Data on the geographic distribution of HPV type in HSIL and ICC are crucial for estimating the impact of HPV vaccines on cervical cancer and cervical screening programs. 
Epidemiological studies employing a variety of HPV typing protocols have been aggregated in some meta-analyses. However, the number of samples from LA&C considered in these studies was relatively low.
This review brings representative estimations of HPV type distribution from the LA&C region. Since multiple HPV genotyping techniques have been included, varying sensitivities of the techniques considered might impact the HPV type-specific prevalence reported 
. Currently, identification of specific HPV types in biological specimens is preferentially done by PCR-based methods due to its higher sensitivity; in this study, however, hybridization techniques without PCR amplification (membrane and in situ hybridization) were also included in order to incorporate the largest number of HSIL and ICC cases, and to increase the representativeness of the data. Nevertheless, only 6% of studies -the oldest ones- used non-PCR-based techniques.
In 2003, Smith et al. 
updated a meta-analysis of over 10,000 cases published 
. It retrieved 1,427 cancer cases and 833 HSIL cases from 13 countries in the LA&C region; the prevalence of HPV 16/18 in cervical cancer for South/Central America was 65%. Muñoz et al., in 2004, included 1,084 cervical cancer cases from Central/South America and found an HPV16/18 prevalence of 69%. 
. Later, Li et al have published a worldwide meta-analysis of HPV type-specific including a total of 30,848 cervical cancers. It included 3,010 cancer cases from 15 countries of LA&C; in this region for 1990–2010, HPV16 and HPV18 were the first and second most common types, respectively (54% and 15% respectively); being the third to eighth most common types HPVs 31, 45, 33, 58, 52 and 35. 
. The present systematic tripled the number HSIL cases included in the previous reports of Clifford et al. 
and Smith et al. 
. Overall, 55% of HSIL cases harbored HPV 16/18, confirming that HPV type distribution in HSIL does not entirely match that of ICC. HPV types 16, 18 and 45 are less common in HSIL than in ICC, whereas other HPV types are more frequent (particularly, HPV58, the third-most prevalent type in HSIL). These differences emphasize the importance of HPV type in the risk of progression to cancer, even from HSIL. The proportions of HSIL cases attributable to both HPV16 and HPV 18 in this study were higher than those in previous meta-analyses 
, which estimated 48% for the region. Our prevalence HPV 16/18 rate is similar to Europe (57.6%) and North America (55.1%), according to the study published by Smith et al. 
Data on ICC has greatly enriched previous reports; we increased the number of Latin American cases included from 3,010 considered by the last published meta-analysis 
to 5,542 in our study. Regarding ICC cases, 53.2% harbored HPV 16 and 13.2% HPV18, confirming that they are the first- and second-most prevalent types, respectively, which agrees with data previously obtained on other continents and worldwide. The next five-most common types, (HPV 31, 58, 33, 45, and 52) added 22.6% of cases. The proportions of cases attributable to HPV16/18 in this study were similar to previous meta-analyses 
, which estimated nearly 65% for the region. Our findings corroborate that in LA&C the HPV16/18 prevalence of ICC is similar to that of Asia (66.9%) and lower than that of Africa (70%), Europe (73.8%) and North America (76.4%), according Smith et al. 
Some intra-regional variations of the most common HPV types have been observed, although these apparent differences may happen simply by random fluctuation and/or a lack of sample representativeness of certain countries. For ICC, Mexico, Central America and the Caribbean showed a slightly lower HPV16/18 prevalence than South America (64.2% vs. 67.3% respectively). Particularly, Argentina shows the highest prevalence rate for HPV16/18 in both HSIL (65.4%) and ICC (77.1%). It is interesting to point out that the 12 Argentine studies incorporated samples from women of different provinces of the country, including aboriginal communities (Quechua 
and Guarani 
populations), revealing similar HPV16/18 prevalence data.
In 11.6% of HSIL and 7.5% of ICC, HPV detection resulted positive, but the viral type could not be identified (“other type”); these cases most likely represent the failed detection of known types (almost certainly different than HPV 16 and 18) rather than infections of yet-undiscovered types.
In this review, multiple-type HPV infections were detected in 16.8% of HSIL and 12.6% of ICC, although the frequency of multiple infections depends largely on the number of HPV types tested for within a given study. The attribution of ICC etiology to HPV types is increasingly complicated by the rising prevalence of multiple co-existing types. It was suggested that infections with multiple HPV types seem to act synergistically in cervical carcinogenesis 
, and it was also associated with poor response and with reduced survival in cervical cancer patients. 
. However, other study indicates that despite the presence of many viruses infecting the same anatomical site, only one genotype would be responsible for the disease 
HPV18 and 16 had the highest ICC
HSIL prevalence ratio in our studies, as found in Smith et al. meta-analysis 
. Conversely, HPV11, 56, 6, 68 and 58, were each 2 to 3-fold more prevalent in HSIL than in ICC. These lowest ratios were observed for many different types and lower than reported 
As more data is accumulated, it is supportive to observe that HPV16/18 accounts for two-thirds of ICC in LA&C. The proportion of ICC cases potentially averted by the current approved vaccines may be even higher than the aforementioned one if cross-protection against non-vaccine high-risk HPV types (like HPV31 and 45) is found to be clinically effective in reducing the incidence of ICC and HSIL caused by these genotypes. The information given by this work would be also useful in LA&C for the evaluation of polyvalent vaccines (currently in development) for the prevention of ICC associated to more than eight or nine high-risk HPV types.
Limitations of our meta-analysis include the cross-sectional design of the included studies and their inherent risk of bias, lack of representativeness, the HPV type-specific prevalence variation and HPV type-specific sensitivity of different PCR protocols 
. There is evidence of considerable heterogeneity between studies. Heterogeneity could not be ruled out even by the pre-designed subgroup analysis: by country, region, and GNI World Bank classification. However inconsistencies might be explained by variations in the population and methods utilized. To address this issue we chose the random effect model meta-analysis to combine data in order to obtain conservative (wider) confidence intervals, which may result more informative than central estimates. In addition 61% of the patients included in the meta-analysis came from only three countries (Argentina, Brazil and Mexico) and one should be cautious when extrapolating our summary results to the entire region. Further, many studies did not type for a broad range of HPV types, and cyto-histological diagnoses across studies were not standardized. The poor infrastructure of research in molecular biology in many countries highlights the need to consider strategic alliances and promoting regional research consortia on the topic of HPV. In this way, according to the World Health Organization HPV Laboratory Network (WHO HPV LabNet) guidelines, the establishment of a Regional HPV LabNet would be extremely useful 
. This is initiative would support the laboratory standardization and quality assurance of HPV typing methods to promote international comparability of results, promoting an appropriate vaccine introduction and virological surveillance in the vaccine era.
Although information on the histological type of ICC was collected, its discrimination was not always clear and the data came mostly from SCC. For this reason we presented only global data of ICC.
This study is the broadest summary of HPV type distribution in HSIL and ICC in LA&C to date, and it has included the majority of American countries which have the highest cervical cancer burdens in the region and worldwide. The presented information may be of importance for local decision makers to consider the cervical cancer prevention as a whole, taking into account the relevance of vaccination and updating screening strategies using type-specific high-risk HPV-DNA-based tests. This work comes available at the time some Latin American and Caribbean countries are evaluating the HPV vaccine introduction in their National Vaccination Schedules, in the frame of the Pan American Health Organization purchase using revolving fund, which makes vaccines affordable. Continued surveillance of HPV types in HSIL and ICC as HPV vaccines are introduced would be useful, to assess the potential for changing type-specific HPV prevalence in the post-vaccination era in Latin America.