ReviewGlobal Burden of Human Papillomavirus and Related Diseases
Highlights
► 1 in 10 women worldwide carries an HPV infection at any point in time. ► 610,000 incident cancers per annum are attributable to HPV infection globally. ► 80.6% of HPV associated cancers occur in less developed regions of the world. ► Cervix is the predominant HPV-associated cancer with 530,000 incident cases p.a. ► Genital warts are caused by HPV with an annual incidence of 0.1 to 0.2%.
Introduction
This paper provides an overview of the worldwide prevalence of human papillomavirus (HPV) infection and the associated burden of cancer. It provides a brief review of the distribution of HPV infection by geographical region and in relation to body sites for which cancer can be an outcome of such infection (cervix, penis, vagina, vulva, anus and oropharynx). For these body sites, information has been extracted from the GLOBOCAN 2008 database on the total number of cancers diagnosed annually worldwide and this has been used to produce estimates of the proportion of these cancers that are associated with HPV. The overall burden of HPV-associated cancer has then been stratified by world region and by level of socioeconomic development. Cervical cancer is the most important type of cancer associated with HPV and the chapter provides a review of the current global descriptive epidemiology of this disease, especially in relation to level of development and, where data allows, an analysis of temporal trends. Similar trends are presented for the five other types of cancer associated with HPV infection. Consideration is also given to the epidemiology of genital warts, the major benign condition associated with HPV infection.
Section snippets
HPV prevalence
The overall global burden of HPV infection is optimally assessed by the pooling of results from studies in which reliable, quality-controlled methods have been used to detect HPV in women with normal cervical cytology. The most comprehensive such meta-analysis, with data extracted from 194 studies and based on testing over one million women using polymerase chain reaction (PCR) or Hybrid Capture® 2 (Qiagen Gaithersburg, Inc., MD, USA [formerly known as Digene Corp.]) for HPV detection,
Cancers attributable to HPV infection – global and regional burden and population attributable fraction estimates for 2008
Infection with high-risk HPV is recognized as one of the major causes of infection-related cancer worldwide (along with Helicobacter pylori and hepatitis viruses B and C) [10]. In this section, we consider those cancer sites for which IARC Monograph 100B [11], [12] stated that there was strong evidence for a causal etiology with HPV and for which HPV could be considered a group 1 (definite human) carcinogen. For each of these sites of cancer, the population attributable fraction (PAF) has been
Cancers attributable to HPV infection – global and regional burden of cervical cancer in 2008
Of the 610,000 cancers attributable to HPV infection worldwide, the vast majority (530,000, 86.9%) are cancers of the cervix uteri. The descriptive epidemiology of this disease provides, therefore, a characterization of the majority of HPV-associated cancer. As infection with high-risk HPV is now viewed as a necessary precondition for the development of all cervical cancer; the disease description does not require stratification into HPV-associated and non-associated sub-types.
Cervical cancer
Cancers attributable to HPV infection – temporal trends in cervical cancer
In order to examine trends over time, use has been made of sequential datasets submitted by cancer registries and published in Cancer Incidence in Five Continents (CI5C) [24]. Such data, for a selected sample of registries that have provided results for five 5-year time periods and extended in the case of the USA-Surveillance Epidemiology and End Results (SEER) populations [25], are shown in Fig. 8. The registries included represent medium (India-Mumbai, Philippines-Manila), high
Cancers attributable to HPV infection – temporal trends in cancers other than the cervix
Fig. 11 shows time trends for the other HPV-associated cancer sites (oropharynx, anus, penis, vagina and vulva) and for the same registry populations and time periods as presented in Fig. 8 for cervical cancer. As can be readily observed, the age-standardized rates for these cancers were of a different magnitude than those for cervical cancer. Whereas rates for the latter varied, depending on population and time period, from 5 to 40 per 100,000, for none of the five sites considered in Fig. 11
Genital warts
Genital warts (GW) are a sexually transmitted infection (STI) usually caused by HPV6 or HPV11. Different series have recorded differences in the distribution of HPV genotypes in GW lesions, but some of the most methodologically rigorous studies have found HPV6/11 in 96–100% of all GW lesions [31], [32], [33]. In the developed world, genital warts show similar epidemiological features to other common STIs with a peak incidence in young people aged 15–24 years [34]. Not all subjects will present
Conclusions
HPV infection is the most common STI worldwide and, in many world regions, the majority of sexually active individuals of both sexes will probably acquire it at some time during their lifetime. Variations in genital HPV prevalence by age differ substantially by population. The peak in HPV prevalence among young women should not, therefore, be viewed as the natural history of the infection but, at least in part, as a “westernization” effect (i.e., tendency to have multiple sexual partners at
Disclosed potential conflicts of interest
CJL: Has received support for travel and attending meetings form GSK and SPMSD.
LB: Institutional support: HPV vaccine trials and epidemiological studies sponsored by GlaxoSmithKline, Merck and Sanofi Pasteur MSD. Screening and HPV testing trials partially supported by Qiagen. Personal support: Travel grants to conferences occasionally granted by Sanofi Pasteur MSD.
DF, CdM, IS, JLT, JV, JF, FB, MP, SF: Have disclosed no potential conflicts of interest.
Acknowledgements
The work was partially supported by public grants from the European Commission (7th Framework Programme grant HEALTH-F3-2010-242061, PREHDICT), from the Instituto de Salud Carlos III (Spanish Government) (grants FIS PI10/02995, RCESP C03/09, RTICESP C03/10, RTIC RD06/0020/0095 and CIBERESP) and from the Agència de Gestió d’Ajuts Universitaris i de Recerca – Generalitat de Catalunya (Catalonian Government) (grants AGAUR 2005SGR00695 and AGAUR 2009SGR126), who had no role in data collection,
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