Seroprevalence of 34 Human Papillomavirus Types in the German General Population

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Abstract
The natural history of infections with many human papillomavirus (HPV) types is poorly understood. Here, we describe for the first time the age- and sex-dependent antibody prevalence for 29 cutaneous and five mucosal HPV types from 15 species within five phylogenetic genera (alpha, beta, gamma, mu, nu) in a general population. Sera from 1,797 German adults and children (758 males and 1,039 females) between 1 and 82 years (median 37 years) were analysed for antibodies to the major capsid protein L1 by Luminex-based multiplex serology. The first substantial HPV antibody reactions observed already in children and young adults are those to cutaneous types of the genera nu (HPV 41) and mu (HPV 1, 63). The antibody prevalence to mucosal high-risk types, most prominently HPV 16, was elevated after puberty in women but not in men and peaked between 25 and 34 years. Antibodies to beta and gamma papillomaviruses (PV) were rare in children and increased homogeneously with age, with prevalence peaks at 40 and 60 years in women and 50 and 70 years in men. Antibodies to cutaneous alpha PV showed a heterogeneous age distribution. In summary, these data suggest three major seroprevalence patterns for HPV of phylogenetically distinct genera: antibodies to mu and nu skin PV appear early in life, those to mucosal alpha PV in women after puberty, and antibodies to beta as well as to gamma skin PV accumulate later in life. Papillomaviruses (PV) are a large and highly diverse group of DNA viruses that infect cutaneous and mucosal epithelia of warm-blooded vertebrates. Of the more than 100 identified human PV (HPV) types, many cause benign lesions like warts and papillomas, and some also cervical, other anogenital, and oral cancers. For most HPV, transmission routes, pathogenesis, and time and duration of infection are only poorly understood. In the German general population, we investigated the prevalence of antibodies to the capsid proteins of 34 HPV types representative of all five PV genera (alpha, beta, gamma, mu, and nu) that contain HPV. We provide evidence for different age- and sex-dependent seroprevalence patterns of phylogenetically related HPV: antibodies to cutaneous mu and nu PV appear early in life, those to mucosal alpha PV after puberty, and those to beta and gamma skin PV accumulate in adulthood.

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