Abstract
BackgroundSeveral serological assays have been developed to detect antibodies elicited against infections with oncogenic human papillomavirus (HPV) type 16. The association between antibody levels measured by various assays and subsequent HPV infection risk may differ. We compared HPV16-specific antibody levels previously measured by a virus-like particle (VLP)-based direct enzyme-linked immunoassay (ELISA) with levels measured by additional assays and evaluated the protection against HPV16 infection conferred at different levels of the assays.Methodology/Principal FindingsReplicate enrollment serum aliquots from 388 unvaccinated women in the control arm of the Costa Rica HPV vaccine trial were measured for HPV16 seropositivity using three serological assays: a VLP-based direct ELISA; a VLP-based competitive Luminex immunoassay (cLIA); and a secreted alkaline phosphatase protein neutralization assay (SEAP-NA). We assessed the association of assay seropositivity and risk of subsequent HPV16 infection over four years of follow-up by calculating sampling-adjusted odds ratios (OR) and HPV16 seropositivity based on standard cutoff from the cLIA was significantly associated with protection from subsequent HPV16 infection (OR = 0.48, CI = 0.27–0.86, compared with seronegatives). Compared with seronegatives, the highest seropositive tertile antibody levels from the direct ELISA (OR = 0.53, CI = 0.28–0.90) as well as the SEAP-NA (OR = 0.20, CI = 0.06, 0.64) were also significantly associated with protection from HPV16 infection.Conclusions/SignificanceEnrollment HPV16 seropositivity by any of the three serological assays evaluated was associated with protection from subsequent infection, although cutoffs for immune protection were different. We defined the assays and seropositivity levels after natural infection that better measure and translate to protective immunity.
Highlights
Infection with carcinogenic human papillomaviruses (HPV), most notably types 16 and 18, is necessary for the development of cervical cancer [1], the third most common cancer in women worldwide [2]
Using these sampling-adjusted population estimates, we found that 9% of the individuals who were categorized as seropositive using laboratory-based standard cutoffs by the direct enzyme-linked immunoassay (ELISA), 5% by the competitive Luminex immunoassay (cLIA), and 7% by the secreted alkaline phosphatase protein neutralization assay (SEAP-NA) developed an incident infection; by contrast, 11% of individuals who were categorized as seronegative by each assay developed an incident infection
Enrollment HPV16 seropositivity by cLIA was significantly associated with protection from incident HPV16 infection (OR = 0.48, 95% CI = 0.27–0.86, compared with seronegatives)
Summary
Infection with carcinogenic human papillomaviruses (HPV), most notably types 16 and 18, is necessary for the development of cervical cancer [1], the third most common cancer in women worldwide [2]. Because of the role of antibodies in preventing HPV infections, serological assays are important for measuring the antibodies or other immune factors directed against HPV, and these assays may identify the individuals who had mounted an immune response to previous exposure to HPV and may be protected against subsequent HPV infection [9]. Several serological assays have been developed to detect antibodies elicited against infections with oncogenic human papillomavirus (HPV) type 16. The association between antibody levels measured by various assays and subsequent HPV infection risk may differ. We compared HPV16-specific antibody levels previously measured by a virus-like particle (VLP)-based direct enzyme-linked immunoassay (ELISA) with levels measured by additional assays and evaluated the protection against HPV16 infection conferred at different levels of the assays
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