Data on human papillomavirus (HPV) type distribution in invasive and pre-invasive cervical cancer is essential to predict the future impact of HPV16/18 vaccines and HPV-based screening tests. A meta-analyses of HPV type distribution in invasive cervical cancer (ICC) and high-grade squamous intraepithelial lesions (HSIL) identified a total of 14,595 and 7,094 cases, respectively. In ICC, HPV16 was the most common, and HPV18 the second most common, type in all continents. Combined HPV16/18 prevalence among ICC cases was slightly higher in Europe, North America and Australia (74-77%) than in Africa, Asia and South/Central America (65-70%). The next most common HPV types were the same in each continent, namely HPV31, 33, 35, 45, 52 and 58, although their relative importance differed somewhat by region. HPV18 was significantly more prevalent in adeno/adenosquamous carcinoma than in squamous cell carcinoma, with the reverse being true for HPV16, 31, 33, 52 and 58. Among HSIL cases, HPV16/18 prevalence was 52%. However, HPV 16, 18 and 45 were significantly under-represented, and other highrisk HPV types significantly over-represented in HSIL compared to ICC, suggesting differences in type-specific risks for progression. Data on HPV-typed ICC and HSIL cases were particularly scarce from large regions of Africa and Central Asia. ' 2007 Wiley-Liss, Inc.Key words: human papillomavirus; genotype; cervical cancer; highgrade squamous intraepithelial lesions; meta-analysis; epidemiology Data on human papillomavirus (HPV) type distribution in women with invasive cervical cancer (ICC) and its precursor lesions are essential to predict the potential worldwide impact of new prophylactic vaccines against HPV16/18, 1,2 as well as to determine priorities for the inclusion of HPV types in future HPV vaccines and HPV-based screening tests.A standardised pooled analysis of 3,607 ICC cases 3 and a wider meta-analysis of 10,058 ICC cases 4 both confirmed that a majority of worldwide ICC cases are associated with HPV16/18. They also suggested some geographical variation in the importance of specific HPV types, 3,4 although data were limited or missing from many regions in Africa and Asia.A further meta-analysis in 4,338 high-grade squamous intraepithelial lesions (HSIL) showed that the most common HPV types in HSIL were broadly similar, but not identical, to those in ICC. 5 The purpose of the present publication is to update previous meta-analyses of HPV type distribution in ICC and HSIL with studies published between January 2002 and January 2006, including many from previously under-studied regions, and to identify remaining worldwide epidemiological data gaps prior to HPV vaccine implementation. Material and methodsThe detailed methods used for this meta-analysis of type-specific HPV prevalence have been reported previously, and are similar for both ICC and HSIL. 4,5 In brief, Medline was employed to search for citations published from January 2002 to January 2006 using the following MeSH terms: ''cervical cancer'', ''cervical intraepit...

