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