BMC Infectious Diseases | |
Analysis of mutations in the E6 oncogene of human papillomavirus 16 in cervical cancer isolates from Moroccan women | |
Mohammed El Mzibri3  Mohammed Attaleb3  Abdellatif Benider2  Noureddine Benjaafar1  Chakib Nejjari5  Laila Benbacer3  My Mustapha Ennaji6  Mohamed Berraho5  Meriem Khyatti4  Zineb Qmichou6  | |
[1] Service de radiothérapie, Institut National d'Oncologie de Rabat, Rabat, Morocco;Centre Mohammed VI pour le Traitement des Cancers, Casablanca, Morocco;Unité de Biologie et Recherche Médicale, Centre National de l'Energie, des Sciences et des Techniques Nucléaires, (CNESTEN), BP 1382 RP, 10001 Rabat, Morocco;Laboratoire d’Oncovirologie. Institut Pasteur du Maroc, Casablanca, Morocco;Laboratoire d'Epidémiologie, Recherche clinique et Santé Communautaire, Faculté de Médecine et de Pharmacie, Fès, Morocco;Laboratoiore de Microbiologie, Hygiène et Virologie, FST Mohammedia, Mohammedia, Morocco | |
关键词: Morocco; E6; Variants; Human papillomavirus 16; Cervical cancer; | |
Others : 1146098 DOI : 10.1186/1471-2334-13-378 |
|
received in 2013-05-03, accepted in 2013-08-15, 发布年份 2013 | |
【 摘 要 】
Background
Worldwide, cervical cancer is the second most common cancer in women. High-risk human papillomavirus (HPV) play a crucial role in the etiology of cervical cancer and the most prevalent genotype is HPV16. HPV 16 intratypic variants have been reported to differ in their prevalence, biological and biochemical properties. The present study was designed to analyze and identify HPV type 16 E6 variants among patients with cervical cancer in Morocco.
Methods
A total of 103 HPV16 positive samples were isolated from 129 cervical cancer cases, and variant status was subsequently determined by DNA sequencing of the E6 gene.
Results
Isolates from patients were grouped into the European (E), African (Af) and North-American (NA1) phylogenetic clusters with a high prevalence of E lineage (58.3%). The Af and NA1 variants were detected in 31.1% and 11.6% of the HPV16 positive specimens, respectively, whereas, only 3% of cases were prototype E350T. No European-Asian (EA), Asian (As) or Asian-American (AA) variants were observed in our HPV16-positive specimens. At the amino acid level, the most prevalent non-synonymous variants were L83V (T350G), H78Y (C335T), E113D (A442C), Q14D (C143G/G145T) and R10I (G132T), and were observed respectively in 65%, 41.8%, 38.8%, 30.1% and 23.3% of total samples.
Moreover, HPV16 European variants were mostly identified in younger women at early clinical diagnosis stages. Whereas, HPV16 Af variants were most likely associated with cervical cancer development in older women with pronounced aggressiveness.
Conclusion
This study suggests a predominance of E lineage strains among Moroccan HPV 16 isolates and raises the possibility that HPV16 variants have a preferential role in progression to malignancy and could be associated with the more aggressive nature of cervical cancer.
【 授权许可】
2013 Qmichou et al.; licensee BioMed Central Ltd.
【 预 览 】
Files | Size | Format | View |
---|---|---|---|
20150403091129424.pdf | 231KB | download |
【 参考文献 】
- [1]Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM: Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 2010, 127:2893-2917.
- [2]Benider A, Bennani Othmani M, Harif M, Karkouri M, Quessar A, Sahraoui S, Sqali S: Registre des cancers de la région du grand Casablanca, année 2004. Edition. 2007, 73.
- [3]Smith JS, Lindsay L, Hoots B, Keys J, Franceschi S, Winer R, Clifford GM: Human papillomavirus type distribution in invasive cervical cancer and high-grade cervical lesions: a meta-analysis update. Int J Cancer 2007, 121:621-632.
