Of HPV-Infected Women With Normal Smears, Most Have High-Risk Varieties
The proportion of women who do not have cancerous or precancerous changes of their cervix but who are infected with human papillomavirus (HPV) varies widely across world regions—from 5% in Europe to 26% in Sub-Saharan Africa, according to a pooled analysis of population-based surveys.1 Sub-Saharan Africa had the highest prevalence of infection with HPV16, a type associated with a high risk of cervical cancer. However, compared with HPV-positive women in Sub-Saharan Africa, those in Europe and South America were more likely to be infected with HPV16 and less likely to be infected with other high-risk types or with low-risk types.
In the surveys, conducted between 1993 and 2003, women were randomly selected from the general populations of 13 areas in 11 countries (Nigeria, India, Vietnam, Thailand, Korea, Colombia, Argentina, Chile, the Netherlands, Italy and Spain). Cervical cells collected during pelvic examinations were used to prepare Pap or liquid-based smears, and were tested by polymerase chain reaction and enzyme immunoassay to assess the presence and types of HPV. HPV prevalence was standardized by age using the world standard population as the reference. Prevalence was estimated for each of the four regions represented—Asia, Europe, South America and Sub-Saharan Africa (Nigeria)—by pooling the results for the sampled areas within each region.
Analyses were based on 15,613 sexually active, nonpregnant women aged 15-74 who had normal cervical smears. Overall, slightly more than 9% of women tested positive for HPV; 7% had only one type of the virus and 3% had multiple types. By area, the age-standardized prevalence of HPV infection varied from about 1% in Spain to 26% in Nigeria. By region, prevalence varied from 5% in Europe to 26% in Sub-Saharan Africa.
Overall, the majority (67%) of HPV-positive women with normal smears were infected with at least one of the viral types associated with a high risk of progression to cervical cancer; 28% were infected with low-risk types only and 3% with unidentifiable types. Of the 36 viral types studied, the single most common was HPV16, the type most strongly linked to cervical cancer; its prevalence among all women in the population was highest (3.2%) in Sub-Saharan Africa, intermediate (2.9%) in South America and lowest (1.5-1.7%) in Europe and Asia.
The distribution of HPV types varied by region. In three regions—Asia, Europe and South America—the proportion of HPV16 infections among all HPV infections in women with normal smears was twice that of any other high-risk type, but in Sub-Saharan Africa, the proportion of HPV16 equaled that of the high-risk type HPV35. In age-adjusted analyses, HPV-positive women in Europe and South America had significantly higher odds of being infected with HPV16 than did their Sub-Saharan African counterparts (odds ratios, 2.6 and 1.9, respectively); those in Europe had lower odds of infection with other high-risk types (0.6) or with low-risk types (0.4).
The likelihood of infection with five other high-risk types among HPV-positive women also varied significantly across regions. Compared with women in Sub-Saharan Africa, those in Asia were less likely to be infected with HPV45 (odds ratio, 0.3) but more likely to be infected with HPV33 (3.5), and those in in Asia and South America were less likely to be infected with HPV35 (0.3).
The researchers speculate that the variations observed in this study both within and across world regions stems from a complex interaction of factors, including characteristics of each viral type, genetic influences on immunity and community levels of health conditions that compromise immune function, such as chronic cervical inflammation, malnutrition and HIV. They recommend, therefore, that "heterogeneity in HPV type distribution among women from different populations should be taken into account when developing screening tests for the virus and predicting the effect of vaccines on the incidence of infection." —S. London
1. Clifford GM et al., Worldwide distribution of human papillomavirus types in cytologically normal women in the International Agency for Research on Cancer HPV prevalence surveys: a pooled analysis, Lancet, 2005, 366(9490):991-998.