| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1 State Key Laboratory of Biocontrol, Key Laboratory of Genetic Engineering of MOE, Department of Biochemistry, School of Life Sciences, Sun Yat-Sen (Zhongshan) University, Guangzhou 510275, People's Republic of China
2 Department of Oncology, Maternal and Child Health Hospital of Jiangxi Province, Nanchang, People's Republic of China
3 Department of Gynecology, People Hospital of Zhuhai, Guangdong Province, People's Republic of China
Correspondence
Yuping Wu
exwyp{at}163.com
 |
ABSTRACT |
|---|
 TOP ABSTRACT INTRODUCTIONMETHODSRESULTSDISCUSSIONREFERENCES |
|---|
|
INTRODUCTION |
|---|
|
TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONREFERENCES |
|---|
). It has been coevolving with its natural hosts for several million years (Ho et al., 1991). This DNA virus acts by the expression of two viral oncoproteins, E6 and E7. However, not all cervical infections with oncogenic HPV types will progress to cervical cancer. Factors that are described to be important in the risk of progression to cancer are of both host and viral origin. One viral factor is the type/subtype of the papillomavirus involved. Almost 30 distinct types of HPV, both oncogenic and non-oncogenic, have been described to infect the genital tract. Our previous study showed, by using hybrid capture 2, that high-risk HPV prevalence was 89·9 % (427/475) in invasive cervical cancer (ICC) (Wu et al., 2006a). The most common HPV DNA type found in cervical cancers among Chinese women was HPV16 (79·6 %), followed by HPV58 (5·92 %) and HPV33 (3·29 %) (Wu et al., 2006a). Other research reports that HPV16 is the most common, being associated with >50 % of cervical cancers (Muñoz, 2000). HPV16 variants are described in phylogenetic branches, the distribution of which varies geographically. The prototype described by Seedorf et al. (1985) is a German isolate and a member of the European (E) branch. The other branches of variants that have been described are: Asian (As), mainly in South-East Asia; Asian–American (AA), mainly in Central and South America; the African-1 (Af1) and African-2 (Af2) variants, which are mainly found in Africa; the North American variant (NA1) in America (Ho et al., 1991); and a recently discovered Javanese variant (Java) in Indonesia (de Boer et al., 2004). The European variants are found in all other regions except for Africa. The E and the As branches are closely related, such that the As variant appears to be a subclass of the E lineage (Yamada et al., 1997). Naturally occurring HPV16 variants differ in certain biological and biochemical properties that might result in differences in pathogenicity. However, epidemiological studies on the oncogenic risk of HPV16 variants have produced different conclusions, and the risk association seems to vary with the population studied (Bontkes et al., 1998; Zehbe et al., 1998; Nindl et al., 1999).
Persistent infection with HPV may depend on certain characteristics, such as HPV types and variants, high viral load and the host cellular immune response to HPV infection (Wu et al., 2006a, b). Xi et al. (1995) reported that 10–20 % of specimens showed evidence of infection by multiple variants, of which one major variant seemed to predominate over time, whereas minor variants appeared more transient. These results suggest that HPV16 establishes a persistent infection in which a single variant predominates; coinfection with additional HPV16 variants results in a minor population of HPV16 genomes (Xi et al., 1995). Preliminary studies (Song et al., 1997; Nindl et al., 1999) have suggested that variants of HPV16 may show varying degrees of association with cervical neoplasia. This may partially explain why some HPV16 infections progress to high-grade intraepithelial lesions or cancer, whereas others do not. If causal, these associations may be explained by differences in the transcriptional regulation of the virus by different variants, in the biological activities of the proteins encoded by HPV16 variants (e.g. enhanced transforming abilities of E6/E7) or in the ability of the host to respond immunologically to specific viral epitopes encoded by variants. This latter effect is likely to be mediated in part through human leukocyte antigen (HLA) presentation of viral antigens (Ellis et al., 1995; Hildesheim, 1997; Zehbe et al., 2001, 2003). It is not known to what extent these variant HLA genes may influence host immune response and recognition.
