A 9-valent HPV vaccine against infection and intraepithelial neoplasia in women. Immunologic responses following administration of a vaccine targeting human papillomavirus Types 6, 11, 16, and 18. Sustained efficacy, immunogenicity, and safety of the HPV-16/18 AS04-adjuvanted vaccine Design of a large outcome trial for a multivalent human papillomavirus L1 virus-like particle vaccine. Safety and immunogenicity of a 9-valent HPV vaccine in females 12-26 years of age who previously received the quadrivalent HPV vaccine. High-risk human papillomavirus genotypes distribution in a cohort of HIV-positive women living in Europe: epidemiological implication for vaccination against human papillomavirus A seamless Phase IIB/III adaptive outcome trial: Design rationale and implementation challenges Phase II studies to select the formulation of a multivalent HPV L1 virus-like particle (VLP) vaccine A phase III clinical study to compare the immunogenicity and safety of the 9-valent and quadrivalent HPV vaccines in men. Statistical considerations. Potential cost-effectiveness of the nonavalent human papillomavirus (HPV) vaccine. An Open-Label, Randomized Study of a 9-Valent Human Papillomavirus Vaccine Given Concomitantly with Diphtheria, Tetanus, Pertussis and Poliomyelitis Vaccines to Healthy Adolescents 11–15 Years of Age Phase III, randomized controlled trial in girls 9-15 years old to evaluate lot consistency of a novel nine-valent human papillomavirus L1 virus-like particle vaccine
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 % carried OHR without HPV 16 or 18 and 11 % had concomitant infection by OHR and HPV 16 or 18 . The most frequent HRHPV were HPV52 ( 19.8 % ) , HPV18 ( 14.6 % ) , HPV31/35/51/58 ( 12.1 % each ) , HPV56 ( 9.9 % ) and HPV16 ( 9.5 % ) . Less than 30 % of women had their HRHPV genotypes included in the bivalent or quadrivalent vaccines against HRHPV 16 and 18 ; however , 79 % had their HRHPV covered by the ninevalent vaccine against HRHPV 16/18/31/33/45/52/58 . Conclusion : The HRHPV genotypes distribution found in these women living in Europe with a successfully treated HIV is similar to the one found in Central Africa with HRHPV other than HPV16 or 18 retrieved in 87 % . In this population , the bivalent or quadrivalent vaccines could offer protection in only 30 % of women ; however this protection could be extended up to 80 % with the ninevalent vaccine Background : The licensed four-valent prophylactic human papillomavirus vaccine is highly efficacious in preventing cervical , vulvar , vaginal , and anal cancers and related precancers caused by human papillomavirus types 6 , 11 , 16 , and 18 . These four types account for approximately 70 % of cervical cancers . A nine-valent human papillomavirus vaccine , including the four original types ( 6 , 11 , 16 , and 18 ) plus the next five most prevalent types in cervical cancer ( 31 , 33 , 45 , 52 , and 58 ) could provide approximately 90 % overall cervical cancer coverage . To expedite the nine-valent human papillomavirus vaccine clinical development , an adaptive , seamless Phase IIB/III outcome trial with ∼15,000 subjects was conducted to facilitate dose formulation selection and provide pivotal evidence of safety and efficacy for regulatory registration s. Purpose : We discuss the design rationale and implementation challenges of the outcome trial , focusing on the adaptive feature of the seamless Phase IIB/III design . Methods : Subjects were enrolled in two parts ( Part A and Part B ) . Approximately 1240 women , 16–26 years of age , were enrolled in Part A for Phase IIB evaluation and equally r and omized to one of three dose formulations of the nine-valent human papillomavirus vaccine or the four-valent human papillomavirus vaccine ( active control ) . Based on an interim analysis of immunogenicity and safety , one dose formulation of the nine-valent human papillomavirus vaccine was selected for evaluation in the Phase III part of the study . Subjects enrolled in Part A who received the selected dose formulation of the nine-valent human papillomavirus vaccine or four-valent human papillomavirus vaccine continued to be followed up and contributed to the final