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Clinical Trial
. 2014 Aug 15;210(4):517-34.
doi: 10.1093/infdis/jiu139. Epub 2014 Mar 8.

Risk of newly detected infections and cervical abnormalities in women seropositive for naturally acquired human papillomavirus type 16/18 antibodies: analysis of the control arm of PATRICIA

Xavier Castellsagué  1 , Paulo Naud  2 , Song-Nan Chow  3 , Cosette M Wheeler  4 , Maria Julieta V Germar  5 , Matti Lehtinen  6 , Jorma Paavonen  7 , Unnop Jaisamrarn  8 , Suzanne M Garland  9 , Jorge Salmerón  10 , Dan Apter  11 , Henry Kitchener  12 , Julio C Teixeira  13 , S Rachel Skinner  14 , Genara Limson  15 , Anne Szarewski  16 , Barbara Romanowski  17 , Fred Y Aoki  18 , Tino F Schwarz  19 , Willy A J Poppe  20 , F Xavier Bosch  21 , Newton S de Carvalho  22 , Klaus Peters  23 , Wiebren A A Tjalma  24 , Mahboobeh Safaeian  25 , Alice Raillard  26 , Dominique Descamps  27 , Frank Struyf  27 , Gary Dubin  28 , Dominique Rosillon  27 , Laurence Baril  27
Affiliations
Clinical Trial

Risk of newly detected infections and cervical abnormalities in women seropositive for naturally acquired human papillomavirus type 16/18 antibodies: analysis of the control arm of PATRICIA

Xavier Castellsagué et al. J Infect Dis. .

Abstract

Background: We examined risk of newly detected human papillomavirus (HPV) infection and cervical abnormalities in relation to HPV type 16/18 antibody levels at enrollment in PATRICIA (Papilloma Trial Against Cancer in Young Adults; NCT00122681).

Methods: Using Poisson regression, we compared risk of newly detected infection and cervical abnormalities associated with HPV-16/18 between seronegative vs seropositive women (15-25 years) in the control arm (DNA negative at baseline for the corresponding HPV type [HPV-16: n = 8193; HPV-18: n = 8463]).

Results: High titers of naturally acquired HPV-16 antibodies and/or linear trend for increasing antibody levels were significantly associated with lower risk of incident and persistent infection, atypical squamous cells of undetermined significance or greater (ASCUS+), and cervical intraepithelial neoplasia grades 1/2 or greater (CIN1+, CIN2+). For HPV-18, although seropositivity was associated with lower risk of ASCUS+ and CIN1+, no association between naturally acquired antibodies and infection was demonstrated. Naturally acquired HPV-16 antibody levels of 371 (95% confidence interval [CI], 242-794), 204 (95% CI, 129-480), and 480 (95% CI, 250-5756) EU/mL were associated with 90% reduction of incident infection, 6-month persistent infection, and ASCUS+, respectively.

Conclusions: Naturally acquired antibodies to HPV-16, and to a lesser extent HPV-18, are associated with some reduced risk of subsequent infection and cervical abnormalities associated with the same HPV type.

Keywords: HPV; cervical abnormality; infection; naturally acquired antibodies; risk reduction.

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Figures

Figure 1.
Figure 1.
Participant disposition. Abbreviations: ASCUS, atypical squamous cells of undetermined significance; CIN, cervical intraepithelial neoplasia; HPV, human papillomavirus; MO, Month 0; TVC-E, total vaccinated cohort for efficacy.
Figure 2.
Figure 2.
Cumulative probability of detecting an incident or 6-month persistent infection or developing atypical squamous cells of undetermined significance or greater (ASCUS+) associated with human papillomavirus type 16 (HPV-16). A, Incident HPV-16 infection. B, HPV-16 six-month persistent infection. C, ASCUS+ associated with HPV-16.
Figure 2.
Figure 2.
Cumulative probability of detecting an incident or 6-month persistent infection or developing atypical squamous cells of undetermined significance or greater (ASCUS+) associated with human papillomavirus type 16 (HPV-16). A, Incident HPV-16 infection. B, HPV-16 six-month persistent infection. C, ASCUS+ associated with HPV-16.
Figure 3.
Figure 3.
Cumulative probability of detecting an incident or 6-month persistent infection or developing atypical squamous cells of undetermined significance or greater (ASCUS+) associated with human papillomavirus type 18 (HPV-18). A, Incident HPV-18 infection. B, HPV-18 six-month persistent infection. C, ASCUS+ associated with HPV-18.
Figure 3.
Figure 3.
Cumulative probability of detecting an incident or 6-month persistent infection or developing atypical squamous cells of undetermined significance or greater (ASCUS+) associated with human papillomavirus type 18 (HPV-18). A, Incident HPV-18 infection. B, HPV-18 six-month persistent infection. C, ASCUS+ associated with HPV-18.
Figure 4.
Figure 4.
Relationship between initial antibody level and 6-month persistent infection or atypical squamous cells of undetermined significance or greater (ASCUS+) associated with human papillomavirus type 16. A, 6-month persistent infection. B, ASCUS+. The dot size is proportional to the number of subjects, the gray dot represents all seronegative subjects, and red dots represent approximately 5-percentile classes of seropositive subjects. The solid blue line corresponds to the Poisson regression model (the dotted lines are 95% confidence limits). The dotted red lines correspond to a 50%, 70%, and 90% reduction of the incidence of the endpoint (6-month persistent infection or ASCUS+), and the values in red are the corresponding threshold values of antibody titer. Sensitivity analyses including the covariates of age at first sexual intercourse and smoking history, or including only a subset of 100 seronegative subjects, produced similar results. For example, including the covariates of age at first sexual intercourse and smoking history for all seronegative subjects, the estimated antibody titers (with 95% confidence interval) yielding 90%, 70%, and 50% reductions in 6-month persistent infection were 180 (118–377), 94 (62–197), and 54 (36–114) EU/mL, respectively. Abbreviations: CI, confidence interval; ELISA, enzyme-linked immunosorbent assay; HPV-16, human papillomavirus type 16.
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References

    1. de Sanjosé S, Quint WGV, Alemany L, et al. Human papillomavirus genotype attribution in invasive cervical cancer: a retrospective cross-sectional survey. Lancet Oncol. 2010;11:1048–56. - PubMed
    1. The GlaxoSmithKline Vaccine HPV-007 Study Group. Sustained efficacy and immunogenicity of the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine: analysis of a randomised placebo-controlled trial up to 6.4 years. Lancet. 2009;374:1975–85. - PubMed
    1. Paavonen J, Naud P, Salmerón J, et al. Efficacy of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine against cervical infection and precancer caused by oncogenic HPV types (PATRICIA): final analysis of a double-blind, randomised study in young women. Lancet. 2009;374:301–14. - PubMed
    1. Garland SM, Hernandez-Avila M, Wheeler CM, et al. Quadrivalent vaccine against human papillomavirus to prevent anogenital diseases. N Engl J Med. 2007;356:1928–43. - PubMed
    1. The FUTURE II Study Group. Quadrivalent vaccine against human papillomavirus to prevent high-grade cervical lesions. N Engl J Med. 2007;356:1916–27. - PubMed

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