Serological indicators of human papillomavirus (HPV) infection are being used to differentiate HPV-naïve from previously infected women in vaccine and epidemiologic/clinical studies. We investigated HPV16 and 18 seroepidemiology among young, unvaccinated women aged between 18 and 25.
We conducted a cross-sectional evaluation of the enrollment visit in the ongoing community-based HPV16/18 Costa Rica Vaccine Trial. Prevaccination serum immunoglobulin G (IgG) antibodies were measured against HPV16 and HPV18 by enzyme-linked immunosorbent assay; cervical samples were tested for HPV DNA using Hybrid Capture 2 and SPF10/LiPA25. Seroprevalence and its correlates were evaluated using unconditional logistic regression.
Among 5871 nonvirginal women, HPV16 and 18 seroprevalences were 30.8% and 28.1%, HPV16 and HPV18 DNA prevalences were 8.3% and 3.2%, respectively. About 37% of HPV16 DNA-positives and 42% of HPV18 DNA-positives were seronegative. Seroprevalence increased with time since sexual debut, whereas DNA prevalence did not. The correlates of HPV16 and/or 18 seropositivity were related to sexual behaviors, particularly higher number of lifetime sexual partners. There was no evidence of assay cross-reactivity as HPV16 seroprevalence was similar (approximately 34%) among women singly infected with genetically and nongenetically related species (α9 and non-α9); likewise, seropositivity to HPV18 was similar (approximately 30%) among women singly infected with α7 and non-α7 species.
The increasing seroprevalence observed with time since first sex suggests that HPV serology is a cumulative marker of HPV exposure. However, many DNA infected women were seronegative; thus, serology is an imperfect measure of past exposure to cervical HPV, at best. Additionally, we found no evidence of assay cross-reactivity.
This study of unvaccinated women found that human papillomavirus serology is a cumulative marker of human papillomavirus exposure, though an imperfect measure of past exposure. We found no evidence of assay cross-reactivity.
From the *Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD; †Proyecto Epidemiológico Guanacaste, Fundación INCIENSA, Liberia, Costa Rica; ‡Division of Cancer Prevention, National Cancer Institute, Bethesda, MD;§GlaxoSmithKline Biologicals, Rixensart, Belgium; and ∥DDL Diagnostic Laboratory, Voorburg, The Netherlands
CVT is a long-standing collaboration between investigators in Costa Rica and NCI. The affiliations of the members of the CVT group are as follows. At the Proyecto Epidemiológico Guanacaste, Fundación INCIENSA, San José, Costa Rica, Mario Alfaro (cytologist), Manuel Barrantes (field supervisor), M. Concepcion Bratti (coinvestigator), Fernando Cárdenas (general field supervisor), Bernal Cortés (specimen and repository manager), Albert Espinoza (head, coding, and data entry), Yenory Estrada (pharmacist), Paula Gonzalez (coinvestigator), Diego Guillén (pathologist), Rolando Herrero (coprincipal investigator), Silvia E. Jimenez (trial coordinator), Jorge Morales (colposcopist), Lidia Ana Morera (head study nurse), Elmer Pérez (field supervisor), Carolina Porras (coinvestigator), Ana Cecilia Rodriguez (coinvestigator), and Maricela Villegas (clinic physician); at the University of Costa Rica, San José, Costa Rica, Enrique Freer (director, HPV Diagnostics Laboratory), Jose Bonilla (head, HPV Immunology Laboratory), Sandra Silva (head technician, HPV Diagnostics Laboratory), Ivannia Atmella (immunology technician), and Margarita Ramírez (immunology technician); at the National Cancer Institute, Bethesda, MD, Nora Macklin (trial coordinator), Allan Hildesheim (coprincipal investigator and NCI coproject officer), Douglas R. Lowy (HPV virologist), Mark Schiffman (medical monitor and NCI coproject officer), John T. Schiller (HPV virologist), Mark Sherman (quality control pathologist), Diane Solomon (medical monitor and quality control pathologist), and Sholom Wacholder (statistician); at SAIC, NCI—Frederick, Frederick, MD, Ligia Pinto (head, HPV Immunology Laboratory) and Alfonso Garcia-Pineres (scientist, HPV Immunology Laboratory); at Womens and Infants' Hospital, Providence, RI, Claire Eklund (quality control, cytology) and Martha Hutchinson (quality control, cytology); DDL Diagnostic Laboratory, Voorburg, The Netherlands, Wim Quint (HPV DNA testing) and Leen-Jan van Doorn (HPV DNA testing); and GSK Biologicals, Rixensart, Belgium Catherine Bougelet (HPV16/18 ELISA testing).
Supported by intramural NCI (N01-CP-11005) with support from the NIH Office of Research on Women's Health and is conducted in agreement with the Ministry of Health of Costa Rica. Vaccine was provided for our trial by GSK Biologicals, under a clinical trials agreement with NCI. GSK also provided support for aspects of the trial associated with the regulatory submission needs of the company under FDA BB-IND 7920. NCI and Costa Rican investigators make final editorial decisions on this presentation and subsequent publications; GSK has the right to review/comment.
Wim Quint and Leen-Jan van Doorn are employees of DDL Diagnostic Laboratory; Catherine Bougelet is an employee of GSK Biologicals. None of the authors have any potential conflicts of interest to report.
Correspondence: Sarah E. Coseo, MPH, Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, 6120 Executive Blvd, EPS, Room 7079, Rockville, MD 20852. E-mail: firstname.lastname@example.org.
Received for publication December 8, 2009, and accepted March 27, 2010.