- [4]Lalaoui K, El Mzibri M, Amrani M, Belabbas MA, Lazo PA: Human papillomavirus DNA in cervical lesions from Morocco and its implications for cancer control. Clin Microbiol Infect 2003, 9:144-148.
- [5]El Mzibri M, Amrani M, Khair MM, Attaleb M, Jaddi H, Ennaji MM, Khan B, Belabbas MA: Prevalence of human papilloma virus infection in malignant lesions of the uterine cervix in Morocco. World J Nucl Med 2009, 8:192-196.
- [6]Meftah El khair M, Ennaji MM, El kebbaj R, Ait Mhand R, Attaleb M, El Mzibri M: p53 Codon 72 polymorphism and risk of cervical carcinoma in Moroccan women. Med Oncol 2010, 27:861-866.
- [7]de Villiers E, Fauquet C, Broker TR, Bernard HU, zur Hausen H: Classification of papillomaviruses. Virology 2004, 324:17-27.
- [8]Yamada T, Wheeler CM, Halpern AL, Stewart AC, Hildesheim A, Jenison SA: 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 1995, 69:7743-7753.
- [9]Zur Hausen H: Papillomaviruses and cancer: from basic studies to clinical application. Nat Rev Cancer 2002, 2:342-350.
- [10]Lizano M, Berumen J, Garcia-Carranca A: HPV-related carcinogenesis: basic concepts, viral types and variants. Arch Med Res 2009, 40:428-434.
- [11]Kim MK, Kim HS, Kim SH, Oh JM, Han JY, Lim JM, Juhnn YS, Song YS: Human papillomavirus type 16 E5 oncoprotein as a new target for cervical cancer treatment. Biochem Pharmacol 2010, 80:1930-1935.
- [12]Yamada T, Manos MM, Peto J, Greer CE, Munoz N, Bosch FX, Wheeler CM: Human papillomavirus type 16 sequence variation in cervical cancers: a worldwide perspective. J Virol Methods 1997, 71:2463-2472.
- [13]Huertas-Salgado A, Martin-Gamez DC, Moreno P, Murillo R, Bravo MM, Villa L, Molano M: E6 Molecular variants of human papillomavirus (HPV) type 16: an updated and unified criterion for clustering and nomenclature. Virology 2011, 410:201-215.
- [14]Hildesheim A, Schiffman M, Bromley C, Wacholder S, Herrero R, Rodriguez A, Bratti MC, Sherman ME, Scarpidis U, Lin QQ, et al.: Human papillomavirus type 16 variants and risk of cervical cancer. J Natl Cancer Inst 2001, 93:315-318.
- [15]Xi LF, Koutsky LA, Hildesheim A, Galloway DA, Wheeler CM, Winer RL, Ho J, Kiviat NB: Risk for high-grade cervical intraepithelial neoplasia associated with variants of human papillomavirus types 16 and 18. Cancer Epidemiol Biomarkers Prev 2007, 16:4-10.
- [16]Villa LL, Sichero L, Rahal P, Caballero O, Ferenczy A, Rohan T, Franco EL: Molecular variants of human papillomavirus types 16 and 18 preferentially associated with cervical neoplasia. J Gen Virol 2000, 81:2959-2968.
- [17]Berumen J, Ordonez RM, Lazcano E, Salmeron J, Galvan SC, Estrada RA, Yunes E, Garcia-Carranca A, Gonzalez-Lira G, Madrigal-de la Campa A: Asian-American variants of human papillomavirus 16 and risk for cervical cancer: a case–control study. J Natl Cancer Inst 2001, 93:1325-1330.
- [18]Li N, Franceschi S, Howell-Jones R, Snijders PJ, Clifford GM: Human papillomavirus type distribution in 30,848 invasive cervical cancers worldwide: variation by geographical region, histological type and year of publication. Int J Cancer 2010, 128:927-935.
