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 Most squamous cell anal cancers and precancerous lesions are attributed to human papillomavirus ( HPV ) infection . By preventing HPV infection , quadrivalent HPV vaccine ( qHPV ) reduces risk of anal cancer/precancerous lesions in young men who have sex with men ( MSM ) without history of anal cancer/precancerous lesions . In our practice , many persons with history of precancerous anal lesions or high- grade anal intraepithelial neoplasia ( HGAIN ) have been vaccinated electively . We determined whether qHPV is effective at preventing recurrence of HGAIN . METHODS This nonconcurrent cohort study evaluated 202 patients with a history of previously treated HGAIN . Eighty-eight patients were vaccinated , and 114 patients were unvaccinated . We determined the recurrence rate of histologic HGAIN in vaccinated versus unvaccinated patients . RESULTS During 340.4 person-years follow-up , 12 ( 13.6 % ) vaccinated patients and 35 ( 30.7 % ) unvaccinated patients developed recurrent HGAIN . Multivariable hazards ratio ( HR ) analysis showed testing positive for oncogenic HPV genotypes within 8 months before study entry was associated with increased risk of recurrent HGAIN at 2 years after study entry ( HR 4.06 ; 95 % confidence interval [ CI ] , 1.58 - 10.40 ; P = .004 ) , and qHPV was associated with decreased risk of recurrent HGAIN ( HR .50 ; 95 % CI , .26-.98 ; P = .04 ) . Among patients infected with oncogenic HPV , qHPV was associated with decreased risk of recurrent HGAIN at 2 years after study entry ( HR .47 ; 95 % CI , .22 - 1.00 ; P = .05 ) . CONCLUSIONS qHPV significantly reduces HGAIN recurrence  among MSM and may be an effective posttreatment adjuvant form of therapy . A r and omized controlled trial is needed to confirm these results Objective Due to long lag time between infection/cancer diagnoses human papillomavirus ( HPV ) vaccination programs will deliver vaccine efficacy ( VE ) estimates against cancer end-points late . Cancer registry follow-up of population -based , r and omised trial cohorts of vaccinated and unvaccinated women was undertaken for the estimation of VE against cervical intraepithelial neoplasia grade three and invasive cancer ( CIN3 + ) . Methods We report interim results with 98 561 person years of Finnish Cancer Registry -based follow-up of individually and /or cluster r and omised cohorts of HPV-16/18 vaccinated and unvaccinated adolescent women enrolled in June 2003/2005 , and between May 2004 and April 2005 , respectively . The cohorts comprised 15 627 18- to 19-year-old unvaccinated women ( NCT01393470 ) , and 2 401 and 64 16- to 17-year-old HPV-16/18 vaccinated women participating the PATRICIA ( NCT00122681 ) and HPV-012 ( NCT00169494 ) trials , respectively . The age-aligned passive follow-up started 6 months after the clinical trials ’ end . Results During the follow-up of 4.5 to 10 years post enrolment we identified 75 cases of cervical intraepithelial neoplasia grade 3 ( CIN3 ) and 4 cases of invasive cervical cancer ( ICC ) in the unvaccinated cohort , and 4 CIN3 cases in the HPV-16/18 vaccinated women . Diagnostic blocks were available for HPV typing from 87 % of the cases . CIN3 + lesions were detectable in 54 cases . HPV16 was found in 26 of 50 unvaccinated CIN3 + cases , and in 3 CIN3 + cases in the HPV-16/18 vaccinated women . The latter were all baseline positive for cervical HPV16 DNA . Baseline data was not available for the unvaccinated women . Intention-to-treat VE against any CIN3 + was 66 % ( 95 % CI 8 , 88 ) . Conclusions Ten years post vaccination the AS04-adjuvanted HPV-16/18 vaccine shows continued efficacy against CIN3 + irrespectively of HPV type . Vaccine efficacy was not observed in baseline HPV16 DNA positive subjects . Trial registration number NCT01393470 Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more BACKGROUND Infection with human papillomavirus ( HPV ) and diseases caused by HPV are common in boys and men . We report on the safety of a quadrivalent vaccine ( active against HPV types 6 , 11 , 16 , and 18 ) and on its efficacy in preventing the development of external genital lesions and anogenital HPV infection in boys and men . METHODS We enrolled 4065 healthy boys and men 16 to 26 years of age , from 18 countries in a r and omized , placebo-controlled , double-blind trial . The primary efficacy objective was to show that the quadrivalent HPV vaccine reduced the incidence of