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Human papillomavirus (HPV) infection and cervical squamous intraepithelial lesions (SILs) were studied in 379 high-risk women. Human papillomavirus DNA was detected in 238 of 360 (66.1%) of the beta-globin-positive cervical samples, and 467 HPV isolates belonging to 35 types were identified. Multiple (2 -7 types) HPV infections were observed in 52.9% of HPV-infected women. The most prevalent HPV types were HPV-52 (14.7%), HPV-35 (9.4%), HPV-58 (9.4%), HPV-51 (8.6%), HPV-16 (7.8%), HPV-31 (7.5%), HPV-53 (6.7%), and HPV-18 (6.4%). Human immunodeficiency virus type 1 (HIV-1) seroprevalence was 36.0%. Human papillomavirus prevalence was significantly higher in HIV-1-infected women (87 vs 54%, prevalence ratio ( Cervical cancer is the most frequent cancer of women in developing countries, particularly in sub-Saharan Africa (Parkin et al, 1999), and it is now well established that genital infection with certain types of human papillomavirus (HPV) causes virtually all cases of cervical intraepithelial neoplasia (CIN) and invasive cervical cancer (ICC) (Walboomers et al, 1999). The HPV types that infect the genital tract have been subdivided into low-risk (LR) types, which are principally found in nonmalignant lesions such as genital warts, and high-risk (HR) types, which are associated with the development of CIN and ICC. Human papillomavirus types 6, 11, 40, 42, 43, 44, 54, 61, 70, 72, 81, and 89 are classified as LR types, whereas types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73, and 82 are classified as HR types. In addition, HPV types 26, 53, and 66 are considered as probably carcinogenic (Muñoz et al, 2003).Human papillomavirus prophylactic vaccines are now being developed and promising results have been obtained with recombinant L1 capsid protein virus-like particles (VLPs). However, the current HPV vaccines target the most prevalent high-risk HPV (HR-HPV) types worldwide, namely HPV-16 and HPV-18 (Koutsky et al, 2002;Ault et al, 2004;Brown et al, 2004;Harper et al, 2004). It has been shown that crossneutralisation induced by L1 VLPs represents less than 1% of the neutralising activity induced by the dominant conformational epitope , indicating that current HPV vaccines would be able to confer only type-specific immunity. Therefore, effectiveness of these vaccines on the prevention of cancer may be lower in populations highly affected by HR-HPV types other than HPV-16 and HPV-18. Thus, it is important to document the distribution of HPV genotypes in HPV-infected women and in women with cervical neoplasia in African countries in order to assess the potential effectiveness of a bivalent HPV-16/18 vaccine.There have been few detailed studies of HPV genotypes and their association with intraepithelial lesions or ICC in sub-Saharan Africa. Available data suggest, however, a higher prevalence and wider spectrum of oncogenic HPV types compared to studies conducted elsewhere (Castellsague et al, 2001;De Vuyst et al, 2003;Mayaud et al, 2003;Clifford et al, 2005;Wall et al, 2005). Furthermore, the high backgr...
