Risk of HPV-16/18 Infections and Associated Cervical Abnormalities in Women Seropositive for Naturally Acquired Antibodies: Pooled Analysis Based on Control Arms of Two Large Clinical Trials

Mahboobeh Safaeian, Xavier Castellsagué, Allan Hildesheim, Sholom Wacholder, Mark H. Schiffman, Marie Cécile Bozonnat, Laurence Baril, Dominique Rosillon, A. Chatterjee, S. N. Chow, N. De Carvalho, Del Rosario Raymundo, F. Diaz Mitoma, G. Dubin, S. Garland, M. J. Germar, P. Gonzalez, D. M. Harper, U. Jaisamrarn, A. R. KreimerM. Lehtinen, P. Naud, J. Paavonen, K. Peters, W. Poppe, C. Porras, J. Salmeròn, Mark E. Sherman, S. R. Skinner, F. Struyf, J. Teixeira, W. Tjalma, C. M. Wheeler

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Background Studies on the role of antibodies produced after infection with human papillomavirus 18 (HPV-18) and subsequent protection from HPV-18 infection have been conflicting, mainly due to inadequate sample size. Methods We pooled data from the control arms of the Costa Rica Vaccine Trial and the PATRICIA trial. Using Poisson regression we compared the risk of newly detected 1-time HPV-18 infection, HPV-18 1-year persistent infection (12MPI), and HPV-18-associated atypical squamous cells of undetermined significance or greater (ASC-US+) lesions between HPV-18 seropositive and seronegative women. Results High HPV-18 antibodies at enrollment was associated with reduced subsequent HPV-18 detection (P trend = 0.001; relative rate [RR] = 0.69; 95% confidence interval [CI], 0.47-1.01 for the third quartile; RR = 0.63; 95% CI, 0.43-0.94 for the fourth quartile, compared to seronegative). The risk of 12MPI showed a decreasing trend with increasing antibodies (P trend = 0.06; RR = 0.72; 95% CI, 0.29-1.77; RR = 0.42; 95% CI, 0.13-1.32 for the third and fourth quartiles, respectively). Lastly, we observed a significant decreased risk of HPV-18 ASC-US+ with increasing antibody (P trend = 0.01; RR = 0.46; 95% CI, 0.21-0.97 for the fourth quartile). We also observed a significant decreased risk of HPV-16 infection, 12MPI, and ASC-US+ with increasing HPV-16 antibody level. Conclusions High HPV-18 naturally acquired antibodies were associated with partial protection from future HPV-18 infections and associated lesions. Clinical Trials Registration NCT00128661 and NCT001226810.

Original languageEnglish (US)
Pages (from-to)84-94
Number of pages11
JournalJournal of Infectious Diseases
Volume218
Issue number1
DOIs
StatePublished - Jun 5 2018

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Human papillomavirus 18
Human papillomavirus 16
Clinical Trials
Antibodies
Infection
Papillomavirus Infections
Confidence Intervals
Costa Rica
Sample Size
Vaccines

Keywords

  • HPV
  • human papillomavirus
  • immunity
  • naturally acquired antibodies

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

Cite this

Risk of HPV-16/18 Infections and Associated Cervical Abnormalities in Women Seropositive for Naturally Acquired Antibodies : Pooled Analysis Based on Control Arms of Two Large Clinical Trials. / Safaeian, Mahboobeh; Castellsagué, Xavier; Hildesheim, Allan; Wacholder, Sholom; Schiffman, Mark H.; Bozonnat, Marie Cécile; Baril, Laurence; Rosillon, Dominique; Chatterjee, A.; Chow, S. N.; De Carvalho, N.; Raymundo, Del Rosario; Mitoma, F. Diaz; Dubin, G.; Garland, S.; Germar, M. J.; Gonzalez, P.; Harper, D. M.; Jaisamrarn, U.; Kreimer, A. R.; Lehtinen, M.; Naud, P.; Paavonen, J.; Peters, K.; Poppe, W.; Porras, C.; Salmeròn, J.; Sherman, Mark E.; Skinner, S. R.; Struyf, F.; Teixeira, J.; Tjalma, W.; Wheeler, C. M.

In: Journal of Infectious Diseases, Vol. 218, No. 1, 05.06.2018, p. 84-94.