China has one of the highest incidence rates of cervical cancer (over 27 cases per 100 000 women) and approximately 132 300 new cases are reported every year (Parkin et al., 1999). The prevalence of HPV16, the most common type found in cervical cancers, was 79·6 % in Jiangxi, central China (Wu et al., 2006a), 60·2 % in Hunan and Guangzhou, southern China (Liu et al., 2004), and 57·7 % in Australia (Liu et al., 2004). Cervical cancer rates are still higher in China, despite equivalent HPV16 prevalence, and thus could be attributed to differential variant frequency, with certain variants conferring greater oncogenicity. Although certain parts of China have the highest incidence of cervical cancer in the world (Zhang, 1986), there are few data on the epidemiology of HPV variants among cervical cancers of Chinese women. This study examined the sequence variation of E6 and E7 oncogenes and partial L1 sequences of HPV16 and evaluated their oncogenic implications among cervical cancers in China.
|
METHODS |
|---|
|
TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONREFERENCES |
|---|
). Women in the control group were similar to cervical cancer patients with respect to ethnicity, marital status and smoking habits. Cervical-cell samples were obtained for cytological screening and detection of HPV DNA. Women with abnormal cytology were referred for expert colposcopy and histological verification. Cervical samples were collected at the date of diagnosis, before therapy and follow-up were initiated. A cervical specimen was obtained for cytology before the specimen for HPV DNA testing was taken. Written informed consent was obtained from all patients and controls, as per the guidelines of the institutional review board. The study protocol was reviewed and approved by the institutional review committees.
|
.
HPV typing confirmed by sequencing.
HPV detection and typing were confirmed by the general primer PCR and sequence-based typing (PCR-SBT) method (Gravitt et al., 2003). The nested PCR was performed by using MY09/MY11 and GP5+/GP6+ primers. Amplification of a 268 bp fragment of the 
-globin gene was used to assess human DNA quality (Lefevre et al., 2003). The PCR products were separated by electrophoresis on 2 % agarose and the HPV amplification products were purified by PCR purification (Qiagen) and sequenced directly by using an ABI Prism BigDye Terminator cycle sequencing ready reaction kit (PE Biosystems) on an ABI 310 DNA analyser. Nucleotide sequences were aligned and compared with those of known HPV types available through GenBank by using the BLAST 2.0 software server (http://www.ncbi.nih.gov/blast). In accordance with established guidelines, a nucleotide sequence was assigned to an HPV type if it corresponded with a known HPV genotype by >95 % (Gravitt et al., 2003).
Variant identification.
HPV16 E6- and E7-specific PCR was performed with primers flanking the coding region of HPV16 E6 (nt 52–575) (Zehbe et al., 2001): 5'-CGAAACCGGTTAGTATAA-3' and 5'-GTATCTCCATGCATGATT-3'; and E7 (nt 480–985): 5'-ATAATATAAGGGGTCGGTGG-3' and 5'-CATTTTCGTTCTCGTCATCTG-3'. For HPV16 E6/E7, PCR was performed in a 50 µl volume containing 1x PCR buffer, 2·5 mM MgCl2, 200 µM each dNTP, 0·5 µM sense and antisense primers, 20 ng genomic DNA and 0·5 U Taq DNA polymerase (Perkin Elmer) with a 35-cycle protocol: 1 min denaturation at 94 °C, 1 min annealing at 55 °C and 1 min extension at 72 °C, with 5 min initial denaturation at 94 °C and 7 min final elongation at 72 °C. PCR products were tested on an ethidium bromide-stained 2 % agarose gel. For positive products, a sequencing reaction was performed according to the manufacturer's protocol (BigDye Terminator cycle sequencing kit; PE Biosystems). Sequencing was performed separately with both forward and reverse primers and repeated three times. Only data with no discrepancies were used for analysis. Samples were classified into phylogenetic branches from variation in the E6 region and the MY09/11 region of the L1 region, as described by Yamada et al. (1997). The prototype type sequence (HPV16R), which belongs to the European lineage, was used for comparison and nucleotide-position numbering (Seedorf et al., 1985). HPV16 sequences and base positions were numbered according to the 1997 sequence database (Los Alamos National Laboratory, Los Alamos, NM, USA) and variant designation was done according to Yamada et al. (1997).
Data analysis.
Statistical analysis was performed with SPSS 10.0 software. The questionnaire data and HPV results were entered into a computerized database. Differences in mean ages were analysed by Student's t-test. Chi-squared (
2) tests were used on appropriate data to identify any differences in demographical and risk factors between cervical cancer patients and controls. P values (two-tailed) of <0·05 were considered statistically significant.
|
RESULTS |
|---|
|
TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONREFERENCES |
|---|
), As, E, AA, Af1 and Af2 variants.