external genital lesions related to HPV-6 , 11 , 16 , or 18 . Efficacy analyses were conducted in a per- protocol population , in which subjects received all three vaccinations and were negative for relevant HPV types at enrollment , and in an intention-to-treat population , in which subjects received vaccine or placebo , regardless of baseline HPV status . RESULTS In the intention-to-treat population , 36 external genital lesions were seen in the vaccine group as compared with 89 in the placebo group , for an observed efficacy of 60.2 % ( 95 % confidence interval [ CI ] , 40.8 to 73.8 ) ; the efficacy was 65.5 % ( 95 % CI , 45.8 to 78.6 ) for lesions related to HPV-6 , 11 , 16 , or 18 . In the per- protocol population , efficacy against lesions related to HPV-6 , 11 , 16 , or 18 was 90.4 % ( 95 % CI , 69.2 to 98.1 ) . Efficacy with respect to persistent infection with HPV-6 , 11 , 16 , or 18 and detection of related DNA at any time was 47.8 % ( 95 % CI , 36.0 to 57.6 ) and 27.1 % ( 95 % CI , 16.6 to 36.3 ) , respectively , in the intention-to-treat population and 85.6 % ( 97.5 % CI , 73.4 to 92.9 ) and 44.7 % ( 95 % CI , 31.5 to 55.6 ) in the per- protocol population . Injection-site pain was significantly more frequent among subjects receiving quadrivalent HPV vaccine than among those receiving placebo ( 57 % vs. 51 % , P<0.001 ) . CONCLUSIONS Quadrivalent HPV vaccine prevents infection with HPV-6 , 11 , 16 , and 18 and the development of related external genital  lesions in males 16 to 26 years of age . ( Funded by Merck and others ; Clinical Trials.gov number , NCT00090285 . ) Non-r and omised studies of the effects of interventions are critical to many areas of healthcare evaluation , but their results may be biased . It is therefore important to underst and and appraise their strengths and weaknesses . We developed ROBINS-I ( “ Risk Of Bias In Non-r and omised Studies - of Interventions ” ) , a new tool for evaluating risk of bias in estimates of the comparative effectiveness ( harm or benefit ) of interventions from studies that did not use r and omisation  to allocate units ( individuals or clusters of individuals ) to comparison groups . The tool will be particularly useful to those undertaking systematic review s that include non-r and omised studies Background The quadrivalent human papillomavirus vaccine ( qHPV ) is FDA -approved for use in males 9 to 26 years old to prevent anogenital condyloma . The objective of this study is to determine if qHPV is effective at preventing anal condyloma among men who have sex with men ( MSM ) aged 26 years and older . Methods This post-hoc analysis of a nonconcurrent cohort study evaluated 210 patients without history of anal condyloma and 103 patients with previously-treated anal condyloma recurrence-free for at least 12 months prior to vaccination/time zero . We determined the rate of anal condyloma development in vaccinated versus unvaccinated patients . Results 313 patients with mean age 42 years were followed for median 981 days . During 773.6 person-years follow-up , condyloma developed in 10 ( 8.6 % ) vaccinated patients ( incidence of 3.7 per 100 person-years ) and 37 ( 18.8 % ) unvaccinated patients ( incidence 7.3 per 100 person-years ; p = 0.05 ) . Multivariable hazards ratio showed that qHPV was associated with decreased risk of anal condyloma development ( HR 0.45 ; 95 % CI 0.22–0.92 ; p = 0.03 ) . History of anal condyloma was associated with increased risk of anal condyloma development ( HR 2.28 ; 95 % CI 1.28–4.05 ; p = 0.005 ) , as was infection with oncogenic HPV ( HR 3.87 ; 95 % CI 1.66–9.03 ; p = 0.002 ) . Conclusions Among MSM 26 years of age and older with and without history of anal condyloma , qHPV reduces the risk of anal condyloma development . A r and omized controlled trial is needed to confirm these findings in this age group INTRODUCTION Human papillomavirus ( HPV ) is one of the most common sexually transmitted infections and is the cause of several different diseases in men and women . Although little is known about HPV infection in men , they are also in the risk group of HPV infection and play an important role in transmitting the virus to women . AIM To define the efficacy of the HPV vaccine through cross-immunization and its role in clearance of HPV infection , and to assess infection-associated factors in men . METHODS This prospect i ve r and omized clinical study enrolled 171 evaluable men with genital warts between