Research output: Contribution to journalArticle

Safaeian, M, Castellsagué, X, Hildesheim, A, Wacholder, S, Schiffman, MH, Bozonnat, MC, Baril, L, Rosillon, D, Chatterjee, A, Chow, SN, De Carvalho, N, Raymundo, DR, Mitoma, FD, Dubin, G, Garland, S, Germar, MJ, Gonzalez, P, Harper, DM, Jaisamrarn, U, Kreimer, AR, Lehtinen, M, Naud, P, Paavonen, J, Peters, K, Poppe, W, Porras, C, Salmeròn, J, Sherman, ME, Skinner, SR, Struyf, F, Teixeira, J, Tjalma, W & Wheeler, CM 2018, 'Risk of HPV-16/18 Infections and Associated Cervical Abnormalities in Women Seropositive for Naturally Acquired Antibodies: Pooled Analysis Based on Control Arms of Two Large Clinical Trials', Journal of Infectious Diseases, vol. 218, no. 1, pp. 84-94. https://doi.org/10.1093/infdis/jiy112
Safaeian, Mahboobeh ; Castellsagué, Xavier ; Hildesheim, Allan ; Wacholder, Sholom ; Schiffman, Mark H. ; Bozonnat, Marie Cécile ; Baril, Laurence ; Rosillon, Dominique ; Chatterjee, A. ; Chow, S. N. ; De Carvalho, N. ; Raymundo, Del Rosario ; Mitoma, F. Diaz ; Dubin, G. ; Garland, S. ; Germar, M. J. ; Gonzalez, P. ; Harper, D. M. ; Jaisamrarn, U. ; Kreimer, A. R. ; Lehtinen, M. ; Naud, P. ; Paavonen, J. ; Peters, K. ; Poppe, W. ; Porras, C. ; Salmeròn, J. ; Sherman, Mark E. ; Skinner, S. R. ; Struyf, F. ; Teixeira, J. ; Tjalma, W. ; Wheeler, C. M. / Risk of HPV-16/18 Infections and Associated Cervical Abnormalities in Women Seropositive for Naturally Acquired Antibodies : Pooled Analysis Based on Control Arms of Two Large Clinical Trials. In: Journal of Infectious Diseases. 2018 ; Vol. 218, No. 1. pp. 84-94.
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abstract = "Background Studies on the role of antibodies produced after infection with human papillomavirus 18 (HPV-18) and subsequent protection from HPV-18 infection have been conflicting, mainly due to inadequate sample size. Methods We pooled data from the control arms of the Costa Rica Vaccine Trial and the PATRICIA trial. Using Poisson regression we compared the risk of newly detected 1-time HPV-18 infection, HPV-18 1-year persistent infection (12MPI), and HPV-18-associated atypical squamous cells of undetermined significance or greater (ASC-US+) lesions between HPV-18 seropositive and seronegative women. Results High HPV-18 antibodies at enrollment was associated with reduced subsequent HPV-18 detection (P trend = 0.001; relative rate [RR] = 0.69; 95{\%} confidence interval [CI], 0.47-1.01 for the third quartile; RR = 0.63; 95{\%} CI, 0.43-0.94 for the fourth quartile, compared to seronegative). The risk of 12MPI showed a decreasing trend with increasing antibodies (P trend = 0.06; RR = 0.72; 95{\%} CI, 0.29-1.77; RR = 0.42; 95{\%} CI, 0.13-1.32 for the third and fourth quartiles, respectively). Lastly, we observed a significant decreased risk of HPV-18 ASC-US+ with increasing antibody (P trend = 0.01; RR = 0.46; 95{\%} CI, 0.21-0.97 for the fourth quartile). We also observed a significant decreased risk of HPV-16 infection, 12MPI, and ASC-US+ with increasing HPV-16 antibody level. Conclusions High HPV-18 naturally acquired antibodies were associated with partial protection from future HPV-18 infections and associated lesions. Clinical Trials Registration NCT00128661 and NCT001226810.",
keywords = "HPV, human papillomavirus, immunity, naturally acquired antibodies",
author = "Mahboobeh Safaeian and Xavier Castellsagu{\'e} and Allan Hildesheim and Sholom Wacholder and Schiffman, {Mark H.} and Bozonnat, {Marie C{\'e}cile} and Laurence Baril and Dominique Rosillon and A. Chatterjee and Chow, {S. N.} and {De Carvalho}, N. and Raymundo, {Del Rosario} and Mitoma, {F. Diaz} and G. Dubin and S. Garland and Germar, {M. J.} and P. Gonzalez and Harper, {D. M.} and U. Jaisamrarn and Kreimer, {A. R.} and M. Lehtinen and P. Naud and J. Paavonen and K. Peters and W. Poppe and C. Porras and J. Salmer{\`o}n and Sherman, {Mark E.} and Skinner, {S. R.} and F. Struyf and J. Teixeira and W. Tjalma and Wheeler, {C. M.}",
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TY - JOUR

T1 - Risk of HPV-16/18 Infections and Associated Cervical Abnormalities in Women Seropositive for Naturally Acquired Antibodies

T2 - Pooled Analysis Based on Control Arms of Two Large Clinical Trials

AU - Safaeian, Mahboobeh

AU - Castellsagué, Xavier

AU - Hildesheim, Allan

AU - Wacholder, Sholom

AU - Schiffman, Mark H.

