Elsevier

Vaccine

Volume 26, Supplement 10, 19 August 2008, Pages K1-K16
Vaccine

ICO Monograph Series on HPV and Cervical Cancer: General Overview
Epidemiology and Natural History of Human Papillomavirus Infections and Type-Specific Implications in Cervical Neoplasia

https://doi.org/10.1016/j.vaccine.2008.05.064Get rights and content

Abstract

Worldwide human papillomavirus (HPV) prevalence in women with normal cytology at any given point in time is approximately 10% indicating that HPV is one of the most common sexually transmitted infections. HPV-16 is consistently the most common type and HPV-18 the second with some minor regional differences. Furthermore, across the spectrum of cervical lesions, HPV-16 is consistently the most common HPV type contributing to 50–55% of invasive cervical cancer cases strongly suggesting that this viral type has a biological advantage for transmission, persistency and transformation. The same phenomenon is observed albeit at a lower level for HPV-18 and HPV-45.

Sexual behavioral patterns across age groups and populations are central to the description of the HPV circulation and of the risk of infection. The concept of group sexual behavior (in addition to individual sexual behavior) is important in exploring HPV transmission and has implications for defining and monitoring HPV and cancer prevention strategies.

In natural history studies, the pattern of HPV DNA prevalence by age groups is similar to the patterns of HPV incidence. Rates of exposure in young women are high and often include multiple types. There is a spontaneous and rapid decrease of the HPV DNA detection rates in the middle-age groups followed by a second rise in the post-menopausal years. This article reviews: 1) the evidence in relation to the burden of HPV infections in the world and the contributions of each HPV type to the spectrum of cervical cellular changes spanning from normal cytology to invasive cervical cancer; 2) the critical role of the patterns of sexual behavior in the populations; and 3) selected aspects of the technical and methodological complexity of natural history studies of HPV and cervical neoplasia.

Introduction

Epidemiological and natural history studies continue to contribute important information for the definition of sustainable strategies for cervical cancer prevention. This article reviews the evidence in relation to the burden of human papillomavirus (HPV) infections in the world and contributions of individual HPV types to the spectrum of cervical cellular changes spanning from normal cytology to invasive cervical cancer (ICC). In the context of HPV infections, it is also important to consider other significant topics which influence HPV infection and its transmission. We provide a summary of novel data on sexual behavior patterns including the impact of migration between populations highlighting the complexities of HPV transmission and cervical cancer diagnosis. Natural history research is now focusing on detailed aspects of the viral and host interactions such as viral persistency and duration of infections, identification of intermediate biomarkers and the notion of viral latency. We describe some of the key results from extended years of follow-up in cohort studies and have tried to depict clinical and research implications and outstanding research issues.

Section snippets

Women with normal cytology

Most women in the world will be infected with HPV at some time during their lifetime. The most comprehensive available data on the HPV prevalence in women with normal cytology derives from a large, global meta-analysis of the literature published in 2007 and compiled by the World Health Organization (WHO)/Catalan Institute of Oncology (ICO) Information Centre on HPV and cervical cancer (http://www.who.int/hpvcentre/en/) (Table 1) [1], [2]. The study includes publications from 1999 up to early

Key patterns of sexual behavior and geographical variation

Global patterns of sexual behavior have recently been summarized in an analysis of data from surveys in 59 countries. The study is based on nationally representative population-based samples of men and women on reproductive and sexual health practices [7]. One of the main findings from this landmark study is the absence of a pattern for decreasing age at sexual debut. Sexual debut most commonly occurs in the late teenage years and women tend to be younger than men in cultures where early

Updating the HPV natural history findings from cohort studies

We continue to learn about the natural history of carcinogenic cervical HPV infections from follow-up of longitudinal cohorts with appropriate HPV genotyping methods. Standardization of cell collection methods, buffers, and genotyping methods (primarily PCR) between research teams has led to a convergence and confirmation of trustworthy basic patterns. There is still difficulty with the reliability of HPV typing of low viral load infections, particularly when multiple types are present, which

Conclusion

Worldwide, HPV-16 is the most common HPV type across the spectrum of HPV related cervical lesions. The increase in the relative contribution of HPV-16 from 2-4 % in women with normal cytology to 50–55% in ICC supports the notion of its biological advantage for transmission and transformation. The same phenomenon is observed at a lower level for HPV-18 and HPV-45. In women with ICC, the most common HPV types are HPV-16, 18, 33, 45, 31 and 58. HPV-16, 18 and 45 are the three most relevant types

Disclosed potential conflicts of interest

FXB: Advisory Board (GlaxoSmithKline, Merck and Co., Inc., Sanofi Pasteur MSD); Speakers Bureau (GlaxoSmithKline); Research Grants (Merck and Co., Inc., Sanofi Pasteur MSD).

ARG: Advisory Board (Merck and Co., Inc.); Research Grants (Merck and Co., Inc.); Speakers Bureau (Merck and Co., Inc.).

SS: Research Grants (Merck & Co. Inc., Sanofi-Pasteur MSD).

GTL: Speakers Bureau (Merck Sharp and Dome).

SKK: Advisory Board (Sanofi-Pasteur MSD); Research Grants (Merck and Co., Inc., Sanofi-Pasteur MSD);

Acknowledgements

F. Xavier Bosch's and Silvia de Sanjose's work was partially supported by Spanish public grants from the Instituto de Salud Carlos III (grants RCESP C03/09, RTICESP C03/10 and RTIC RD06/0020/0095 and CIBERESP) and from the Agència de Gestió d’Ajuts Universitaris i de Recerca (AGAUR 2005SGR 00695. Ann N. Burchell's work is supported by the Canadian Cancer Society through a research studentship award from the National Cancer Institute of Canada. Anna R. Giuliano's work is supported by grants from

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