HPV16 E6 variants have extensive nucleotide changes
Nucleotide sequences of the full open reading frame of HPV16 E6 from 55 cases of HPV16-positive cervical cancers were determined and compared with the HPV16 reference DNA sequence (Seedorf et al., 1985). As shown in Table 2, there was no evidence of premature stop codons or deletions. By comparison with the prototype sequence of HPV16 E6, 10 variations (eight mis-sense and two silent) were found. As indicated in Table 2, the nucleotide variations were not distributed randomly. There were two common variation sites: nt 178 (18 out of 55 cases had the prototype nucleotide T, 36 out of 55 cases had G, one out of 55 cases had A) and nt 442 (eight out of 55 cases had C, 47 out of 55 cases had the prototype nucleotide A). Both of the nucleotide variations caused amino acid variations and hence were termed mis-sense variations. The variation at nt 178 will result in either an aspartic acid or a glutamic acid at aa 25 of the E6 protein, i.e. D25E, whilst variation 442 encodes either glutamic acid or aspartic acid at aa 113 (E113D).
|
). It was found that the nucleotide variation rate in the HPV16 E6 region was 90·9 % (50 out of 55) for cervical cancer in this study. The mean age of Chinese cervical cancer patients carrying the prototype was 50·54±10·91 years, and that of carriers of the As variant was 42·98±10·43 years. It was also found that As-positive cervical cancer patients were 7·56 years younger than prototype-positive ones.
Sequence variations of HPV16 oncogene E7
Our results showed that nucleotide sequences of the full open reading frame of HPV16 E7 from 47 cervical cancers with HPV16 infection were determined and compared with the HPV16 reference DNA sequence (Seedorf et al., 1985). As shown in Table 3, variations covered nearly the whole length of the open reading frame of the gene: E7 had 10 variations, with seven mis-sense and three silent. The nucleotide variations were not distributed randomly. There were three common variation sites: nt 647 (33 out of 47 were G, 14 out of 47 were A), nt 749 (24 out of 47 were T, 23 out of 47 were C) and nt 846 (18 out of 47 were T, 29 out of 47 were C). Nucleotide variations at nt 647 and 749 caused amino acid variations, resulting in N29S and S63F, whereas that at nt 846 was a silent variation. In addition to N29S and S63F, the following E7 variations were found in this study: N29H, F57L, V55I, R77C and L15F (Table 3). It was found that the nucleotide variation rate in the HPV6 E7 region was 100 % (47 out of 47) for cervical cancer.
|
). HPV16 DNA of healthy-control subjects was also examined. It was shown that there was a nucleotide variation at position T6699C of HPV16 L1, resulting in amino acid substitution Y381H (8·3 %, one out of 12) in healthy-control subjects. As shown in Table 4, HPV16 partial L1 sequences of cervical cancers had 10 variations, with six mis-sense and four silent. The following L1 variations were found in cervical cancers in this study: S377A, K387E, E378D, K382E and T379P. It was also found that the nucleotide variation rate in the HPV16 partial L1 region was 6·87 % (nine of 131) for cervical cancer and 8·3 % (one of 12) for control subjects with HPV16 infection. A majority of the isolates belonged to the As or prototype (98·5 %, 129/131) lineages. Only one isolate belonged to Af1 and another isolate belonged to AA/Af2 lineages (Table 4).
|
|
DISCUSSION |
|---|
|
TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONREFERENCES |
|---|
); some of these are associated with amino acid changes in functional and/or antigenic domains and are liable to introduce unique biological and immunogenic properties, conferring differences in behaviour from each other and from the prototype. The E6 gene of HPV16 has frequent sequence variations. Some variants have been associated with a higher risk of ICC than others (Yamada et al., 1995; Zehbe et al., 1998). Zehbe et al. (1998) suggested that the intratypic sequence variation in E6 could predict risk of progression from cervical intraepithelial neoplasia (CIN) 3 to ICC. The conclusion was that CIN 3 caused by variant HPV16 would be much more likely to progress to invasion than that harbouring the prototype strain (Zehbe et al., 1998).
