Elsevier

Vaccine

Volume 30, Supplement 5, 20 November 2012, Pages F12-F23
Vaccine

Review
Global Burden of Human Papillomavirus and Related Diseases

https://doi.org/10.1016/j.vaccine.2012.07.055Get rights and content

Abstract

The worldwide prevalence of infection with human papillomavirus (HPV) in women without cervical abnormalities is 11–12% with higher rates in sub-Saharan Africa (24%), Eastern Europe (21%) and Latin America (16%). The two most prevalent types are HPV16 (3.2%) and HPV18 (1.4%). Prevalence increases in women with cervical pathology in proportion to the severity of the lesion reaching around 90% in women with grade 3 cervical intraepithelial neoplasia and invasive cancer. HPV infection has been identified as a definite human carcinogen for six types of cancer: cervix, penis, vulva, vagina, anus and oropharynx (including the base of the tongue and tonsils). Estimates of the incidence of these cancers for 2008 due to HPV infection have been calculated globally. Of the estimated 12.7 million cancers occurring in 2008, 610,000 (Population Attributable Fraction [PAF] = 4.8%) could be attributed to HPV infection. The PAF varies substantially by geographic region and level of development, increasing to 6.9% in less developed regions of the world, 14.2% in sub-Saharan Africa and 15.5% in India, compared with 2.1% in more developed regions, 1.6% in Northern America and 1.2% in Australia/New Zealand. Cervical cancer, for which the PAF is estimated to be 100%, accounted for 530,000 (86.9%) of the HPV attributable cases with the other five cancer types accounting for the residual 80,000 cancers. Cervical cancer is the third most common female malignancy and shows a strong association with level of development, rates being at least four-fold higher in countries defined within the low ranking of the Human Development Index (HDI) compared with those in the very high category. Similar disparities are evident for 5-year survival—less than 20% in low HDI countries and more than 65% in very high countries. There are five-fold or greater differences in incidence between world regions. In those countries for which reliable temporal data are available, incidence rates appear to be consistently declining by approximately 2% per annum. There is, however, a lack of information from low HDI countries where screening is less likely to have been successfully implemented. Estimates of the projected incidence of cervical cancer in 2030, based solely on demographic factors, indicate a 2% increase in the global burden of cervical cancer, i.e., in balance with the current rate of decline. Due to the relative small numbers involved, it is difficult to discern temporal trends for the other cancers associated with HPV infection. Genital warts represent a sexually transmitted benign condition caused by HPV infection, especially HPV6 and HPV11. Reliable surveillance figures are difficult to obtain but data from developed countries indicate an annual incidence of 0.1 to 0.2% with a peak occurring at teenage and young adult ages.

This article forms part of a special supplement entitled “Comprehensive Control of HPV Infections and Related Diseases” Vaccine Volume 30, Supplement 5, 2012.

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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