- [19]Kammer C, Tommasino M, Syrjanen S, Delius H, Hebling U, Warthorst U, Pfister H, Zehbe I: Variants of the long control region and the E6 oncogene in European human papillomavirus type 16 isolates: implications for cervical disease. Br J Cancer 2002, 86:269-273.
- [20]Grodzki M, Besson G, Clavel C, Arslan A, Franceschi S, Birembaut P, Tommasino M, Zehbe I: Increased risk for cervical disease progression of French women infected with the human papillomavirus type 16 E6-350G variant. Cancer Epidemiol Biomarkers Prev 2006, 15:820-822.
- [21]Xi LF, Kiviat NB, Hildesheim A, Galloway DA, Wheeler CM, Ho J, Koutsky LA: Human papillomavirus type 16 and 18 variants: racerelated distribution and persistence. J Natl Cancer Inst 2006, 98:1045-1052.
- [22]Lee K, Magalhaes I, Clavel C, Briolat J, Birembaut P, Tommasino M, Zehbe I: Human papillomavirus 16 E6, L1, L2 and E2 gene variants in cervical lesion progression. Virus Res 2008, 131:106-110.
- [23]Burk RD, Terai M, Gravitt PE, Brinton LA, Kurman RJ, Barnes WA, Greenberg MD, Hadjimichael OC, Fu L, McGowan L, et al.: Distribution of human papillomavirus types 16 and 18 variants in squamous cell carcinomas and adenocarcinomas of the cervix. Cancer Res 2003, 63:7215-7220.
- [24]Zuna RE, Moore WE, Shanesmith RP, Dunn ST, Wang SS, Schiffman M, Blakey GL, Teel T: Association of HPV16 E6 variants with diagnostic severity in cervical cytology samples of 354 women in a US population. Int J Cancer 2009, 125:2609-2613.
- [25]Quint KD, de Koning MN, van Doorn LJ, Quint WG, Pirog EC: HPV genotyping and HPV16 variant analysis in glandular and squamous neoplastic lesions of the uterine cervix. Gynecol Oncol 2010, 117:297-301.
- [26]Schiffman M, Rodriguez AC, Chen Z, Wacholder S, Herrero R, Hildesheim A, Desalle R, Befano B, Yu K, Safaeian M, et al.: A population-based prospective study of carcinogenic human papillomavirus variant lineages, viral persistence, and cervical neoplasia. Cancer Res 2010, 70:3159-3169.
- [27]de Araujo Souza PS, Sichero L, Macia PC: HPV variants and HLA polymorphisms: the role of variability on the risk of cervical cancer. Future Oncol 2009, 5:359-370.
- [28]KrennHrubec K, Mrad K, Sriha B, Ben Ayed F, Bottalico DM, Ostolaza J, Smith B, Tchaikovska T, Soliman AS, Burk RD: HPV types and variants among cervical cancer tumors in three regions of Tunisia. J Med Virol 2011, 83:651-657.
- [29]Sambrook J, Fritsch EF, Maniatis T: Molecular cloning: a laboratory manual 2nd ed. NY’ Cold Spring Harbor Laboratory 1989, 1659. Press
- [30]Lee SH, Vigliotti VS, Vigliotti JS, Pappu S: Routine human papillomavirus genotyping by DNA sequencing in community hospital laboratories. Infect Agent Cancer 2007, 2:11. BioMed Central Full Text
- [31]Meftah El khair M, El Mzibri M, Mhand RA, Benider A, Benchekroun N, Fahime EM, Benchekroun MN, Ennaji MM: Molecular detection and genotyping of human papillomavirus in cervical carcinoma biopsies in an area of high incidence of cancer from Moroccan women. J Med Virol 2009, 81:678-684.
- [32]Tornesello ML, Losito S, Benincasa G, Fulciniti F, Botti G, Greggi S, Buonaguro L, Buonaguro FM: Human papillomavirus (HPV) genotypes and HPV16 variants and risk of adenocarcinoma and squamous cell carcinoma of the cervix. Gynecol Oncol 2011, 121:32-42.