June 2009 and October 2013 . After the initial treatment intervention , 91 patients were r and omly assigned to receive HPV vaccine in three doses . Eighty patients were in the  control  ( unvaccinated ) group . One hundred-eleven men were single and 60 men were married . Patients who had previous treatment for pre-existing warts and medical disorders that needed chronic treatment or immunosuppression were not included in the r and omization . Also 29 men with follow-up less than 12 months and incomplete vaccination were not included . MAIN OUTCOME MEASURES The patients were assessed regarding age , condom use , marital status , number of visible genital warts , and smoking status . Post-treatment follow-up was monthly up to 12th month . RESULTS Mean age was 34 ± 7.6 . One hundred fifteen patients were smokers . For the recurrence of warts , age , smoking , vaccination status were insignificant and marital status was significant in the univariable analysis ; only marital status preserved significance ( HR : 2.0 CI:1.29 - 3.12 P = 0.002 ) in the multivariable analysis including vaccination status , marital status , and smoking . CONCLUSION Among the investigated factors vaccination status was not but marital status significantly influenced wart recurrence . Married men had more recurrences in our population . Larger multicenter r and omized clinical trials are lacking and seriously required to investigate the therapeutic effect of current quadrivalent HPV vaccine in genital warts BACKGROUND The rate of anal cancer is increasing among both women and men , particularly men who have sex with men . Caused by infection with human papillomavirus ( HPV ) , primarily HPV type 16 or 18 , anal cancer is preceded by high- grade anal intraepithelial neoplasia ( grade 2 or 3 ) . We studied the safety and efficacy of quadrivalent HPV vaccine ( qHPV ) against anal intraepithelial neoplasia associated with HPV-6 , 11 , 16 , or 18 infection in men who have sex with men . METHODS In a sub study of a larger double-blind study , we r and omly assigned 602 healthy men who have sex with men , 16 to 26 years of age , to receive either qHPV or placebo . The primary efficacy objective was prevention of anal intraepith 
    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 Most squamous cell anal cancers and precancerous lesions are attributed to human papillomavirus ( HPV ) infection . By preventing HPV infection , quadrivalent HPV vaccine ( qHPV ) reduces risk of anal cancer/precancerous lesions in young men who have sex with men ( MSM ) without history of anal cancer/precancerous lesions . In our practice , many persons with history of precancerous anal lesions or high- grade anal intraepithelial neoplasia ( HGAIN ) have been vaccinated electively . We determined whether qHPV is effective at preventing recurrence of HGAIN . METHODS This nonconcurrent cohort study evaluated 202 patients with a history of previously treated HGAIN . Eighty-eight patients were vaccinated , and 114 patients were unvaccinated . We determined the recurrence rate of histologic HGAIN in vaccinated versus unvaccinated patients . RESULTS During 340.4 person-years follow-up , 12 ( 13.6 % ) vaccinated patients and 35 ( 30.7 % ) unvaccinated patients developed recurrent HGAIN . Multivariable hazards ratio ( HR ) analysis showed testing positive for oncogenic HPV genotypes within 8 months before study entry was associated with increased risk of recurrent HGAIN at 2 years after study entry ( HR 4.06 ; 95 % confidence interval [ CI ] , 1.58 - 10.40 ; P = .004 ) , and qHPV was associated with decreased risk of recurrent HGAIN ( HR .50 ; 95 % CI , .26-.98 ; P = .04 ) . Among patients infected with oncogenic HPV , qHPV was associated with decreased risk of recurrent HGAIN at 2 years after study entry ( HR .47 ; 95 % CI , .22 - 1.00 ; P = .05 ) . CONCLUSIONS qHPV significantly reduces HGAIN recurrence  among MSM and may be an effective posttreatment adjuvant form of therapy . A r and omized controlled trial is needed to confirm these results Objective Due to long lag time between infection/cancer diagnoses human papillomavirus ( HPV ) vaccination programs will deliver vaccine efficacy ( VE ) estimates against cancer end-points late . Cancer registry follow-up of population -based , r and omised trial cohorts of vaccinated and unvaccinated women was undertaken for the estimation of VE against cervical intraepithelial neoplasia grade three and invasive cancer ( CIN3 + ) . Methods We report interim results with 98 561 person years of Finnish Cancer Registry -based follow-up of individually and /or cluster r and omised cohorts of HPV-16/18 vaccinated and unvaccinated adolescent women enrolled in June 2003/2005 , and between May 2004 and April 2005 , respectively . The cohorts comprised 15 627 18- to 19-year-old unvaccinated women ( NCT01393470 ) , and 2 401 and 64 16- to 17-year-old HPV-16/18 vaccinated women participating the PATRICIA ( NCT00122681 ) and HPV-012 ( NCT00169494 ) trials , respectively . The age-aligned passive follow-up started 6 months after the clinical trials ’ end . Results During the follow-up of 4.5 to 10 years post enrolment we identified 75 cases of cervical intraepithelial neoplasia grade 3 ( CIN3 ) and 4 cases of invasive cervical cancer ( ICC ) in the unvaccinated cohort , and 4 CIN3 cases in the HPV-16/18 vaccinated women . Diagnostic blocks were available for HPV typing from 87 % of the cases . CIN3 + lesions were detectable in 54 cases . HPV16 was found in 26 of 50 unvaccinated CIN3 + cases , and in 3 CIN3 + cases in the HPV-16/18 vaccinated women . The latter were all baseline positive for cervical HPV16 DNA . Baseline data was not available for the unvaccinated women . Intention-to-treat VE against any CIN3 + was 66 % ( 95 % CI 8 , 88 ) . Conclusions Ten years post vaccination the AS04-adjuvanted HPV-16/18 vaccine shows continued efficacy against CIN3 + irrespectively of HPV type . Vaccine efficacy was not observed in baseline HPV16 DNA positive subjects . Trial registration number NCT01393470 Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more BACKGROUND Infection with human papillomavirus ( HPV ) and diseases caused by HPV are common in boys and men . We report on the safety of a quadrivalent vaccine ( active against HPV types 6 , 11 , 16 , and 18 ) and on its efficacy in preventing the development of external genital lesions and anogenital HPV infection in boys and men . METHODS We enrolled 4065 healthy boys and men 16 to 26 years of age , from 18 countries in a r and omized , placebo-controlled , double-blind trial . The primary efficacy objective was to show that the quadrivalent HPV vaccine reduced the incidence of external genital lesions related to HPV-6 , 11 , 16 , or 18 . Efficacy analyses were conducted in a per- protocol population , in which subjects received all three vaccinations and were negative for relevant HPV types at enrollment , and in an intention-to-treat population , in which subjects received vaccine or placebo , regardless of baseline HPV status . RESULTS In the intention-to-treat population , 36 external genital lesions were seen in the vaccine group as compared with 89 in the placebo group , for an observed efficacy of 60.2 % ( 95 % confidence interval [ CI ] , 40.8 to 73.8 ) ; the efficacy was 65.5 % ( 95 % CI , 45.8 to 78.6 ) for lesions related to HPV-6 , 11 , 16 , or 18 . In the per- protocol population , efficacy against lesions related to HPV-6 , 11 , 16 , or 18 was 90.4 % ( 95 % CI , 69.2 to 98.1 ) . Efficacy with respect to persistent infection with HPV-6 , 11 , 16 , or 18 and detection of related DNA at any time was 47.8 % ( 95 % CI , 36.0 to 57.6 ) and 27.1 % ( 95 % CI , 16.6 to 36.3 ) , respectively , in the intention-to-treat population and 85.6 % ( 97.5 % CI , 73.4 to 92.9 ) and 44.7 % ( 95 % CI , 31.5 to 55.6 ) in the per- protocol population . Injection-site pain was significantly more frequent among subjects receiving quadrivalent HPV vaccine than among those receiving placebo ( 57 % vs. 51 % , P<0.001 ) . CONCLUSIONS Quadrivalent HPV vaccine prevents infection with HPV-6 , 11 , 16 , and 18 and the development of related external genital  lesions in males 16 to 26 years of age . ( Funded by Merck and others ; Clinical Trials.gov number , NCT00090285 . ) Non-r and omised studies of the effects of interventions are critical to many areas of healthcare evaluation , but their results may be biased . It is therefore important to underst and and appraise their strengths and weaknesses . We developed ROBINS-I ( “ Risk Of Bias In Non-r and omised Studies - of Interventions ” ) , a new tool for evaluating risk of bias in estimates of the comparative effectiveness ( harm or benefit ) of interventions from studies that did not use r and omisation  to allocate units ( individuals or clusters of individuals ) to comparison groups . The tool will be particularly useful to those undertaking