Previous studies by Yamada et al. (1997) reported that the prevalence of the prototype E6 gene, first isolated from a German patient with ICC, was 34 % in European populations. Subsequently, Zehbe et al. (1998) showed that the prototype E6 gene was found in only 6 % of ICCs in Swedish populations, close to what Radhakrishna Pillai et al. (2002) found in Indian populations (9·1 %). Similar results were reported from Sweden (Andersson et al., 2000), where predominance of the L83V mutation appeared to result in increased transforming potential of HPV16 in both squamous and glandular cervical lesions. However, other reports from Germany and Russia did not support a role for the L83V mutation in increasing the risk of ICC (Nindl et al., 1999; Hu et al., 2001). In a study on Mexican patients (Berumen et al., 2001), 3·3 % of the population had the prototype E6, whilst the L83V variant was seen in 23·8 % of patients. The characteristic mutations associated with the AA HPV16 variant were seen in 23·2 % of cancer patients in this population. Our results demonstrated that only 3·6 % of cervical cancers with the characteristic E variants had the L83V mutation, 65·5 % had the D25E mutation, 14·5 % had the E113D mutation, 7·3 % had the R129K mutation and 5·5 % had the H78Y mutation; other mutations in the E6 gene included F69L, E89Q and S138C. We found that the D25E variant was the most prevalent variant in ICC in the Chinese population. This finding is compatible with a report that the D25E variant is the most prevalent in ICC (85·2 %) in Korean women (Kang et al., 2005). A previous report showed that other variations in E6 (E/G131T) result in amino acid changes in potential T-cell receptor- or HLA-binding regions (Ellis et al., 1995). Data correlating viral persistence and cervical disease progression with different variants are, however, inconclusive (Ellis et al., 1995; Bontkes et al., 1998). Some data suggest that women infected with certain variants have a significantly greater chance of developing a high-grade lesion (Villa et al., 2000). In some studies, the variant with the T350G change in E6 (L83V) was associated with an increased risk of cervical disease progression compared with the prototype strain (Zehbe et al., 1998; Kämmer et al., 2002).
Our results found that the prevalences of three hot spots of E7 nucleotide variation (nt 647 A
G, resulting in N29S, nt 749 CT, resulting in S63F, and nt 846 TC, a silent variation) were 70·2 % (33/47), 51·1 % (24/47) and 61·7 % (29/47) in Chinese cervical cancers, respectively. A previous study from Japan found two hot spots of E7 nucleotide variation, nt 647 AG and nt 846 TC, that were detected in nine of 15 and seven of 15 cases, respectively (Fujinaga et al., 1994). Chan et al. (2002) also observed a high frequency of these substitutions (58·0 % for nt 647 AG and 52·9 % for nt 846 TC). The reported prevalence of the nt 647 AG mutation varies: 14·3 % for Sichuan in central China (Stephen et al., 2000), 59·5 % for Korea (Song et al., 1997), 0·9 % for Germany (Nindl et al., 1999) and 36·4 % for Tanzania (Eschle et al., 1992). This may reflect the high prevalence of Asian isolates among these populations. In contrast, they are uncommon among European isolates and occurred individually. These findings suggest that sequence variations at E7 also display geographical dependence. The most reported amino acid change in the HPV16 E7 open reading frame, the asparagine to serine mutation at position 29 (N29S), is likely to be significant because of its location in an immunoreactive region (Zehbe et al., 1998). Our results showed that amino acid change N29S was more frequent in Chinese cervical cancers. One survey among Korean women reports that this mutation was significantly more frequent in carcinomas (70 %) than in the control group (33 %) or the CIN 3 group (50 %) (Song et al., 1997). However, in southern China and Japan, this variant was distributed equally among subjects (Fujinaga et al., 1994; Chan et al., 2002). In an Indian population, no associations were found between the E7 variant and tumour stage or age (Radhakrishna Pillai et al., 2002). Altogether, data about the oncogenicity of the variant are contradictory. However, the mutation N29S was found to be significantly more prevalent, 70 % (33/47), in Chinese cervical cancers in our study.
Some HPV variants may evade the natural immune response (Etherington et al., 1999; Hildesheim & Wang, 2002). As we reported previously (Wu et al., 2006a), the oncogenicity of some variants seems to vary geographically and with the ethnicity of the studied population. This difference may be explained by the distribution of the highly polymorphic HLA type, because some HLA alleles might present specific epitopes from variants more efficiently. Some studies have tried to identify whether specific variants are associated with different HLA alleles (Ellis et al., 1995; Terry et al., 1997; Bontkes et al., 1998; Zehbe et al., 2001; Matsumoto et al., 2003), but the conclusions were limited because the ethnic population or sample size was too small to provide conclusive results (Hildesheim & Wang, 2002).
