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Worldwide prevalence and genotype distribution of cervical human papillomavirus DNA in women with normal cytology: a meta-analysis

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Summary

We set out to estimate the age and genotype-specific prevalence of cervical human papillomavirus (HPV) DNA in women with normal cervical cytology worldwide by meta-analysis of a systematic literature review. Reports on HPV prevalence published between January, 1995, and January, 2005, were retrieved. To be included, studies required information on cervical cytology, plus detailed descriptions of study populations, methods used to collect cervical samples, and assays used for HPV DNA detection and typing. Final analyses included 78 studies that could be separated into women with normal cytology, and of which subsets of 44 and 48 studies had data on age and type-specific HPV prevalence, respectively. Overall HPV prevalence in 157 879 women with normal cervical cytology was estimated to be 10·4% (95% CI 10·2–10·7). Corresponding estimates by region were Africa 22·1% (20·9–23·4), Central America and Mexico 20·4% (19·3–21·4), northern America 11·3% (10·6–12·1), Europe 8·1% (7·8–8·4), and Asia 8·0% (7·5–8·4). In all world regions, HPV prevalence was highest in women younger than 35 years of age, decreasing in women of older age. In Africa, the Americas, and Europe, a clear second peak of HPV prevalence was observed in women aged 45 years or older. On the basis of these estimates, around 291 million women worldwide are carriers of HPV DNA, of whom 32% are infected with HPV16 or HPV18, or both. The HPV types most commonly detected are similar to those most commonly described in pre-neoplastic and cancer cases, although the relative contribution of HPV16 and HPV18 is substantially lower in cytologically normal women.

Introduction

Infection by certain types of human papillomavirus (HPV) is recognised as a causal and necessary factor for cervical cancer.1, 2, 3 Cervical cancer represents the second most common malignancy in women around the world and contributes to 9·8% of all female cancers.4 Other tumours related to HPV, such as anal, vaginal, vulvar, penile, and oropharyngeal, represent an additional 0·7% of all cancer sites in both men and women, so that HPV is estimated to be responsible for 5·2% of all cancers worldwide.5 A cross-sectional evaluation of the HPV DNA prevalence in 13 countries estimated that 6·6% of women in the age-range 15–74 years with normal cytology are carriers of HPV DNA, with marked variation within and between world regions (range 1·4–25·6%).6 Therefore, HPV can be considered as the most common known sexually transmitted agent worldwide.

To allow further comparisons of prevalence, type, and age-distribution of HPV across world regions, published data from female populations participating in screening programmes or epidemiological studies were retrieved and pooled. Statistical models were built to adjust for confounding variables and to standardise results to allow comparability of HPV prevalence estimates worldwide.

Section snippets

Identification and eligibility of relevant studies

A systematic Medline search was done to identify all reports on HPV prevalence published from January, 1995, to January, 2005, using combinations of the following index terms: “Papovaviridae”, “Papillomavirus (human)”, “Cervix neoplasms (epidemiology OR virology OR prevention and control)”, “epidemiology”, “prevalence”, “DNA probes (HPV)”, “polymerase chain reaction”, “enzyme-linked immunosorbent assay”, “women/female”, and “population”. Relevant additional references cited in retrieved

Results

The table shows crude and adjusted HPV prevalence estimates in 157 879 women with normal cytology, stratified by 15 world regions. The largest sample consisted of European studies (44·4% of all study women), followed by studies from the Americas (16·3% and 9·2% for northern and Central/South America, respectively). Studies from Asia contributed 26·0% of all study participants, of whom half were from south-central Asia (Indian subcontinent). African studies contributed 3·9% of all study women.

Discussion

This large meta-analysis of 157 879 women with normal cytology derived from 78 published studies worldwide allowed us to produce the most precise, comprehensive, and comparable estimates of HPV prevalence to date. The results estimate that at any given point in time, 10·4% of women worldwide were positive for cervical HPV DNA. Prevalence of HPV was higher in less developed countries (15·5%) than more developed countries (10·0%), and was highest in women younger than 25 years old (16·9%),

Age-related prevalence

This meta-analysis confirms that HPV infection is most common in women younger than 25 years of age. However, a second peak of HPV prevalence is seen in women aged 45 years or older in all regions with the exception of Asia. The pattern was not consistent, however, because the turning point from a downward trend to an upward trend was observed after 54 years of age in Africa and Europe, but after 44 years of age in estimates from the Americas. This age-specific phenomenon observed in older

Search strategy and selection criteria

These are described in detail in the Methods section on page 453.

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