- [33]Lee SH, Vigliotti VS, Vigliotti JS, Pappu S: Validation of human papillomavirus genotyping by signature DNA sequence analysis. BMC Clin Pathol 2009, 9:3. BioMed Central Full Text
- [34]Lizano M, De la Cruz-Hernandez E, Carrillo-Garcia A, Garcia-Carranca A, Ponce de Leon-Rosales S, Duenas-Gonzalez A, Hernandez-Hernandez DM, Mohar A: Distribution of HPV16 and 18 intratypic variants in normal cytology, intraepithelial lesions, and cervical cancer in a Mexican population. Gynecol Oncol 2006, 102:230-235.
- [35]Seedorf K, Krammer G, Durst M, Suhai S, Rowekamp WG: Human papillomavirus type 16 DNA sequence. Virology 1985, 145:181-185.
- [36]Munoz N, Bosch FX, de Sanjose S, Herrero R, Castellsague X, Shah KV, Snijders PJ, Meijer CJ: Epidemiologic classification of human papillomavirus types associated with cervical cancer. N Engl J Med 2003, 348:518-527.
- [37]Clifford GM, Smith JS, Aguado T, Franceschi S: Comparison of HPV type distribution in high-grade cervical lesions and cervical cancer: a meta-analysis. Br J Cancer 2003, 89:101-105.
- [38]de Sanjose S, Quint WG, Alemany L, Geraets DT, Klaustermeier JE, Lloveras B, Tous S, Felix A, Bravo LE, Shin HR, et al.: Human papillomavirus genotype attribution in invasive cervical cancer: a retrospective cross-sectional worldwide study. Lancet Oncol 2010, 11:1048-1056.
- [39]Zehbe I, Voglino G, Delius H, Wilander E, Tommasino M: Risk of cervical cancer and geographical variations of human papillomavirus 16 E6 polymorphisms. Lancet 1998, 352:1441-1442.
- [40]Pande S, Jain N, Prusty BK, Bhambhani S, Gupta S, Sharma R, Batra S, Das BC: 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 2008, 46:1060-1066.
- [41]Chan SY, Ho L, Ong CK, Chow V, Drescher B, Durst M, ter Meulen J, Villa L, Luande J, Mgaya HN, Bernard HU: Molecular variants of human papillomavirus type16 from four continents suggest ancient pandemic spread of the virus and its coevolution with humankind. J Virol 1992, 66:2057-2066.
- [42]Cornet I, Gheit T, Franceschi S, Vignat J, Burk RD, Sylla BS, Tommasino M, Clifford GM, the IARC HPV Variant Study Group: Human papillomavirus type 16 genetic variants: phylogeny and classification based on E6 and LCR. J Virol 2013, 86:6855-6861.
- [43]Pista A, Oliviera A, Barateiro A, Costa H, Verdasca N, Paixão : Molecular variants of human papillomavirus type 16 and 18 and risk for cervical neoplasia in Portugal. J Med Virol 2007, 79:1889-1897.
- [44]Tornesello ML, Duraturo ML, Salatiello I, Buonaguro L, Losito S, Botti G, Stellato G, Greggi S, Piccoli R, Pilotti S, et al.: Analysis of human papillomavirus type-16 variants in Italian women with cervical intraepithelial neoplasia and cervical cancer. J Med Virol 2004, 74:117-126.
- [45]Tu JJ, Kuhn L, Denny L, Beattie KJ, Lorincz A, Wright TC: Molecular variants of human papillomavirus type 16 and risk for cervical neoplasia in south Africa. Int J Gynecol Cancer 2006, 16:736-742.
- [46]Chopjitt P, Ekalaksananan T, Pientong C, Kongyingyoes B, Kleebkaow P, Charoensri N: Prevalence of human papillomavirus type 16 and its variants in abnormal squamous cervical cells in northeast Thailand. Int J Infect Dis 2009, 13:212-219.