Human papillomavirus (HPV) infection and cervical squamous intraepithelial lesions (SILs) were studied in 379 high-risk women. Human papillomavirus DNA was detected in 238 of 360 (66.1%) of the beta-globin-positive cervical samples, and 467 HPV isolates belonging to 35 types were identified. Multiple (2 -7 types) HPV infections were observed in 52.9% of HPV-infected women. The most prevalent HPV types were HPV-52 (14.7%), HPV-35 (9.4%), HPV-58 (9.4%), HPV-51 (8.6%), HPV-16 (7.8%), HPV-31 (7.5%), HPV-53 (6.7%), and HPV-18 (6.4%). Human immunodeficiency virus type 1 (HIV-1) seroprevalence was 36.0%. Human papillomavirus prevalence was significantly higher in HIV-1-infected women (87 vs 54%, prevalence ratio ( Cervical cancer is the most frequent cancer of women in developing countries, particularly in sub-Saharan Africa (Parkin et al, 1999), and it is now well established that genital infection with certain types of human papillomavirus (HPV) causes virtually all cases of cervical intraepithelial neoplasia (CIN) and invasive cervical cancer (ICC) (Walboomers et al, 1999). The HPV types that infect the genital tract have been subdivided into low-risk (LR) types, which are principally found in nonmalignant lesions such as genital warts, and high-risk (HR) types, which are associated with the development of CIN and ICC. Human papillomavirus types 6, 11, 40, 42, 43, 44, 54, 61, 70, 72, 81, and 89 are classified as LR types, whereas types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73, and 82 are classified as HR types. In addition, HPV types 26, 53, and 66 are considered as probably carcinogenic (Muñoz et al, 2003).Human papillomavirus prophylactic vaccines are now being developed and promising results have been obtained with recombinant L1 capsid protein virus-like particles (VLPs). However, the current HPV vaccines target the most prevalent high-risk HPV (HR-HPV) types worldwide, namely HPV-16 and HPV-18 (Koutsky et al, 2002;Ault et al, 2004;Brown et al, 2004;Harper et al, 2004). It has been shown that crossneutralisation induced by L1 VLPs represents less than 1% of the neutralising activity induced by the dominant conformational epitope , indicating that current HPV vaccines would be able to confer only type-specific immunity. Therefore, effectiveness of these vaccines on the prevention of cancer may be lower in populations highly affected by HR-HPV types other than HPV-16 and HPV-18. Thus, it is important to document the distribution of HPV genotypes in HPV-infected women and in women with cervical neoplasia in African countries in order to assess the potential effectiveness of a bivalent HPV-16/18 vaccine.There have been few detailed studies of HPV genotypes and their association with intraepithelial lesions or ICC in sub-Saharan Africa. Available data suggest, however, a higher prevalence and wider spectrum of oncogenic HPV types compared to studies conducted elsewhere (Castellsague et al, 2001;De Vuyst et al, 2003;Mayaud et al, 2003;Clifford et al, 2005;Wall et al, 2005). Furthermore, the high backgr...
Consensus primers targeting human papillomaviruses (HPVs) have biases in sensitivity toward certain HPV types. We applied 3 primer sets (GP51/61, MY09/11, PGMY09/11) in parallel on 120 Chinese cervical cancer specimens. GP51/61 exhibited a poor sensitivity for HPV52, for which the prevalence among squamous cell cervical cancer was underestimated from 14.6% to 0%. The fact that HPV52 should rank second in prevalence among squamous cell cervical carcinoma in Hong Kong could be missed if GP51/61, a worldwide commonly used primer set, was selected for HPV detection. Biases in HPV type-specific sensitivity may result in misprioritization of vaccine candidates. ' 2005 Wiley-Liss, Inc.Key words: human papillomavirus; detection; genotype; vaccine; Chinese; Hong Kong; PCR Cervical cancer is the second most common cancer in women worldwide. Strong and consistent evidence accumulated over the past 2 decades confirms the aetiologic role of human papillomaviruses (HPVs) and provides a strong impetus for developing HPV vaccines to prevent cervical cancer. More than 100 HPV types have been identified, and at least 30 have been found in cervical cancers. 1 Given the diversity of HPV types and the largely typespecific immunity after natural infections, 2-4 it is important to delineate the prevalence of different HPV types found in cervical cancers so as to guide the selection of vaccine candidates. Most studies on HPV have employed consensus primers with an intention to cover a broad spectrum of HPV types. With the more than 10% sequence variation between HPV types, biases in sensitivity of a given primer set toward certain types could happen. In our study, we examined the influence of detection methods on assessing the prevalence of HPVs and thus their priority as cervical cancer vaccine candidates. Material and methodsA total of 120 cervical cancer specimens (105 fresh frozen and 15 paraffin embedded; 89 squamous cell carcinoma, 26 adenocarcinoma, 4 adenosquamous carcinoma and 1 lymphoepitheliod carcinoma) collected from Hong Kong Chinese aged 26-84 years (mean 55 years; SD 13.9) were examined. Total DNA was extracted by the QIAamp DNA mini kit (QIAGEN, Hilden, Germany) and with the quality of extracted preparations confirmed by beta-globin PCR. 5 The clinical materials were collected with a written informed consent. Our study was approved by the local institutional ethics committee, and the human experimentation guidelines of the local institute were followed in the conduct of our study.HPV detection and typing was accomplished by 3 different methods in parallel. In the first method, HPV DNA was amplified by the GP51/61 primers that target an approx. 150 bp fragment of the L1 region. 5,6 The HPV type was identified by direct sequencing of PCR amplicons. In the second method, the MY09/ 11 primers that target an approx. 450 bp fragment of the L1 region was used for PCR. 7,8 HPV type was identified by restriction fragment length polymorphisms (RFLPs) using endonucleases RsaI and DdeI as previously described. 8 Ambiguous RFLPs w...