This study investigated regional variations in the contribution made by different human papilloma (HPV) types to invasive cervical cancer (ICC). A total of 85 studies using polymerase chain reaction to estimate HPV prevalence in ICC were identified. Data on HPV prevalence were extracted separately for squamous cell carcinoma (SCC) and for adeno-and adenosquamous-carcinoma (ADC). A total of 10 058 cases (8550 SCC, 1508 ADC) were included in pooled analyses. The most common HPV types in ICC were, in order of decreasing prevalence, HPV16, 18, 45, 31, 33, 58, 52, 35, 59, 56, 6, 51, 68, 39, 82, 73, 66 and 70. In SCC, HPV16 was the predominant type (46 -63%) followed by HPV18 (10 -14%), 45 (2 -8%), 31 (2 -7%) and 33 (3 -5%) in all regions except Asia, where HPV types 58 (6%) and 52 (4%) were more frequently identified. In ADC, HPV prevalence was significantly lower (76.4%) than in SCC (87.3%), and HPV18 was the predominant type in every region (37 -41%), followed by 16 (26 -36%) and 45 (5 -7%). The overall detection of HPV DNA was similar in different regions (83 -89%). A majority of ICC was associated with HPV16 or 18 in all regions, but approximately a quarter of all ICC cases were associated with one of 16 other HPV types, their distribution varying by region. British Journal of Cancer (2003) Epidemiological studies have clearly established human papillomavirus (HPV) infection as the central cause of invasive cervical cancer (ICC). This is the second most common cancer among women worldwide and the most common female cancer in large areas of the developing world where an estimated 80% of new cases arise (Parkin et al, 1999). Studies in 22 countries, coordinated by the International Agency for Research on Cancer (IARC), identified HPV DNA in almost all (99.7%) (of about 1000) cases of cervical cancer (Walboomers et al, 1999).Approximately 40 distinct HPV types are known to infect the genital tract and epidemiological studies to date suggest that at least 14 of these, called oncogenic or high-risk (HR) types, are significantly associated with progression to ICC (Bosch et al, 1995). Most of these HR types are phylogenetically related to either HPV16 (31, 33, 35, 52 and 58) or HPV18 (39, 45, 59 and 68) (Chan et al, 1995). Limited evidence suggests that their distribution may vary by region (Bosch et al, 1995).HPV vaccines hold great promise to reduce the global burden of ICC any potential vaccine be multivalent since prior infection with one type does not appear to decrease the risk of infection by another HPV type (Koutsky et al, 2002;Combita et al, 2002; Liaw et al, 2001). In this however, to collate all relevant published data to identify the most prevalent HPV types associated with ICC worldwide and within five geographic regions. MATERIALS AND METHODS Study selectionSource material was selected from citations listed in Medline and ISI Current Contents databases and from references cited in the selected papers. Key search terms included: cervical cancer, HPV, human, female, and polymerase chain reaction (PCR). ...

Information on age- and sex-specific prevalence of herpes simplex virus (HSV) types 2 and 1 infections is essential to optimize genital herpes control strategies, which increase in importance because accumulating data indicate that HSV-2 infection may increase acquisition and transmission of human immunodeficiency virus. This review summarizes data from peer-reviewed publications of type-specific HSV seroepidemiologic surveys. HSV-2 prevalence is, in general, highest in Africa and the Americas, lower in western and southern Europe than in northern Europe and North America, and lowest in Asia. HSV-2 and -1 prevalence, overall and by age, varies markedly by country, region within country, and population subgroup. Age-specific HSV-2 prevalence is usually higher in women than men and in populations with higher risk sexual behavior. HSV-2 prevalence has increased in the United States but national data from other countries are unavailable. HSV-1 infection is acquired during childhood and adolescence and is markedly more widespread than HSV-2 infection. Further studies are needed in many geographic areas.

Objectives To assess and summarize the published literature on the extent to which bacterial vaginosis (BV) may increase the risk of HIV acquisition. Design Meta-analysis of published studies. Methods MEDLINE and other electronic databases were systematically searched for eligible publications. The association between BV and incident HIV was separately analyzed from that between BV and prevalent HIV. The latter were further analyzed stratified by BV diagnostic method, HIV risk profile of the study population and whether or not adjusted estimates were presented. Results Twenty-three eligible publications were identified, including a total of 30,739 women. BV was associated with an increased risk of HIV acquisition in HIV-incidence studies (relative risk = 1.6, 95% CI: 1.2, 2.1). All but one of 21 HIV-prevalence studies reported estimates above the null. The latter results were heterogeneous and showed some evidence of funnel plot asymmetry, precluding the estimation of a single summary measure. The association between BV and HIV in prevalence studies appeared stronger for women without high-risk sexual behavior. Conclusions BV was consistently associated with an increased risk of HIV infection. High BV prevalence may result in a high number of HIV infections being attributable to BV. More prospective studies are needed to accurately evaluate the role of BV in HIV acquisition in low versus high risk women. Furthermore, randomized clinical trials may be worth considering to determine the effect of BV control measures on HIV acquisition.