efficacy and safety analyses . In addition , ∼13,400 women 16–26 years of age were enrolled in Part B , r and omized to nine-valent human papillomavirus vaccine at the selected dose formulation or four-valent human papillomavirus vaccine , and followed for immunogenicity , efficacy , and safety . Results : A seamless Phase IIB/III design was justified by the extensive pre-existing knowledge of the licensed four-valent human papillomavirus vaccine and the development objectives for the nine-valent human papillomavirus vaccine . Subjects enrolled in Part A who received either the selected nine-valent human papillomavirus formulation or four-valent human papillomavirus vaccine contributed ∼10 % of person-years of follow-up due to its earlier start — thereby maximizing the overall efficiency of the trial . Some of the challenges encountered in the implementation of the adaptive design included practical considerations during Phase IIB formulation selection by internal and external committees , End-of-Phase II discussion with health authorities and managing changes in the assay for immunological endpoints . Limitations : Application of the experience and lesson learned from this seamless adaptive design to other clinical programs may depend on case-by-case consideration . Conclusion : A seamless Phase IIB/III adaptive design was successfully implemented in this large outcome study . The development time of the second-generation nine-valent human papillomavirus vaccine was shortened due to improved statistical efficiency Our objective was to develop a multivalent prophylactic HPV vaccine that protects against infection and disease caused by HPV16/18 ( oncogenic types in existing prophylactic vaccines ) plus additional oncogenic types by conducting 3 Phase II studies comparing the immunogenicity ( i.e. , anti-HPV6/11/16/18 geometric mean titers [ GMT ] ) and safety of 7 vaccine c and i date s with the licensed quadrivalent HPV6/11/16/18 vaccine ( qHPV vaccine ) in young women ages 16–26 . In the first study ( Study 1 ) , subjects received one of 3 dose formulations of an 8-valent HPV6/11/16/18/31/45/52/58 vaccine or qHPV vaccine ( control ) . In Study 2 , subjects received one of 3 dose formulations ( termed low- , mid- , and high-dose formulations , respectively ) of a 9-valent HPV6/11/16/18/31/33/45/52/58 vaccine ( 9vHPV vaccine ) or qHPV vaccine ( control ) . In Study 3 , subjects concomitantly received qHPV vaccine plus 5-valent HPV31/33/45/52/58 or qHPV vaccine plus placebo ( control ) . All vaccines were administered at day 1/month 2/month 6 . In studies 1 and 3 , anti-HPV6/11/16/18 GMTs at month 7 were non-inferior in the experimental arms compared with the control arm ; however , there was a trend for lower antibody responses for all 4 HPV types . In Study 2 , this immune interference was overcome with the mid- and high-dose formulations of the 9vHPV vaccine by increasing antigen and adjuvant doses . In all 3 studies , all vaccine c and i date s were strongly immunogenic with respect to HPV31/33/45/52/58 and were well tolerated . Based on the totality of the results , the middle dose formulation of the 9vHPV vaccine was selected for Phase III evaluation . Each 0.5mL dose contains 30μg/40μg/60μg/40μg/20μg/20μg/20μg/20μg/20μg of HPV6/11/16/18/31/33/45/52/58 virus-like particles , and 500μg of amorphous aluminum hydroxyphosphate sulfate adjuvant . Clinical Trials.gov numbers NCT00260039 , NCT00543543 , and NCT00551187 BACKGROUND A nine-valent human papilloma virus ( 9vHPV ) vaccine has been developed to prevent infections and diseases related to HPV 6/11/16/18 ( as per the licensed quadrivalent HPV ( qHPV ) vaccine ) as well as to five additional oncogenic HPV types ( HPV 31/33/45/52/58 ) . The 9vHPV vaccine has the potential to prevent 90 % of cervical cancers , HPV-related anal , vaginal and vulval cancers and anogenital warts . We compared the immunogenicity and safety of the 9vHPV vaccine versus the qHPV vaccine in 16 - 26-year-old men . METHODS Participants ( N=500 ) were r and omised to receive 9vHPV or qHPV vaccines on day 1 , month 2 and month 6 . Serology testing was performed on day 1 and month 7 . HPV type-specific antibody