Our results show that the epidemiology and risk implications of HPV16 intratypic variants in China are markedly different from elsewhere in the world. HPV16 As variants may be linked to a high incidence of cervical cancer in China, with some evidence suggesting that they may be more oncogenic than the prototype, including their association with younger women. This complex relationship between viral and host risk markers can be analysed by direct nucleotide sequencing, and such an approach has a good potential to define more precisely the risk factors that may predispose individuals to oncogenic HPV infection, even developing into cervical cancer. If amino acid changes in the E6 protein are located in regions critical for immune recognition, vaccines developed for a particular variant virus type may have a reduced efficiency against other variants. Vaccines against HPV are under development. It is not clear to what extent cross-reactivity in immune response exists between HPV16 intratypic variants, but knowledge about HPV variants may be important for vaccine development and relevant research is needed urgently.
Although this study represents the large dataset of HPV16 variation reported to date in China, our investigation was still limited by sample size. Greater numbers of specimens must be analysed to provide further regional prevalence and country-specific data. Future case–control and longitudinal studies will be necessary to estimate the individual disease risk of each variant and to establish the prevalence of HPV variants in specific populations. This study may form a basis for those further investigations. The simplified detection of HPV16 variants will also facilitate the distinction of recurrent and new infections more reliably in epidemiological studies of infection and persistence. Diverse and comprehensive research efforts are required to elucidate a biological understanding of HPV intratypic variation. We do not yet understand whether amino acid variation in HPV antigens influences host immune response and recognition. Even more complex is the question of whether specific virus variants pose distinct challenges in specific host immunogenetic backgrounds (e.g. HLA haplotypes).
In summary, this study provides a report on HPV16 E6, E7 and partial L1 gene variations from China and provides evidence for the association of specific E6 gene variants with the risk of cervical cancer.
|
ACKNOWLEDGEMENTS |
|---|
|
REFERENCES |
|---|
|
TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONREFERENCES |
|---|
Baay, M. F. D., Quint, W. G. V., Koudstaal, J., Hollema, H., Duk, J. M., Burger, M. P. M., Stolz, E. & Herbrink, P. (1996). Comprehensive study of several general and type-specific primer pairs for detection of human papillomavirus DNA by PCR in paraffin-embedded cervical carcinomas. J Clin Microbiol 34, 745–747.[Abstract]
Berumen, J., Ordoñez, R. M., Lazcano, E. & 7 other authors (2001). Asian-American variants of human papillomavirus 16 and risk for cervical cancer: a case–control study. J Natl Cancer Inst 93, 1325–1330.
Bontkes, H. J., van Duin, M., de Gruijl, T. D. & 11 other authors (1998). HPV 16 infection and progression of cervical intra-epithelial neoplasia: analysis of HLA polymorphism and HPV 16 E6 sequence variants. Int J Cancer 78, 166–171.[CrossRef][Medline]
Chan, P. K. S., Lam, C. W., Cheung, T. H., Li, W. W. H., Lo, K. W. K., Chan, M. Y. M., Cheung, J. L. K., Xu, L. Y. & Cheng, A. F. (2002). Human papillomavirus type 16 intratypic variant infection and risk for cervical neoplasia in southern China. J Infect Dis 186, 696–700.[CrossRef][Medline]
de Boer, M. A., Peters, L. A. W., Aziz, M. F., Siregar, B., Cornain, S., Vrede, M. A., Jordanova, E. S., Kolkman-Uljee, S. & Fleuren, G. J. (2004). Human papillomavirus type 16 E6, E7, and L1 variants in cervical cancer in Indonesia, Suriname, and The Netherlands. Gynecol Oncol 94, 488–494.[Medline]
Ellis, J. R. M., Keating, P. J., Baird, J. & 8 other authors (1995). The association of an HPV16 oncogene variant with HLA-B7 has implications for vaccine design in cervical cancer. Nat Med 1, 464–470.[CrossRef][Medline]
Eschle, D., Dürst, M., ter Meulen, J., Luande, J., Eberhardt, H. C., Pawlita, M. & Gissmann, L. (1992). Geographical dependence of sequence variation in the E7 gene of human papillomavirus type 16. J Gen Virol 73, 1829–1832.
