Seroprevalence of seven high-risk HPV types in The Netherlands

doi:10.1016/j.vaccine.2012.08.068

Vaccine

Volume 30, Issue 47, 19 October 2012, Pages 6686-6693

https://doi.org/10.1016/j.vaccine.2012.08.068 Get rights and content

Abstract

Background

To obtain insight into the age-specific seroprevalence for seven high-risk human papillomavirus (hr-HPV) serotypes (HPV16, 18, 31, 33, 45, 52, and 58) among the general population in the pre-vaccination era in The Netherlands.

Methods

From a cross-sectional population-based study (ISRCTN 20164309) performed in 2006/2007 6384 sera of men, women and children were tested for seven hr-HPV specific antibodies using a fluorescent bead-based multiplex immunoassay with virus-like particles of the seven HPV serotypes.

Results

An increase in seroprevalence was observed in adolescents, especially for the most prevalent HPV type 16 (up to 11.3%). The increase was most pronounced in women, but was less clear for the other six HPV serotypes. Relatively stable seroprevalences were found in the middle aged cohorts and a slight decrease in the elderly. For the age cohorts >14 years, the seroprevalence among women (25.2%) was higher compared with men (20.3%) (p = 0.0002). We found that 10.1% of the population was seropositive for multiple HPV serotypes.

Conclusions

The HPV vaccination program is targeted at preadolescents as is justified by the results in this study in which a step-up in HPV seroprevalence is observed at ages of sexual debut. Although direct interpretation of seroprevalence data are hampered by cross-reactivity and seroconversion rate, these data are useful as baseline to evaluate long-term population effects of the HPV16/18 vaccination program.

Highlights

► Pre-HPV vaccine antibody levels serve as baseline to evaluate long-term HPV vaccination effects. ► The increase in HPV seroprevalence in adolescents correlates with sexual debut, mainly for HPV16 in women. ► 10% of the population was found seropositive for multiple HPV serotypes. ► Ethnicity, marital status, casual partnership or having a STD increased the risk of HPV seropositivity.

Introduction

Human papilloma virus (HPV) is one of the most common sexually transmitted pathogens worldwide. From the general population it is established that 80% will be infected at some time during their live [1]. More than 100 different HPV genotypes have been identified, of which 40 infect the genital tract [2]. High-risk (hr) HPV, such as types 16 and 18, can cause cervical cancer and other genital cancers, and also oro-pharyngeal cancer. HPV16 and HPV18 are the most common HPV types detected in women worldwide and are responsible for 70% of all cervical cancer cases [1], [2], [3]. When infected with HPV, most genital transient HPV infections regress within two years [4]. Only a small proportion of infected individuals suffer from persistent infections and they are at risk for cervical cancer [5], [6].

Assays developed for the detection of HPV specific IgG antibodies to virus-like-particles (VLPs), have been used for seroprevalence studies in several countries [7], [8], [9]. Not all HPV infected individuals seroconvert and 20–50% of the women who are carriers of HPV DNA do not have detectable HPV antibodies in their serum [1], [3]. When HPV antibody responses develop after a natural HPV infection, they are relatively stable over time [10]. Therefore, the measurement of HPV specific antibodies will be useful to provide information about the HPV seroprevalence in population studies and can be used to estimate lifetime cumulative HPV exposure and past HPV infections.

In this study we describe the age-specific seroprevalence of seven hr-HPV types (16, 18, 31, 33, 45, 52 and 58) and the risk-factors associated with seroprevalence in a representative sample of the Dutch population before the implementation of the HPV vaccine in the national immunization program (NIP). In The Netherlands, HPV vaccination (Cervarix) was included in the NIP in 2010 for girls 12 years of age with vaccination coverage of 50% [11]. In addition, a catch-up vaccination campaign was performed for girls 13–16 years of age. Age-specific seroprevalence data from the pre-vaccination era in The Netherlands are scarce. Previous studies in The Netherlands were limited to the number of HPV types (only 6, 11, 16 and 18), age groups or focused only on a specific city (Amsterdam) in The Netherlands [12], [13]. Our study provides insight in risk factors associated with seropositivity, in the distribution of high-risk HPV types and is valuable in the evaluation of long-term population effects of the HPV16/18 vaccination program.

