HPV infection is a common viral infection worldwide, with nearly 291 million HPV-positive women predicted to be in the world in 2007 [1, 2]. Studies have found geographical and population-based differences in global HPV infection rates [2, 3]. A meta-analysis that included 194 studies from around the world found a crude HPV prevalence of 7.2% (95% CI: 7.1%-7.2%) and estimated that the global prevalence of HPV infection among women with normal cervical cytology was approximately 11.7% (95% CI: 11.6%-11.7%) after adjusting factors such as regional distribution, mean age of the women, year of the study, and the study methodology. The highest prevalence of HPV infection was found in the Caribbean (35.4%, 95% CI: 29.0%-42.2%), East Africa (33.6%, 95% CI: 30.2-37.1%), sub-Saharan Africa (24.0%, 95% CI: 23.1%-25.0%) and Eastern Europe (21.4%, 95% CI: 20.1-22.7%) [4]. Regional differences are associated with the economic development level of countries and regions, with more developed high-income countries or regions (e.g., North America, West Asia) having lower HPV infection rates than other less developed countries or regions (Figure 1).
Figure 1. HPV prevalence in women with normal cervical cytology
Among women with normal cervical cytology, the prevalence of HPV infection is highest in the age group <25 years and decreases with age. However, the trend of HPV prevalence with age is not consistent across regions [5]. As shown in Figure 2, in Africa, there is again a trend of increasing HPV prevalence among women after middle age, and a second small peak in prevalence is also observed in Asia and Americas.
Figure 2. Crude age-specific HPV prevalence (%) and 95%CI in women with normal cervical cytology in the World and its regions.
Studies have also found that the HPV infection rate rises with the increasing severity of cervical lesions. A review and meta-analysis that included 423 studies found that the HPV infection rate increased significantly as the grade of the lesion increased [6]. This study found that the HPV-positive rate was 12% in women with normal cervical cells, 52.5% in women with atypical squamous epithelial cell changes of no clear significance (ASCUS) as a result of cervical cytology, 76% in women with low-grade squamous intraepithelial lesions (LSIL), and 85% in women with high-grade squamous intraepithelial lesions (HSIL).
Globally, data from all continents show that HPV16 infection has the highest prevalence, while HPV18 is the second most common type. The distribution of HPV types also varies geographically [7]. For example, in Asia, HPV33 is a more common type, and the prevalence of HPV52 and HPV58 is relatively low. The prevalence of high-risk HPV16/18 infections increases with the degree of disease [5]. (Figure 3)
Figure 3 Comparison of the 10 most frequent HPV oncogenic types among women with normal cytology and all levels of cervical lesions (left panel) and invasive cervical cancer (right panel) in developed and less developed regions of the world
In the cytologically normal population, the top ten most common HPV infection types worldwide were, in order, HPV16 (2.8%), HPV52 (1.5%), HPV31 (1.2%), HPV53 (1.2%), HPV18 (1.1%), HPV51 (1.1%), HPV58 (1.0%), and HPV39 (0.9%), HPV66 (0.9%), and HPV70 (0.8%). Among those with precancerous lesions, the HPV infection type changed as the degree of cervical precancerous lesions increased. Common types of HPV infection among patients with low-grade squamous intraepithelial lesions (ISIL) worldwide were HPV16 (19.3%), HPV52 (8.9%), HPV51 (8.8%), HPV31 (7.7%), HPV53 (7.3%), HPV66 (6.9%), HPV58 (6.7%), HPV56 (6.6%) , HPV18 (6.5%), and HPV39 (5.3%). The common types of HPV infection among women with high-grade squamous intraepithelial lesions (HSIL) were HPV16 (45.1%), HPV52 (11.0%), HPV31 (10.4%), HPV58 (8.1%), HPV33 (7.3%), HPV18 (6.8%), HPV51 (5.7%), HPV53 (3.5%), HPV39 (3.3%), and HPV35 (3.3%); whereas among patients with cervical cancer, the order was HPV16 (55.2%), HPV18 (14.2%), HPV45 (5.0%), HPV33 (4.2%), HPV58 (3.9%), HPV31 (3.5%), HPV52 (3.5%), HPV35 ( 1.7%), HPV39 (1.5%), and HPV59 (1.4%) (Figure 3).
HPV infection and related diseases also impose a huge economic burden on the healthcare system and society. Table 1 summarizes the economic burden caused by HPV-related diseases in selected countries, with the direct economic burden ranging from 47.16 million to 1.8 billion RMB [8].
Table 1. Economic burden of HPV-related diseases in selected countries
| Country | Related Diseases | Research Perspectives | Total economic burden (¥10K) | Direct economic burden (¥ 10K) | Primary data sources |
| Korea, 2018 | Genital warts | Social perspective | 6,492 | 4,716 | Health insurance review and assessment data |
| Sweden, 2017 | Cervical cancer, genital warts | Social perspective | 73,637 | 24,441 | National Board of Health and Welfare |
| Japan, 2017 | Cervical cancer | healthcare system | – | 112,819 | Evidence-based medicine provider database |
| Swaziland, 2017 | Cervical lesions, genital warts | healthcare system | – | 10,645 | Swaziland National Cancer Registry |
| Singapore, 2012 | Cervical cancer, genital warts | healthcare system | – | 40,786 | Cancer Registry Singapore |
| Italy, 2012 | Cervical cancer, cervical atypical hyperplasia, etc. | healthcare system | – | 415,421 | MEDLINE, EMBASE database |
| France, 2011 | Cervical cancer, vaginal cancer, etc. | healthcare system | – | 188,378 | French National Hospital Database |
(Table source: Yike Li, Siyi Chen, Xiaofen Huang, Ya Fang, & Qinjian Zhao. (2018). Clinical utility of human papillomavirus vaccine and its economics. Modern Preventive Medicine, 45(15).)
Content Reviewer: Kelly Hunter, Zhangyang Pan
References:
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- Bruni L, Diaz M, Castellsagué M, Ferrer E, Bosch FX, de Sanjosé S: Cervical human papillomavirus prevalence in 5 continents: meta-analysis of 1 million women with normal cytological findings. Journal of Infectious Diseases 2010, 202(12):1789-1799.
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- Li YK, Chen SY, Huang SF, Fang Y, Zhao QJ: Clinical utility of human papillomavirus vaccine and its economics. Modern Preventive Medicine 2018, 45 (15).