Etherington, I. J., Ellis, J. R., Luesley, D. M., Moffitt, D. D. & Young, L. S. (1999). Histologic and immunologic associations of an HPV16 variant in LoSIL smears. Gynecol Oncol 72, 56–59.[CrossRef][Medline]
Fujinaga, Y., Okazawa, K., Nishikawa, A., Yamakawa, Y., Fukushima, M., Kato, I. & Fujinaga, K. (1994). Sequence variation of human papillomavirus type 16 E7 in preinvasive and invasive cervical neoplasias. Virus Genes 9, 85–92.[CrossRef][Medline]
Gravitt, P. E., Burk, R. D., Lorincz, A. & 7 other authors (2003). A comparison between real-time polymerase chain reaction and hybrid capture 2 for human papillomavirus DNA quantitation. Cancer Epidemiol Biomarkers Prev 12, 477–484.
Hildesheim, A. (1997). Human papillomavirus variants: implications for natural history studies and vaccine development efforts. J Natl Cancer Inst 89, 752–753.
Hildesheim, A. & Wang, S. S. (2002). Host and viral genetics and risk of cervical cancer: a review. Virus Res 89, 229–240.[CrossRef][Medline]
Ho, L., Chan, S.-Y., Chow, V., Chong, T., Tay, S.-K., Villa, L. L. & Bernard, H.-U. (1991). Sequence variants of human papillomavirus type 16 in clinical samples permit verification and extension of epidemiological studies and construction of a phylogenetic tree. J Clin Microbiol 29, 1765–1772.
Hu, X., Pang, T., Guo, Z., Mazurenko, N., Kisseljov, F., Pontén, J. & Nistér, M. (2001). HPV16 E6 gene variations in invasive cervical squamous cell carcinoma and cancer in situ from Russian patients. Br J Cancer 84, 791–795.[Medline]
Kämmer, C., Tommasino, M., Syrjänen, S., Delius, H., Hebling, U., Warthorst, U., Pfister, H. & Zehbe, I. (2002). Variants of the long control region and the E6 oncogene in European human papillomavirus type 16 isolates: implications for cervical disease. Br J Cancer 86, 269–273.[CrossRef][Medline]
Kang, S., Jeon, Y. T., Kim, J. W., Park, N. H., Song, Y. S., Kang, S. B. & Lee, H. P. (2005). Polymorphism in the E6 gene of human papillomavirus type 16 in the cervical tissues of Korean women. Int J Gynecol Cancer 15, 107–112.[Medline]
Lefevre, J., Hankins, C., Pourreaux, K., Voyer, H. & Coutlée, F. (2003). Real-time PCR assays using internal controls for quantitation of HPV-16 and -globin DNA in cervicovaginal lavages. Canadian Women's HIV Study Group. J Virol Methods 114, 135–144.[CrossRef][Medline]
Liu, J., Rose, B., Huang, X., Liao, G., Carter, J., Wu, X. & Thompson, C. (2004). Comparative analysis of characteristics of women with cervical cancer in high- versus low-incidence regions. Gynecol Oncol 94, 803–810.[Medline]
Matsumoto, K., Yasugi, T., Nakagawa, S., Okubo, M., Hirata, R., Maeda, H., Yoshikawa, H. & Taketani, Y. (2003). Human papillomavirus type 16 E6 variants and HLA class II alleles among Japanese women with cervical cancer. Int J Cancer 106, 919–922.[Medline]
Muñoz, N. (2000). Human papillomavirus and cancer: the epidemiological evidence. J Clin Virol 19, 1–5.[CrossRef][Medline]
Nindl, I., Rindfleisch, K., Lotz, B., Schneider, A. & Dürst, M. (1999). Uniform distribution of HPV 16 E6 and E7 variants in patients with normal histology, cervical intra-epithelial neoplasia and cervical cancer. Int J Cancer 82, 203–207.[CrossRef][Medline]
Parkin, D. M., Pisani, P. & Ferlay, J. (1999). Estimates of the worldwide incidence of 25 major cancers in 1990. Int J Cancer 80, 827–841.[CrossRef][Medline]
Radhakrishna Pillai, M., Sreevidya, S., Pollock, B. H., Jayaprakash, P. G. & Herman, B. (2002). Human papillomavirus type 16 E6 and E7 gene variations in Indian cervical cancer. Gynecol Oncol 87, 268–273.[CrossRef][Medline]
Seedorf, K., Krämmer, G., Dürst, M., Suhai, S. & Röwekamp, W. G. (1985). Human papillomavirus type 16 DNA sequence. Virology 145, 181–185.[CrossRef][Medline]
Song, Y. S., Kee, S. H., Kim, J. W., Park, N. H., Kang, S. B., Chang, W. H. & Lee, H. P. (1997). Major sequence variants in E7 gene of human papillomavirus type 16 from cervical cancerous and noncancerous lesions of Korean women. Gynecol Oncol 66, 275–281.[CrossRef][Medline]
Stephen, A. L., Thompson, C. H., Tattersall, M. H., Cossart, Y. E. & Rose, B. R. (2000). Analysis of mutations in the URR and E6/E7 oncogenes of HPV 16 cervical cancer isolates from central China. Int J Cancer 86, 695–701.[CrossRef][Medline]
Terry, G., Ho, L. & Cuzick, J. (1997). Analysis of E2 amino acid variants of human papillomavirus types 16 and 18 and their associations with lesion grade and HLA DR/DQ type. Int J Cancer 73, 651–655.[CrossRef][Medline]
Villa, L. L., Sichero, L., Rahal, P., Caballero, O., Ferenczy, A., Rohan, T. & Franco, E. L. (2000). Molecular variants of human papillomavirus types 16 and 18 preferentially associated with cervical neoplasia. J Gen Virol 81, 2959–2968.
