Systematic literature review of cross-protective effect of HPV vaccines based on data from randomized clinical trials and real-world evidence |
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Affiliation: | 1. Medicine, Indiana University School of Medicine, Indianapolis, IN, USA;2. Gynecologic Oncology, Medical University Vienna, Vienna, Austria;3. Center for Observational and Real-World Evidence, Merck & Co., Inc., Kenilworth, NJ, USA;4. Late Stage Development Vaccines, Merck & Co., Inc., Kenilworth, NJ, USA;5. Global Center for Scientific Affairs, Merck & Co., Inc., Kenilworth, NJ, USA;6. Global Vaccines Medical Affairs, Merck & Co., Inc., Kenilworth, NJ, USA;7. Universidad del Rosario, Bogota, Colombia;8. Certara Evidence and Access, Montreal, Quebec, Canada;9. Pathology, University of Cambridge, Cambridge, United Kingdom |
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Abstract: | BackgroundThe extent of cross-protection provided by currently licensed bivalent and quadrivalent HPV vaccines versus direct protection against HPV 31-, 33-, 45-, 52-, and 58-related disease is debated. A systematic literature review was conducted to establish the duration and magnitude of cross-protection in interventional and observational studies.MethodsPubMed and Embase databases were searched to identify randomized controlled trials (RCT) and observational studies published between 2008 and 2019 reporting on efficacy and effectiveness of HPV vaccines in women against non-vaccine types 31, 33, 45, 52, 58, and 6 and 11 (non-bivalent types). Key outcomes of interest were vaccine efficacy against 6- and 12-month persistent infection or genital lesions, and type-specific genital HPV prevalence or incidence. RCT data were analyzed for the according-to-protocol (bivalent vaccine) or negative-for-14-HPV-types (quadrivalent vaccine) efficacy cohorts.ResultsData from 23 RCTs and 33 observational studies evaluating cross-protection were extracted. RCTs assessed cross-protection in post-hoc analyses of small size subgroups. Among fully vaccinated, baseline HPV-naïve women, the bivalent vaccine showed statistically significant cross-protective efficacy, although with wide confidence intervals, against 6-month and 12-month persistent cervical infections and CIN2+ only consistently for HPV 31 and 45, with the highest effect observed for HPV 31 (range 64.6% [95% CI: 27.6 to 83.9] to 79.1% [97.7% CI: 27.6 to 95.9] for 6-month persistent infection; maximal follow-up 4.7 years). No cross-protection was shown in extended follow-up. The quadrivalent vaccine efficacy reached statistical significance for HPV 31 (46.2% [15.3–66.4]; follow-up: 3.6 years). Similarly, observational studies found consistently significant effectiveness only against HPV 31 and 45 with both vaccines.ConclusionsRCTs and observational studies show that cross-protection is inconsistent across non-vaccine HPV types and is largely driven by HPV 31 and 45. Furthermore, existing data suggest that it wanes over time; its long-term durability has not been established. |
