Elsevier

Preventive Medicine

Volume 53, Supplement 1, 1 October 2011, Pages S12-S21
Preventive Medicine

Review
Epidemiology and burden of HPV infection and related diseases: Implications for prevention strategies

https://doi.org/10.1016/j.ypmed.2011.08.017Get rights and content

Abstract

Human papillomavirus (HPV) infection is a necessary, although not sufficient cause of cervical cancer. Globally, HPV infection accounts for an estimated 530,000 cervical cancer cases (~ 270,000 deaths) annually, with the majority (86% of cases, 88% of deaths) occurring in developing countries. Approximately 90% of anal cancers and a smaller subset (< 50%) of other cancers (oropharyngeal, penile, vaginal, vulvar) are also attributed to HPV. In total, HPV accounts for 5.2% of the worldwide cancer burden. HPVs 16 and 18 are responsible for 70% of cervical cancer cases and, especially HPV 16, for a large proportion of other cancers. Prophylactic vaccination targeting these genotypes is therefore expected to have a major impact on the burden of cervical cancer as well as that of other HPV-related cancers. Over the past 50 years, organized or opportunistic screening with Papanicolaou (Pap) cytology has led to major reductions in cervical cancer in most developed countries. However, due to lack of resources or inadequate infrastructure, many countries have failed to reduce cervical cancer mortality through screening. HPV DNA testing recently emerged as a likely candidate to replace Pap cytology for primary screening. It is less prone to human error and more sensitive than Pap in detecting high-grade cervical lesions. For countries with national vaccination programs, HPV testing may also serve as a low cost strategy to monitor long term vaccine efficacy. Introduction of well organized vaccination and screening programs should be a priority for all countries. Increased support from donors is needed to support this cause.

Introduction

Human papillomavirus (HPV) is currently one of the most common sexually transmitted infections worldwide (Baseman and Koutsky, 2005, Dunne et al., 2007, Ebrahim et al., 2005). Most individuals (~ 75%) who engage in sexual activity will become infected with HPV at some point during their lifetime (Baseman and Koutsky, 2005, Koutsky et al., 1988). For the vast majority these infections will be asymptomatic and clear within 1–2 years (Franco et al., 1999, Hildesheim et al., 1994, Ho et al., 1998, Molano et al., 2003, Moscicki et al., 1998, Richardson et al., 2003); however, a substantial increase in risk for cervical cancer exists for women who develop persistent infection with high-oncogenic HPV types (HR-HPV) (Ho et al., 1995, Liaw et al., 1999, Remmink et al., 1995, Ylitalo et al., 2000). Infection with low-oncogenic risk HPV types (LR-HPV) is also responsible for considerable morbidity associated with benign lesions known as acuminate condylomata (genital warts) as well as a large proportion of low grade squamous intraepithelial cervical lesions. In this review we discuss the burden of HPV infection and related diseases, mainly focusing on cervical cancer and opportunities for prevention.

Section snippets

Epidemiology of HPV infection

According to a recent meta-analysis that included data from more than 1 million women in 59 countries, the prevalence of genital HPV infection among those with normal cytology ranges from 1.6% to 41.9% (Bruni et al., 2010). Higher HPV prevalence was observed in African and Latin American regions in comparison to European, North American and Asian regions. The estimated average global prevalence of HPV in this particular study was 11.7%, which is similar to previous reports focusing on women (

Sexual activity and other risk factors for HPV infection

HPV is highly sexually transmissible in both genders (Burchell et al., 2006, Castellsague et al., 2003, Marrazzo et al., 2001). Epidemiologic studies have consistently reported markers of sexual activity, including number of recent/lifetime sexual partners and age at sexual debut to be among the most important risk factors for HPV infection (Ho et al., 1998, Moscicki et al., 2001, Richardson et al., 2000, Winer et al., 2003). Although age at sexual debut is often strongly associated with other

HPV infection and risk of cervical cancer and other diseases

In 1995, the International Agency for Research on Cancer (IARC) first classified HPV types 16 and 18 as carcinogenic to humans, but based on more recent evidence, the list of carcinogenic HPV types has been expanded to include a total of 13 mucosotropic anogenital HPV types as being definite or probable carcinogens (grade 1 or 2a) based on their frequent association with invasive cervical cancer (ICC) and cervical intraepithelial neoplasia (CIN) (see Table 1 for HR-HPVs) (Schiffman et al., 2009

Persistent HPV infection and cervical carcinogenesis

Most cervical HPV infections clear spontaneously without ever causing lesions. Only a small proportion of infections (10–30%) will persist beyond 1 or 2 years. Data from cohort studies indicate that the average length of infection is between 4 and 20 months, with HR-HPV types lasting longer than LR-HPV types (Franco et al., 1999, Hildesheim et al., 1994, Ho et al., 1998, Molano et al., 2003, Moscicki et al., 1998, Richardson et al., 2003). Numerous cohort studies have confirmed that risk of CIN

Burden of cancer caused by HPV: cervix and other sites

After breast and colorectal cancer, cervical cancer is the 3rd leading cancer site worldwide irrespective of gender and second among women. In 2008, there were an estimated 530,000 cases and 270,000 deaths attributed to ICC, with 86% of cases and 88% of deaths occurring in developing countries (Arbyn et al., in press). In these developing countries, the age-standardized incidence rate (ASIR) and age-standardized mortality rate (ASMR) were 18 and 10 per 100,000 women, respectively; whereas in

Current and future opportunities for prevention

The discovery of HPV infection as a necessary cause of cervical cancer has created many new paths for prevention. The most promising strategies include screening for infection with HR-HPV types and immunization to prevent infection with HR-HPV types.

Pap cytology screening, which has over 50 years of history in medicine, is considered the primary reason we have witnessed a major reduction in cervical cancer mortality in most high-income countries (Arbyn et al., 2009, Jemal et al., 2010). But in

Prevention strategies in developed and developing countries

Despite breakthroughs in screening and prevention, cervical cancer remains an important cause of cancer death globally, especially in developing countries where the majority of the burden lies. Although prophylactic vaccination is expected to substantially reduce HPV-associated morbidity and mortality, it currently remains too expensive for introduction in most resource-poor countries (Goldie et al., 2008, Anon, 2011). Rwanda recently became the first African country to introduce a national

Conflict of interest statement

ELF has served as consultant to Merck, Roche and Gen-Probe, and received unconditional grants from Merck in support of one of his studies. The other authors have no specific associations with industry to report.

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