AU - Bozonnat, Marie Cécile

AU - Baril, Laurence

AU - Rosillon, Dominique

AU - Chatterjee, A.

AU - Chow, S. N.

AU - De Carvalho, N.

AU - Raymundo, Del Rosario

AU - Mitoma, F. Diaz

AU - Dubin, G.

AU - Garland, S.

AU - Germar, M. J.

AU - Gonzalez, P.

AU - Harper, D. M.

AU - Jaisamrarn, U.

AU - Kreimer, A. R.

AU - Lehtinen, M.

AU - Naud, P.

AU - Paavonen, J.

AU - Peters, K.

AU - Poppe, W.

AU - Porras, C.

AU - Salmeròn, J.

AU - Sherman, Mark E.

AU - Skinner, S. R.

AU - Struyf, F.

AU - Teixeira, J.

AU - Tjalma, W.

AU - Wheeler, C. M.

PY - 2018/6/5

Y1 - 2018/6/5

N2 - Background Studies on the role of antibodies produced after infection with human papillomavirus 18 (HPV-18) and subsequent protection from HPV-18 infection have been conflicting, mainly due to inadequate sample size. Methods We pooled data from the control arms of the Costa Rica Vaccine Trial and the PATRICIA trial. Using Poisson regression we compared the risk of newly detected 1-time HPV-18 infection, HPV-18 1-year persistent infection (12MPI), and HPV-18-associated atypical squamous cells of undetermined significance or greater (ASC-US+) lesions between HPV-18 seropositive and seronegative women. Results High HPV-18 antibodies at enrollment was associated with reduced subsequent HPV-18 detection (P trend = 0.001; relative rate [RR] = 0.69; 95% confidence interval [CI], 0.47-1.01 for the third quartile; RR = 0.63; 95% CI, 0.43-0.94 for the fourth quartile, compared to seronegative). The risk of 12MPI showed a decreasing trend with increasing antibodies (P trend = 0.06; RR = 0.72; 95% CI, 0.29-1.77; RR = 0.42; 95% CI, 0.13-1.32 for the third and fourth quartiles, respectively). Lastly, we observed a significant decreased risk of HPV-18 ASC-US+ with increasing antibody (P trend = 0.01; RR = 0.46; 95% CI, 0.21-0.97 for the fourth quartile). We also observed a significant decreased risk of HPV-16 infection, 12MPI, and ASC-US+ with increasing HPV-16 antibody level. Conclusions High HPV-18 naturally acquired antibodies were associated with partial protection from future HPV-18 infections and associated lesions. Clinical Trials Registration NCT00128661 and NCT001226810.

AB - Background Studies on the role of antibodies produced after infection with human papillomavirus 18 (HPV-18) and subsequent protection from HPV-18 infection have been conflicting, mainly due to inadequate sample size. Methods We pooled data from the control arms of the Costa Rica Vaccine Trial and the PATRICIA trial. Using Poisson regression we compared the risk of newly detected 1-time HPV-18 infection, HPV-18 1-year persistent infection (12MPI), and HPV-18-associated atypical squamous cells of undetermined significance or greater (ASC-US+) lesions between HPV-18 seropositive and seronegative women. Results High HPV-18 antibodies at enrollment was associated with reduced subsequent HPV-18 detection (P trend = 0.001; relative rate [RR] = 0.69; 95% confidence interval [CI], 0.47-1.01 for the third quartile; RR = 0.63; 95% CI, 0.43-0.94 for the fourth quartile, compared to seronegative). The risk of 12MPI showed a decreasing trend with increasing antibodies (P trend = 0.06; RR = 0.72; 95% CI, 0.29-1.77; RR = 0.42; 95% CI, 0.13-1.32 for the third and fourth quartiles, respectively). Lastly, we observed a significant decreased risk of HPV-18 ASC-US+ with increasing antibody (P trend = 0.01; RR = 0.46; 95% CI, 0.21-0.97 for the fourth quartile). We also observed a significant decreased risk of HPV-16 infection, 12MPI, and ASC-US+ with increasing HPV-16 antibody level. Conclusions High HPV-18 naturally acquired antibodies were associated with partial protection from future HPV-18 infections and associated lesions. Clinical Trials Registration NCT00128661 and NCT001226810.

KW - HPV

KW - human papillomavirus

KW - immunity

KW - naturally acquired antibodies

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DO - 10.1093/infdis/jiy112

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