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Keywords: | Human papillomavirus Vaccine Cross-protection Bivalent Quadrivalent AIN" },{" #name" :" keyword" ," $" :{" id" :" k0035" }," $$" :[{" #name" :" text" ," _" :" anal intraepithelial neoplasia AIS" },{" #name" :" keyword" ," $" :{" id" :" k0045" }," $$" :[{" #name" :" text" ," _" :" adenocarcinoma in situ ASCUS" },{" #name" :" keyword" ," $" :{" id" :" k0055" }," $$" :[{" #name" :" text" ," _" :" atypical squamous cells of undetermined significance ATP-E" },{" #name" :" keyword" ," $" :{" id" :" k0065" }," $$" :[{" #name" :" text" ," _" :" according-to-protocol efficacy CIN" },{" #name" :" keyword" ," $" :{" id" :" k0075" }," $$" :[{" #name" :" text" ," _" :" cervical intraepithelial neoplasia CVT" },{" #name" :" keyword" ," $" :{" id" :" k0085" }," $$" :[{" #name" :" text" ," _" :" Costa Rica Vaccine Trial FUTURE" },{" #name" :" keyword" ," $" :{" id" :" k0095" }," $$" :[{" #name" :" text" ," _" :" Females United to Unilaterally Reduce Endo/Ectocervical Disease HAVANA" },{" #name" :" keyword" ," $" :{" id" :" k0105" }," $$" :[{" #name" :" text" ," _" :" HPV Amongst Vaccinated and Non-vaccinated Adolescents HIV" },{" #name" :" keyword" ," $" :{" id" :" k0115" }," $$" :[{" #name" :" text" ," _" :" human immunodeficiency virus HPV" },{" #name" :" keyword" ," $" :{" id" :" k0125" }," $$" :[{" #name" :" text" ," _" :" human papillomavirus HSIL" },{" #name" :" keyword" ," $" :{" id" :" k0135" }," $$" :[{" #name" :" text" ," _" :" high-grade intraepithelial lesion ITT" },{" #name" :" keyword" ," $" :{" id" :" k0145" }," $$" :[{" #name" :" text" ," _" :" intention-to-treat LSIL" },{" #name" :" keyword" ," $" :{" id" :" k0155" }," $$" :[{" #name" :" text" ," _" :" low-grade squamous intraepithelial lesion mo" },{" #name" :" keyword" ," $" :{" id" :" k0165" }," $$" :[{" #name" :" text" ," _" :" months Natsal" },{" #name" :" keyword" ," $" :{" id" :" k0175" }," $$" :[{" #name" :" text" ," _" :" National Surveys of Sexual Attitudes and Lifestyles PASSYON" },{" #name" :" keyword" ," $" :{" id" :" k0185" }," $$" :[{" #name" :" text" ," _" :" PApillomavirus Surveillance among STI clinic YOungsters in the Netherlands PATRICIA" },{" #name" :" keyword" ," $" :{" id" :" k0195" }," $$" :[{" #name" :" text" ," _" :" PApilloma TRIal against Cancer In young Adults RCT" },{" #name" :" keyword" ," $" :{" id" :" k0205" }," $$" :[{" #name" :" text" ," _" :" randomized clinical trial RWE" },{" #name" :" keyword" ," $" :{" id" :" k0215" }," $$" :[{" #name" :" text" ," _" :" real-world evidence SLR" },{" #name" :" keyword" ," $" :{" id" :" k0225" }," $$" :[{" #name" :" text" ," _" :" systematic literature review TVC" },{" #name" :" keyword" ," $" :{" id" :" k0235" }," $$" :[{" #name" :" text" ," _" :" total vaccinated cohort UK" },{" #name" :" keyword" ," $" :{" id" :" k0245" }," $$" :[{" #name" :" text" ," _" :" United Kingdom US" },{" #name" :" keyword" ," $" :{" id" :" k0255" }," $$" :[{" #name" :" text" ," _" :" United States USA" },{" #name" :" keyword" ," $" :{" id" :" k0265" }," $$" :[{" #name" :" text" ," _" :" United States of America VACCINE" },{" #name" :" keyword" ," $" :{" id" :" k0275" }," $$" :[{" #name" :" text" ," _" :" Vaccine Against Cervical Cancer Impact and Effectiveness VaIN" },{" #name" :" keyword" ," $" :{" id" :" k0285" }," $$" :[{" #name" :" text" ," _" :" vaginal intraepithelial neoplasia VIN" },{" #name" :" keyword" ," $" :{" id" :" k0295" }," $$" :[{" #name" :" text" ," _" :" vulvar intraepithelial neoplasia VIVIANE" },{" #name" :" keyword" ," $" :{" id" :" k0305" }," $$" :[{" #name" :" text" ," _" :" Human PapillomaVIrus Vaccine Immunogenicity ANd Efficacy VLP" },{" #name" :" keyword" ," $" :{" id" :" k0315" }," $$" :[{" #name" :" text" ," _" :" virus-like particle yr" },{" #name" :" keyword" ," $" :{" id" :" k0325" }," $$" :[{" #name" :" text" ," _" :" years |
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