Data on the prevalence of human papillomavirus (HPV) types in cervical carcinoma in women with HIV are scarce but are essential to elucidate the influence of immunity on the carcinogenicity of different HPV types, and the potential impact of prophylactic HPV vaccines in populations with high HIV prevalence. We conducted a multicentre case-case study in Kenya and South Africa. During 2007-2009, frozen tissue biopsies from women with cervical carcinoma were tested for HPV DNA using GP51/61-PCR assay. One hundred and six HIV-positive (mean age 40.8 years) and 129 HIV-negative women (mean age 45.7) with squamous cell carcinoma were included. Among HIV-positive women, the mean CD4 count was 334 cells/lL and 48.1% were on combined antiretroviral therapy. HIV-positive women had many more multiple HPV infections (21.6% of HPV-positive carcinomas) compared with HIV-negative women (3.3%) (p < 0.001) and the proportion of multiple infections was inversely related to CD4 level. An excess of HPV18 of borderline statistical significance was found in HIV-positive compared with HIVnegative cases (Prevalence ratio (PR) 5 1.9, 95% confidence interval (CI): 1.0-3.7, adjusted for study centre, age and multiplicity of infection). HPV16 and/or 18 prevalence combined, however, was similar in HIV-positive (66.7%) and HIVnegative cases (69.1%) (PR 5 1.0, 95% CI: 0.9-1.2). No significant difference was found for other HPV types. Our data suggest that current prophylactic HPV vaccines against HPV16 and 18 may prevent similar proportions of cervical SCC in HIVpositive as in HIV-negative women provided that vaccine-related protection is sustained after HIV infection. Infection with high-risk (HR) human papillomavirus (HPV)is a necessary cause for invasive cervical carcinoma. Worldwide HPV16 and 18 are found in 57% and 16% of cervical carcinomas, respectively, according to the findings of a recent meta-analysis 1 and are targeted by the current prophylactic HPV vaccines for cervical carcinoma prevention. HIV-positive women are at increased risk for HPV infection and progression to cervical intraepithelial neoplasia grade 3 (CIN3). 2Linkage studies between HIV/AIDS and cancer registries have shown a 2-to 22-fold increased invasive cervical carcinoma incidence in HIV-positive women compared with the general female population from the same area, depending upon the life expectancy of HIV-positive women and the coverage and quality of cervical cancer screening in different countries. 3,4 HPV16 infection and HPV16-associated precancerous lesions were reported to be less dependent on a woman's immune status compared with other HR HPV types.5 Indeed, a meta-analysis of HPV prevalence in HIV-positive women worldwide showed a relative underrepresentation of HPV16 and overrepresentation of the other HR HPV types in HIVpositive compared with HIV-negative women with or without cervical abnormalities. 6 The lower prevalence of HPV16 in CIN2/3 (the endpoint lesions used in the evaluation of HPV vaccine efficacy) raised the fear that vaccination may preven...
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