- [47]Hu X, Guo Z, Tianyun P, Pont en F, Wilander E, Andersson S, Pont en J: HPV typing and HPV16 E6-sequence variations in synchronous lesions of cervical squamous-cell carcinoma from Swedish patients. Int J Cancer 1999, 83:34-37.
- [48]Sun M, Gao L, Liu Y, Zhao Y, Wang X, Pan Y, Ning T, Cai H, Yang H, Zhai W, Ke Y: Whole genome sequencing and evolutionary analysis of human papillomavirus type 16 in central China. PloS one 2012, 7:e36577.
- [49]Chakrabarti O, Veeraraghavalu K, Tergaonkar V, Liu Y, Androphy EJ, Stanley MA, Krishna S: Human papillomavirus type 16 E6 amino acid 83 variants enhance E6-mediated MAPK signaling and differentially regulate tumorigenesis by notch signaling and oncogenic Ras. J Virol 2004, 78:5934-5945.
- [50]van Duin M, Snijders PJ, Vossen MT, Klaassen E, Voorhorst F, Verheijen RH, Helmerhorst TJ, Meijer CJ, Walboomers JM: Analysis of human papillomavirus type 16 E6 variants in relation to p53 codon 72 polymorphism genotypes in cervical carcinogenesis. J Gen Virol 2000, 81:317-325.
- [51]Zehbe I, Richard C, DeCarlo CA, Shai A, Lambert PF, Lichtig H, Tommasino M, Sherman L: Human papillomavirus 16 E6 variants differ in their dysregulation of human keratinocyte differentiation and apoptosis. Virology 2009, 383:69-77.
- [52]Stöppler H, Koval D, Schlegel R: The serine protease inhibitors TLCK and TPCK inhibit the in vitro immortalization of primary human keratinocytes by HPV-18 DNA. Oncogene 1996, 13:1545-1548.
- [53]Wu Y, Chen Y, Li L, Yu G, He Y, Zhang Y: Analysis of mutations in the E6/E7 oncogenes and L1 gene of human papillomavirus 16 cervical cancer isolates from China. J Gen Virol 2006, 87:1181-1188.
- [54]Tonon SA, Basiletti J, Badano I, Alonio LV, Villa LL, Teyssie AR, Picconi MA: Human papillomavirus type 16 molecular variants in Guarani Indian women from Misiones, Argentina. Int J Infect Dis 2007, 11:76-81.
- [55]Picconi MA, Alonio LV, Sichero L, Mbayed V, Villa LL, Gronda J, Campos R, Teyssié A: Human papillomavirus type-16 variants in Quechua aboriginals from Argentina. J Med Virol 2003, 69:546-555.
- [56]DeFilippis RA, Goodwin EC, Wu L, DiMaio D: Endogenous human papillomavirus E6 and E7 proteins differentially regulate proliferation, senescence, and apoptosis in HeLa cervical carcinoma cells. J Virol 2003, 77:1551-1563.
- [57]Chen Z, Terai M, Fu L, Herrero R, DeSalle R, Burk RD: Diversifying selection in human papillomavirus type 16 lineages based on complete genome analyses. J Virol 2005, 79:7014-7023.
- [58]Zehbe I, Mytilineos J, Wikström I, Henriksen R, Edler L, Tommasino M: Association between human papillomavirus 16 E6 variants and human leukocyte antigen class I polymorphism in cervical cancer of Swedish women. Hum Immunol 2003, 64:538-542.
- [59]Ellis JR JKP, Baird J, Hounsell EF VRD, Rowe M, Hopkins D, Duggan-Keen MF, Bartholomew JS, Young LS: The association of an HPV16 oncogene variant with HLA-B7 has implications for vaccine design in cervical cancer. Nat Med 1995, 1:464-470.
- [60]Bartholomew JS, Stacey SN, Coles B, Burt DJ, Arrand JR, Stern PL: Identification of a naturally processed HLA A0201-restricted viral peptide from cells expressing human papillomavirus type 16 E6 oncoprotein. Eur J Immunol 1994, 24:3175-3179.