Risk of newly detected infections and cervical abnormalities in adult women seropositive or seronegative for naturally acquired HPV-16/18 antibodies

Dominique Rosillon (Corresponding Author), Laurence Baril, Maria Rowena Del Rosario-Raymundo, Cosette Marie Wheeler, Susan Rachel Skinner, Suzanne Marie Garland, Jorge Salmeron, Eduardo Lazcano-Ponce, Carlos Santiago Vallejos, Tanya Stoney, Bram ter Harmsel, Timothy Yong Kuei Lim, Swee Chong Quek, Galina Minkina, Shelly Ann McNeil, Celine Bouchard, Kah Leng Fong, Deborah Money, Arunachalam Ilancheran, Alevtina SavichevaMargaret Cruickshank, Archana Chatterjee, Alison Fiander, Mark Martens, Marie Cecile Bozonnat, Frank Struyf, Gary Dubin, Xavier Castellsagué

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Abstract

Abstract Background Infections with human papillomavirus (HPV) types 16 and 18 account for ~70% of invasive cervical cancers but the degree of protection from naturally acquired anti-HPV antibodies is uncertain. We examined the risk of HPV infections as defined by HPV DNA detection and cervical abnormalities among women >25 years in the Human Papilloma VIrus Vaccine Immunogenicity ANd Efficacy trial's (VIVIANE, NCT00294047) control arm. Methods Serum anti-HPV-16/18 antibodies were determined at baseline and every 12 months in baseline DNA-negative women (N = 2687 for HPV-16 and 2705 for HPV-18) by enzyme-linked immunosorbent assay (ELISA) from blood samples. HPV infections were identified by polymerase chain reaction (PCR) every 6-months, and cervical abnormalities were confirmed by cytology every 12 months. Data were collected over a 7-year period. The association between the risk of type-specific infection and cervical abnormalities and serostatus was assessed using Cox proportional hazard models. Results Risk of newly detected HPV-16-associated 6-month persistent infections (PI) (hazard ratio [HR] = 0.56 [95%CI:0.32; 0.99]) and atypical squamous cells of undetermined significance (ASC-US+) (HR = 0.28 [0.12; 0.67]) were significantly lower in baseline seropositive vs baseline seronegative women. HPV-16-associated incident infections (HR = 0.81 [0.56; 1.16]) and 12-month PI (HR = 0.53 [0.24; 1.16]) showed the same trend. A similar trend of lower risk was observed in HPV-18-seropositive vs -seronegative women (HR = 0.95 [0.59; 1.51] for IIs, HR = 0.43 [0.16; 1.13] for 6-month PIs, HR = 0.31 [0.07; 1.36] for 12-month PIs, and HR = 0.61 [0.23; 1.61] for ASC-US+). Conclusions Naturally acquired anti-HPV-16 antibodies were associated with a decreased risk of subsequent infection and cervical abnormalities in women >25 years. This possible protection was lower than that previously reported in 15- to 25-year-old women.
Original languageEnglish
Pages (from-to)4938-4953
Number of pages15
JournalCancer Medicine
Volume8
Issue number10
Early online date5 Jul 2019
DOIs
Publication statusPublished - Aug 2019

Keywords

  • human papillomavirus infection
  • naturally acquired antibodies
  • redetection or reactivation of HPV infection
  • cervical abnormality
  • risk reduction
  • IMMUNITY
  • EFFICACY
  • SUBSEQUENT HPV INFECTION
  • OLDER
  • FOLLOW-UP
  • SERUM ANTIBODIES
  • CONTROL ARM
  • DOUBLE-BLIND
  • HUMAN-PAPILLOMAVIRUS INFECTION
  • 16/18 AS04-ADJUVANTED VACCINE

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    Rosillon, D., Baril, L., Del Rosario-Raymundo, M. R., Wheeler, C. M., Skinner, S. R., Garland, S. M., Salmeron, J., Lazcano-Ponce, E., Vallejos, C. S., Stoney, T., ter Harmsel, B., Lim, T. Y. K., Quek, S. C., Minkina, G., McNeil, S. A., Bouchard, C., Fong, K. L., Money, D., Ilancheran, A., ... Castellsagué, X. (2019). Risk of newly detected infections and cervical abnormalities in adult women seropositive or seronegative for naturally acquired HPV-16/18 antibodies. Cancer Medicine, 8(10), 4938-4953. https://doi.org/10.1002/cam4.1879