Section snippets

Study population

Serum samples from a cross-sectional population-based serosurveillance study performed from February 2006 to June 2007 were available (n = 6384) for analysis. Participants, women and men, were 0–79 years of age. The study design has been described previously [14]. Briefly, a total of 19,781 individuals were invited into the study of which 6386 (32%) participated. Two sera were not available for analysis (0.03%) because serum quality was not sufficient. The age strata 0 and 1–4 years and

Characteristics of the total study sample

Samples from the pre-HPV vaccination period were collected between February 2006 and June 2007, a median of 2.8 years before the introduction of HPV vaccination in The Netherlands in March 2010. Participants were 0–79 years of age. In this study 54% of the participants were female (n = 3473) and 46% were male (n = 2911).

HPV-MIA characteristics and cut-off values

The mean coefficient of variation (CV) for the intra-assay plate-to-plate variation and variation within a plate was 8% and 7%, respectively, while the inter-assay variation,

Discussion

Here we describe the cross-sectional seroprevalence of antibodies to hr-HPV types 16, 18, 31, 33, 45, 52, and 58 in a pre-vaccination era in women, men and children in The Netherlands. We found a step-up in the overall seroprevalence for any HPV serotype in the age cohorts of 15–19 to 20–24 years. This step-up was most pronounced for HPV16 and less clear for the other HPV serotypes. A decreasing trend was observed in the seroprevalence from 50 years onwards. The overall seroprevalence was

Summary

This study provides information about the seroepidemiology of seven high-risk HPV serotypes in The Netherlands before vaccine implementation for evaluation of the current vaccination strategy.

Acknowledgement

Conflict of interest: All authors declared no conflict of interest.

Financial support: Unrestricted grant of MSD (study code HPV01E).

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Previous studies were mainly performed in highly selected populations and focused on DNA prevalence in young women (Delere et al., 2014; Hauck et al., 2015; Iftner et al., 2010; Petry et al., 2013; Remschmidt et al., 2013). Worldwide, only a few population-based studies have focused on type-specific seroprevalence in men and women (Liu et al., 2016; Markowitz et al., 2009; Newall et al., 2008; Scherpenisse et al., 2012). The aim of our study was to determine the seroprevalence and associated risk factors of 19 HPV types in 18–79 year-old women and men living in Germany during the prevaccine era, using blood samples from a large countrywide population-based survey.
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Seroprevalence of seven high-risk HPV types in The Netherlands

Abstract

Background

Methods

Results

Conclusions

Highlights

Introduction

Section snippets

Study population

Characteristics of the total study sample

HPV-MIA characteristics and cut-off values

Discussion

Summary

Acknowledgement

Lancet Infect Dis

Vaccine

J Immunol Methods

Virology

Lancet Infect Dis

J Adolesc Health

The natural history of cervical HPV infection: unresolved issues

Nat Rev Cancer

HPV: immune response to infection and vaccination

Infect Agent Cancer

The epidemiology of genital human papillomavirus infection

Vaccine

Epidemiologic evidence showing that human papillomavirus infection causes most cervical intraepithelial neoplasia

J Natl Cancer Inst

Persistent genital human papillomavirus infection as a risk factor for persistent cervical dysplasia

J Natl Cancer Inst

Prevalence of human papillomavirus antibodies in young female subjects in England

Br J Cancer

Seroprevalence of human papillomavirus types 6, 11, 16, and 18 in the United States: National Health and Nutrition Examination Survey 2003–2004

J Infect Dis

Seroprevalence of 34 human papillomavirus types in the German general population

PLoS Pathog

Stability over time of serum antibody levels to human papillomavirus type 16

J Infect Dis

Seroprevalence and determinants of eight high-risk human papillomavirus types in homosexual men, heterosexual men, and women: a population-based study in Amsterdam

Sex Transm Dis