titres ( anti-HPV 6/11/16/18/31/33/45/52/58 ) were determined by competitive Luminex immunoassay and expressed as geometric mean titres and seroconversion rates . Vaccine safety was also assessed . RESULTS The HPV 6/11/16/18 immune responses elicited by the 9vHPV vaccine were comparable with those elicited by the qHPV vaccine . All participants receiving the 9vHPV vaccine seroconverted for HPV 31/33/45/52/58 . The 9vHPV and qHPV vaccines showed comparable safety profiles . CONCLUSIONS In addition to immune responses to HPV 31/33/45/52/58 , a three-dose regimen of the 9vHPV vaccine elicited a similar immune response to HPV 6/11/16/18 when compared with the qHPV vaccine in men aged 16 - 26years . The safety profile was also similar for the two vaccines . The results from this study support extending the efficacy findings with qHPV vaccine to 9vHPV vaccine in men aged 16 - 26years . NCT02114385 The main goal of the study is to determine the benefit of higher dosage of indomethacin ( HDI ) compared with stopping treatment after the lower dosage ( SDI ) . The cascaded nature of the study , whereby patients only move to the higher dosing regimen if st and ard dosing does not close the PDA , complicates the analysis . The suggestion of potential selection bias is confirmed when we consider Table 1 in themanuscript where those onHDI have slightly lower gestational age ( 27.4 vs. 26.2 , p1⁄40.01 ) and birthweight ( 950 vs. 833 g , p1⁄40.05 ) . The overlapping group structure , SD vs. SDþHDI , leads to dependencies and therefore increased correlation that should also be considered in the analysis . We performed a supplementary analysis to estimate the potential effect of selection bias on the analysis results by using propensity scores to create a case control setting . The 52 patients receiving HDI were considered as the treatment group , and the control group donor pool was defined to be those patients receiving st and ard dosing , excluding those patients that subsequently move to the HDI group ( i.e. , 248–521⁄4196 patients ) . Wefitted a logisticmodelwith dependent variable the indicator of treatment ( SDI1⁄40 , HDI1⁄41 ) , and independent variables gender , birthweight and gestational age , to derive the score . We employed nearest neighbor 1:1matching using the “ MatchIt ” package in R to find similar patients to those in the HDI group . Figure S1 shows the propensity scores of those matched compared with those unmatched ; we can determine a good match between those paired in terms of their propensity score . Following matching , in the control group ( SDI only ) there were 42/52 primary PDA closures compared with 32/52 in the HDI group ( 81 vs. 62 % , p1⁄40.05 ) . This supplementary analysis indicates a marginal trend toward the number of primary PDA closures being slightly higher in the st and ard dosing group compared with those receiving higher dosing ; there had been r and om allocation of patients to each of the arms . Although this trend is marginally significant , it does not conclusively contradict the conclusion of no difference between the closure rates stated in the text of the article ( section “ secondary outcome : efficacy of treatment ” ( 65.3 vs. 65.4 % , p1⁄40.9 ) . Supplementary R and omized clinical trials are currently examining the efficacy of a nonavalent human papillomavirus ( HPV ) vaccine , including HPV-types 6/11/16/18/31/33/45/52/58 . Evidence on the cost-effectiveness of the nonavalent is required for timely policy-decisions . We compared the potential cost-effectiveness of the nonavalent and quadrivalent HPV vaccines . We used a multi-type individual-based transmission-dynamic model of HPV infection and diseases , 70-year time-horizon , 3 % discount rate and healthcare payer perspective . We calibrated the model to Canadian sexual behavior and epidemiologic data , and estimated Quality -Adjusted Life-Years ( QALYs ) lost and costs ( $ CAN 2010 ) from the literature . Under base-case assumptions ( vaccinating 10-year-old girls , 80 % coverage , 95$/dose , vaccine-type efficacy = 95 % , cross-protection for the quadrivalent vaccine , duration of vaccine-type protection ( cross-protection ) = 20 ( 10 ) years ) , using the quadrivalent and nonavalent vaccines is estimated to cost $ 15,528 [ 12,056 ; 19,140 ] and $ 12,203 [ 9,331 ; 17,292 ] per QALY-gained , respectively . At equal price , the nonavalent vaccine is more cost-effective than the quadrivalent vaccine , even when assuming both shorter duration of protection ( nonavalent = 20 years vs. quadrivalent = lifelong ) and lower vaccine-type efficacy ( nonavalent = 85 % vs. quadrivalent = 95 % ) . However , the additional cost per dose of the nonavalent vaccine should not exceed $ 11 to remain more cost-effective than the quadrivalent vaccine , and $ 24 to represent a cost-effective alternative to the quadrivalent vaccine ( using a $ 40,000/QALY-gained threshold ) . The nonavalent vaccine can be a cost-effective alternative to the quadrivalent vaccine , even in scenarios where nonavalent vaccine efficacy is 85 % . However , because most cervical cancers are caused by HPV-16/18 , it is unlikely that the nonavalent would be used if its efficacy against these types is lower than current HPV vaccines Background : A 9-valent human papillomavirus ( 9vHPV ) vaccine has recently been reported to be safe and highly efficacious against infection and disease related to HPV6/11/16/18/31/33/45/52/58 . We evaluated the immunogenicity and safety of the 9vHPV vaccine administered concomitantly with REPEVAX ( diphtheria , tetanus , acellular pertussis and inactivated poliomyelitis vaccine ) . Methods : This open-label , r and omized , multicenter study enrolled 1054 males and females ages 11–15 years . Subjects were r and omly assigned to each group in a 1:1 ratio . Subjects received a 0.5 mL dose of 9vHPV vaccine intramuscularly at day 1 , months 2 and 6 and a 0.5 mL dose of REPEVAX either on day 1 ( concomitant vaccination group ; n = 526 ) or at month 1 ( nonconcomitant vaccination group , n = 528 ) . Serologic responses for each vaccine component were tested by 1-sided tests of noninferiority between groups . Systemic and injection-site adverse experiences ( AEs ) and serious AEs were monitored . Results : Noninferiority of anti-HPV geometric mean titers and seroconversion rates for all 9vHPV antigens were demonstrated for the concomitant group compared with the nonconcomitant group . Seroconversion rates for the 9vHPV vaccine types were ≥99.8 % in both groups at month 7 . For REPEVAX  , noninferiority of immune response was established for diphtheria , tetanus , all polio and pertussis antigens for both groups . There were no vaccine-related serious AEs . Conclusion : Overall , concomitant administration of 9vHPV vaccine and REPEVAX was generally well tolerated and did not interfere with the immune response to either vaccine . This strategy would minimize the number of visits required to deliver each vaccine individually A 9-valent human papillomavirus ( 6/11/16/18/31/33/45/52/58 ) VLP ( 9vHPV ) vaccine has recently been proven highly efficacious in preventing disease associated with vaccine HPV types in a pivotal Phase III study . The demonstration of lot-to-lot consistency to confirm the reliability of the manufacturing process is a regulatory requirement for vaccine licensure in the United States . A r and omized trial was conducted to demonstrate that three lots of 9vHPV vaccine elicit equivalent antibody response for all 9 vaccine types . The study required thorough planning because it required success on 27 separate statistical comparisons . An innovative statistical approach was used taking into account between-lot variance for more conservative power calculations . The study demonstrated equivalence of three lots of 9vHPV vaccine for all 9 vaccine types
In 2014 , the Food and Drug Administration approved a new human papillomavirus 9-valent vaccine ( 9vHPV ) , targeting nine HPV types : HPV types 6 , 11 , 16 , and 18 , which are also targeted by the quadrivalent HPV vaccine ( qHPV ) , plus five additional high cancer risk HPV types ( HPV types 31 , 33 , 45 , 52 , and 58 ) .
The aim of the current study was to systematic ally retrieve , qualitatively and quantitatively pool , as well as critically appraise all available evidence on 9vHPV from r and omized controlled trials ( RCTs ) .