Particular types of human papillomavirus (HPV) infection may preferentially progress from high-grade squamous intraepithelial lesions (HSIL) to squamous cell carcinoma of the cervix (SCC). We performed a meta-analysis of published data to compare HPV type distribution in HSIL and SCC. HPV16, 18 and 45 were each more prevalent in SCC than HSIL, whereas the reverse was true for other oncogenic types including HPV31, 33, 52 and 58. These data suggest that HSILs infected with HPV16, 18 and 45 preferentially progress to SCC. This may have implications for follow-up protocols of future HPV-based cervical cancer screening programmes and for HPV vaccine trials. (Walboomers et al, 1999). However, only a fraction of precancerous lesions progress to ICC. A strong candidate factor for differential progression is HPV type (Lorincz et al, 1992).Identifying HPV types that preferentially progress from highgrade squamous intraepithelial lesions (HSIL) to ICC has implications not only for follow-up protocols in ICC screening programmes, but also for prophylactic type-specific HPV vaccine trials. For ethical reasons, final outcome measures in such trials will be the prevention of HSIL. However, it is important to know whether the HPV type distribution in HSIL is representative of those that go on to cause cancer.Articles presenting HPV type-specific prevalence data were identified from Medline. Studies had to include at least 20 cases of squamous cell or histologically unspecified cervical cancer (Clifford et al, 2002) and/or 20 histologically verified cases of HSIL. In this study, HSIL refers both to lesions classified by the Bethesda system, that is, CIN2/3, and those classified separately as CIN2 and CIN3. Studies had to use polymerase chain reaction (PCR)-based assays to identify HPV, and to present prevalence of at least one type other than HPV6, 11, 16 or 18 (Clifford et al, 2002).This report includes 8594 squamous cell carcinoma of the cervix (SCC) cases (including 2725 of unspecified histology), as previously reported in Clifford et al (2002), and 4338 HSIL cases (1733 reported as CIN2/3, 1824 as CIN3, 729 as CIN2 and 52 as cervical carcinoma in situ)(detailed information on the HSIL studies is reported in the Appendix). Compared to SCC, cases of HSIL were more likely to be from (i) Europe and South/Central America rather than other regions, (ii) studies that detected HPV from exfoliated cells rather than biopsy specimens and (iii) studies that used 'broad'-spectrum (MY09/11, GP5 þ /6 þ and SPF10) rather than other PCR primers (Table 1).Type-specific prevalence is presented for the 14 most common high-risk (HR) types identified in SCC ( Table 2). As not all studies tested for all 14 types, sample size varies between type-specific analyses. Type-specific prevalence is expressed as a percentage of all cases tested for HPV, and thus represents the prevalence in either single or multiple infections.Overall, HPV prevalence was slightly higher in SCC cases (87.6%) than HSIL (84.2%) (SCC : HSIL ratio 1.04, 95% CI 1.03 -1.06) ( T...

HPV appears to be the key risk factor for cervical adenocarcinoma. HPV testing in primary screening using current mixtures of HPV types and HPV vaccination against main HPV types should reduce the incidence of this cancer worldwide.

Low-grade squamous intraepithelial lesions (LSIL) associated with certain human papillomavirus (HPV) genotypes may preferentially progress to cervical cancer. HPV genotyping may thus have the potential to improve the effectiveness of screening programs and to reduce overtreatment. LSIL cases (n = 8,308) from 55 published studies were included in a meta-analysis. HPV genotype distribution was assessed by geographic region and in comparison with published data on cervical squamous cell carcinoma (SCC). HPV detection in LSIL was 80% in North America but less than 70% in other regions, most likely reflecting regional differences in LSIL diagnosis. Among 5,910 HPVpositive LSILs, HPV16 was the most common genotype (26.3%) followed by HPV31 (11.5%), HPV51 (10.6%), and HPV53 (10.2%). HPV-positive LSILs from Africa were 2-fold less likely to be infected with HPV16 than those in Europe, and HPV-positive LSILs from North America were more likely to be infected with HPV18 than those from Europe or South/Central America. Interpretation for rarer genotypes was hampered by variation in HPV testing methodology. SCC/LSIL prevalence ratios indicated that HPV16 was 2-fold and HPV18 was 1.5-fold more common in SCC than in HPV-positive LSIL, thus appearing more likely to progress than other high-risk genotypes (SCC/LSIL prevalence ratios between 0.05 and 0.85). HPV53 and HPV66 showed SCC/LSIL ratios of 0.02 and 0.01, respectively. HPV genotype distribution in LSIL differs from that in cervical cancer, highlighting the importance of HPV genotype in the risk of progression from LSIL to malignancy. Some regional differences in the relative importance of HPV genotypes in LSIL were noted.

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