative before vaccination for the HPV type analyzed had seroconverted for HPV-16 and HPV-18 serum neutralizing antibodies , as measured by pseudovirion-based neutralization assay ( PBNA ) , except for two women aged 27–35 years in the Gardasil ® group who did not seroconvert for HPV-18 ( 98 % ) . Geometric mean titers of serum neutralizing antibodies ranged from 2.3–4.8-fold higher for HPV-16 and 6.8–9.1-fold higher for HPV-18 after vaccination with Cervarix ™ compared with Gardasil ® , across all age strata . In the total vaccinated cohort ( all women who received at least one vaccine dose , regardless of their serological and DNA status prior to vaccination ) , Cervarix ™ induced significantly higher serum neutral 
    Output:
    