Wu, Y., Chen, Y., Li, Y., Yu, G., Zhang, Y. & He, Y. (2006a). Associations of high-risk HPV types and viral load with cervical cancer in China. J Clin Virol 35, 264–269.[Medline]
Wu, Y., Chen, Y., Li, Y. & 8 other authors (2006b). Polymorphic amino acids at codons 9 and 37 of HLA-DQB1 alleles may confer susceptibility to cervical cancer among Chinese women. Int J Cancer (in press). doi:10.1002/ijc.21746
Xi, L. F., Demers, G. W., Koutsky, L. A., Kiviat, N. B., Kuypers, J., Watts, D. H., Holmes, K. K. & Galloway, D. A. (1995). Analysis of human papillomavirus type 16 variants indicates establishment of persistent infection. J Infect Dis 172, 747–755.[Medline]
Yamada, T., Wheeler, C. M., Halpern, A. L., Stewart, A.-C. M., Hildesheim, A. & Jenison, S. A. (1995). Human papillomavirus type 16 variant lineages in United States populations characterized by nucleotide sequence analysis of the E6, L2, and L1 coding segments. J Virol 69, 7743–7753.[Abstract]
Yamada, T., Manos, M. M., Peto, J., Greer, C. E., Muñoz, N., Bosch, F. X. & Wheeler, C. M. (1997). Human papillomavirus type 16 sequence variation in cervical cancers: a worldwide perspective. J Virol 71, 2463–2472.[Abstract]
Zehbe, I., Wilander, E., Delius, H. & Tommasino, M. (1998). Human papillomavirus 16 E6 variants are more prevalent in invasive cervical carcinoma than the prototype. Cancer Res 58, 829–833.
Zehbe, I., Tachezy, R., Mytilineos, J. & 7 other authors (2001). Human papillomavirus 16 E6 polymorphisms in cervical lesions from different European populations and their correlation with human leukocyte antigen class II haplotypes. Int J Cancer 94, 711–716.[CrossRef][Medline]
Zehbe, I., Mytilineos, J., Wikström, I., Henriksen, R., Edler, L. & Tommasino, M. (2003). Association between human papillomavirus 16 E6 variants and human leukocyte antigen class I polymorphism in cervical cancer of Swedish women. Hum Immunol 64, 538–542.[CrossRef][Medline]
Zhang, J. M. (1986). The distribution and characteristics of carcinoma of the cervix uteri in Lue Yang county. Zhonghua Liu Xing Bing Xue Za Zhi 7, 343–345 (in Chinese).[Medline]
Received 30 October 2005;
accepted 25 January 2006.
This article has been cited by other articles:
|
|
 |
|
  S. Pande, N. Jain, B. K. Prusty, S. Bhambhani, S. Gupta, R. Sharma, S. Batra, and B. C. Das Human Papillomavirus Type 16 Variant Analysis of E6, E7, and L1 Genes and Long Control Region in Biopsy Samples from Cervical Cancer Patients in North India J. Clin. Microbiol., March 1, 2008; 46(3): 1060 - 1066. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| INT J SYST EVOL MICROBIOL | MICROBIOLOGY | J GEN VIROL |
| J MED MICROBIOL | ALL SGM JOURNALS | |
