Daniel C Beachler1, Aimée R Kreimer2, Mark Schiffman2, Rolando Herrero2, Sholom Wacholder2, Ana Cecilia Rodriguez2, Douglas R Lowy2, Carolina Porras2, John T Schiller2, Wim Quint2, Silvia Jimenez2, Mahboobeh Safaeian2, Linda Struijk2, John Schussler2, Allan Hildesheim2, Paula Gonzalez2. 1. Division of Cancer Epidemiology, and Genetics (DCB, ARK, MS, SW, MS, AH) and Center for Cancer Research (DRL, JTS), National Cancer Institute, NIH, Bethesda, MD; Proyecto Epidemiológico Guanacaste, Fundación INCIENSA, Costa Rica (RH, ACR, CP, SJ, PG); Early Detection and Prevention Section, International Agency for Research on Cancer, Lyon, France (RH); DDL Diagnostic Laboratory, Voorburg, the Netherlands (WQ, LS); Information Management Systems, Rockville, MD (JS). daniel.beachler@nih.gov. 2. Division of Cancer Epidemiology, and Genetics (DCB, ARK, MS, SW, MS, AH) and Center for Cancer Research (DRL, JTS), National Cancer Institute, NIH, Bethesda, MD; Proyecto Epidemiológico Guanacaste, Fundación INCIENSA, Costa Rica (RH, ACR, CP, SJ, PG); Early Detection and Prevention Section, International Agency for Research on Cancer, Lyon, France (RH); DDL Diagnostic Laboratory, Voorburg, the Netherlands (WQ, LS); Information Management Systems, Rockville, MD (JS).
Abstract
BACKGROUND: Previous Costa Rica Vaccine Trial (CVT) reports separately demonstrated vaccine efficacy against HPV16 and HPV18 (HPV16/18) infections at the cervical, anal, and oral regions; however, the combined overall multisite efficacy (protection at all three sites) and vaccine efficacy among women infected with HPV16 or HPV18 prior to vaccination are less known. METHODS:Women age 18 to 25 years from the CVT were randomly assigned to the HPV16/18 vaccine (Cervarix) or a hepatitis A vaccine. Cervical, oral, and anal specimens were collected at the four-year follow-up visit from 4186 women. Multisite and single-site vaccine efficacies (VEs) and 95% confidence intervals (CIs) were computed for one-time detection of point prevalent HPV16/18 in the cervical, anal, and oral regions four years after vaccination. All statistical tests were two-sided. RESULTS: The multisite woman-level vaccine efficacy was highest among "naïve" women (HPV16/18 seronegative and cervical HPV high-risk DNA negative at vaccination) (vaccine efficacy = 83.5%, 95% CI = 72.1% to 90.8%). Multisite woman-level vaccine efficacy was also demonstrated among women with evidence of a pre-enrollment HPV16 or HPV18 infection (seropositive for HPV16 and/or HPV18 but cervical HPV16/18 DNA negative at vaccination) (vaccine efficacy = 57.8%, 95% CI = 34.4% to 73.4%), but not in those with cervical HPV16 and/or HPV18 DNA at vaccination (anal/oral HPV16/18 VE = 25.3%, 95% CI = -40.4% to 61.1%). Concordant HPV16/18 infections at two or three sites were also less common in HPV16/18-infected women in the HPV vaccine vs control arm (7.4% vs 30.4%, P < .001). CONCLUSIONS: This study found high multisite vaccine efficacy among "naïve" women and also suggests the vaccine may provide protection against HPV16/18 infections at one or more anatomic sites among some women infected with these types prior to HPV16/18 vaccination. Published by Oxford University Press 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.
RCT Entities:
BACKGROUND: Previous Costa Rica Vaccine Trial (CVT) reports separately demonstrated vaccine efficacy against HPV16 and HPV18 (HPV16/18) infections at the cervical, anal, and oral regions; however, the combined overall multisite efficacy (protection at all three sites) and vaccine efficacy among women infected with HPV16 or HPV18 prior to vaccination are less known. METHODS:Women age 18 to 25 years from the CVT were randomly assigned to the HPV16/18 vaccine (Cervarix) or a hepatitis A vaccine. Cervical, oral, and anal specimens were collected at the four-year follow-up visit from 4186 women. Multisite and single-site vaccine efficacies (VEs) and 95% confidence intervals (CIs) were computed for one-time detection of point prevalent HPV16/18 in the cervical, anal, and oral regions four years after vaccination. All statistical tests were two-sided. RESULTS: The multisite woman-level vaccine efficacy was highest among "naïve" women (HPV16/18 seronegative and cervical HPV high-risk DNA negative at vaccination) (vaccine efficacy = 83.5%, 95% CI = 72.1% to 90.8%). Multisite woman-level vaccine efficacy was also demonstrated among women with evidence of a pre-enrollment HPV16 or HPV18 infection (seropositive for HPV16 and/or HPV18 but cervical HPV16/18 DNA negative at vaccination) (vaccine efficacy = 57.8%, 95% CI = 34.4% to 73.4%), but not in those with cervical HPV16 and/or HPV18 DNA at vaccination (anal/oral HPV16/18 VE = 25.3%, 95% CI = -40.4% to 61.1%). Concordant HPV16/18 infections at two or three sites were also less common in HPV16/18-infected women in the HPV vaccine vs control arm (7.4% vs 30.4%, P < .001). CONCLUSIONS: This study found high multisite vaccine efficacy among "naïve" women and also suggests the vaccine may provide protection against HPV16/18 infections at one or more anatomic sites among some women infected with these types prior to HPV16/18 vaccination. Published by Oxford University Press 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.
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