systematic review s that include non-r and omised studies Background The quadrivalent human papillomavirus vaccine ( qHPV ) is FDA -approved for use in males 9 to 26 years old to prevent anogenital condyloma . The objective of this study is to determine if qHPV is effective at preventing anal condyloma among men who have sex with men ( MSM ) aged 26 years and older . Methods This post-hoc analysis of a nonconcurrent cohort study evaluated 210 patients without history of anal condyloma and 103 patients with previously-treated anal condyloma recurrence-free for at least 12 months prior to vaccination/time zero . We determined the rate of anal condyloma development in vaccinated versus unvaccinated patients . Results 313 patients with mean age 42 years were followed for median 981 days . During 773.6 person-years follow-up , condyloma developed in 10 ( 8.6 % ) vaccinated patients ( incidence of 3.7 per 100 person-years ) and 37 ( 18.8 % ) unvaccinated patients ( incidence 7.3 per 100 person-years ; p = 0.05 ) . Multivariable hazards ratio showed that qHPV was associated with decreased risk of anal condyloma development ( HR 0.45 ; 95 % CI 0.22–0.92 ; p = 0.03 ) . History of anal condyloma was associated with increased risk of anal condyloma development ( HR 2.28 ; 95 % CI 1.28–4.05 ; p = 0.005 ) , as was infection with oncogenic HPV ( HR 3.87 ; 95 % CI 1.66–9.03 ; p = 0.002 ) . Conclusions Among MSM 26 years of age and older with and without history of anal condyloma , qHPV reduces the risk of anal condyloma development . A r and omized controlled trial is needed to confirm these findings in this age group INTRODUCTION Human papillomavirus ( HPV ) is one of the most common sexually transmitted infections and is the cause of several different diseases in men and women . Although little is known about HPV infection in men , they are also in the risk group of HPV infection and play an important role in transmitting the virus to women . AIM To define the efficacy of the HPV vaccine through cross-immunization and its role in clearance of HPV infection , and to assess infection-associated factors in men . METHODS This prospect i ve r and omized clinical study enrolled 171 evaluable men with genital warts between June 2009 and October 2013 . After the initial treatment intervention , 91 patients were r and omly assigned to receive HPV vaccine in three doses . Eighty patients were in the  control  ( unvaccinated ) group . One hundred-eleven men were single and 60 men were married . Patients who had previous treatment for pre-existing warts and medical disorders that needed chronic treatment or immunosuppression were not included in the r and omization . Also 29 men with follow-up less than 12 months and incomplete vaccination were not included . MAIN OUTCOME MEASURES The patients were assessed regarding age , condom use , marital status , number of visible genital warts , and smoking status . Post-treatment follow-up was monthly up to 12th month . RESULTS Mean age was 34 ± 7.6 . One hundred fifteen patients were smokers . For the recurrence of warts , age , smoking , vaccination status were insignificant and marital status was significant in the univariable analysis ; only marital status preserved significance ( HR : 2.0 CI:1.29 - 3.12 P = 0.002 ) in the multivariable analysis including vaccination status , marital status , and smoking . CONCLUSION Among the investigated factors vaccination status was not but marital status significantly influenced wart recurrence . Married men had more recurrences in our population . Larger multicenter r and omized clinical trials are lacking and seriously required to investigate the therapeutic effect of current quadrivalent HPV vaccine in genital warts BACKGROUND The rate of anal cancer is increasing among both women and men , particularly men who have sex with men . Caused by infection with human papillomavirus ( HPV ) , primarily HPV type 16 or 18 , anal cancer is preceded by high- grade anal intraepithelial neoplasia ( grade 2 or 3 ) . We studied the safety and efficacy of quadrivalent HPV vaccine ( qHPV ) against anal intraepithelial neoplasia associated with HPV-6 , 11 , 16 , or 18 infection in men who have sex with men . METHODS In a sub study of a larger double-blind study , we r and omly assigned 602 healthy men who have sex with men , 16 to 26 years of age , to receive either qHPV or placebo . The primary efficacy objective was prevention of anal intraepith 
    Output:
    