HPV prevalence and genotype distribution in a population-based split-sample study of well-screened women using CLART HPV2 Human Papillomavirus genotype microarray system

BMC Infectious Diseases

Carsten Rygaard²  Elsebeth Lynge¹  Sarah Preisler³  Ditte Møller Ejegod³  Matejka Rebolj¹  Jesper Bonde³ 

[1] Department of Public Health, University of Copenhagen, Øster Farimagsgade 5, 1014 Copenhagen K, Denmark;Department of Pathology, Copenhagen University Hospital, Hvidovre, Kettegård Allé 30, 2650 Hvidovre, Denmark;Clinical Research Center, Copenhagen University Hospital, Hvidovre, Kettegård Allé 30, 2650 Hvidovre, Denmark

关键词: Vaccine monitoring;    HC2;    CLART;    Assay;    Screening;    Genotyping;    Cervical cancer;    Human papillomavirus;   

Others  :  1127284
DOI  :  10.1186/1471-2334-14-413

 received in 2013-12-06, accepted in 2014-07-22,  发布年份 2014

【 摘 要 】

Background

Human papillomavirus (HPV) genotyping assays are becoming increasingly attractive for use in mass screening, as they offer a possibility to integrate HPV screening with HPV vaccine monitoring, thereby generating a synergy between the two main modes of cervical cancer prevention. The Genomica CLART HPV2 assay is a semi-automated PCR-based microarray assay detecting 35 high-risk and low-risk HPV genotypes. However, few reports have described this assay in cervical screening.

An aim of the present study, Horizon, was to assess the prevalence of high-risk HPV infections in Copenhagen, Denmark, an area with a high background risk of cervical cancer where women aged 23-65 years are targeted for organized screening.

Methods

Material from 5,068 SurePath samples of women participating in routine screening and clinical follow-up of cervical abnormalities was tested using liquid based cytology, CLART HPV2 and Hybrid Capture 2 (HC2).

Results

At least one of the 35 defined genotypes was detected by CLART in 1,896 (37%) samples. The most frequent high-risk genotypes were HPV 16 (7%), HPV 52 (5%), and HPV 31 (4%). The most frequent low-risk genotypes were HPV 53 (5%), HPV 61 (4%), and HPV 66 (3%). Among 4,793 women targeted by the screening program (23-65 years), 1,166 (24%) tested positive for one or more of the 13 high-risk genotypes. This proportion decreased from 40% at age 23-29 years to 10% at age 60-65 years. On HC2, 1,035 (20%) samples were positive for any high-risk and thus CLART showed a higher analytical sensitivity for 13 high-risk HPV genotypes than HC2, and this was found in all age-groups and in women normal cytology.

Conclusions

CLART performed well with a positive reproducibility for high-risk genotypes of 86%, and a negative reproducibility of 97%. This report furthermore updates the genotype distribution in Denmark prior to the inclusion of the HPV-vaccinated cohorts into the screening program, and as such represents a valuable baseline for future vaccine impact assessment.

【 授权许可】

   
2014 Bonde et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

【 参考文献 】

• [1]Walboomers JM, Jacobs MV, Manos MM, Bosch FX, Kummer JA, Shah KV, Snijders PJ, Peto J, Meijer CJ, Muñoz N: Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol 1999, 189:12-19.
• [2]Bouvard V, Baan R, Straif K, Grosse Y, Secretan B, El Ghissassi F, Benbrahim-Tallaa L, Guha N, Freeman C, Galichet L, Cogliano V, WHO International Agency for Research on Cancer Monograph Working Group: A review of human carcinogens–Part B: biological agents. Lancet Oncol 2009, 10:321-322.
• [3]Rijkaart DC, Berkhof J, Rozendaal L, van Kemenade FJ, Bulkmans NW, Heideman DA, Kenter GG, Cuzick J, Snijders PJ, Meijer CJ: Human papillomavirus testing for the detection of high-grade cervical intraepithelial neoplasia and cancer: final results of the POBASCAM randomised controlled trial. Lancet Oncol 2012, 13:78-88.
• [4]Ronco G, Giorgi-Rossi P, Carozzi F, Confortini M, Dalla Palma P, Del Mistro A, Ghiringhello B, Girlando S, Gillio-Tos A, De Marco L, Naldoni C, Pierotti P, Rizzolo R, Schincaglia P, Zorzi M, Zappa M, Segnan N, Cuzick J, New Technologies for Cervical Cancer screening (NTCC) Working Group: Efficacy of human papillomavirus testing for the detection of invasive cervical cancers and cervical intraepithelial neoplasia: a randomised controlled trial. Lancet Oncol 2010, 11:249-257.
• [5]Franco EL, Cuzick J, Hildesheim A, de Sanjose S: Chapter 20: Issues in planning cervical cancer screening in the era of HPV vaccination. Vaccine 2006, 24(Suppl 3):171-177.
• [6]Kaspersen MD, Larsen PB, Ingerslev HJ, Fedder J, Petersen GB, Bonde J, Höllsberg P: Identification of multiple HPV types on spermatozoa from human sperm donors. PLoS One 2011, 6:e18095.
• [7]Galan-Sanchez F, Rodriguez-Iglesias MA: Comparison of human papillomavirus genotyping using commercial assays based on PCR and reverse hybridization methods. APMIS 2009, 117:708-715.
• [8]Mejlhede N, Bonde J, Fomsgaard A: High frequency of multiple HPV types in cervical specimens from Danish women. APMIS 2009, 117:108-114.
• [9]Szarewski A, Ambroisine L, Cadman L, Austin J, Ho L, Terry G, Liddle S, Dina R, McCarthy J, Buckley H, Bergeron C, Soutter P, Lyons D, Cuzick J: Comparison of predictors for high-grade cervical intraepithelial neoplasia in women with abnormal smears. Cancer Epidemiol Biomarkers Prev 2008, 17:3033-3042.
• [10]García-Sierra N, Martró E, Castellà E, Llatjós M, Tarrats A, Bascuñana E, Díaz R, Carrasco M, Sirera G, Matas L, Ausina V: Evaluation of an array-based method for human papillomavirus detection and genotyping in comparison with conventional methods used in cervical cancer screening. J Clin Microbiol 2009, 47:2165-2169.
• [11]Chranioti A, Spathis A, Aga E, Meristoudis C, Pappas A, Panayiotides I, Karakitsos P: Comparison of two commercially available methods for HPV genotyping: CLART HPV2 and Linear Array HPV Genotyping tests. Anal Quant Cytol Histol 2012, 34:257-263.
• [12]Pista A, Verdasca N, Oliveira A: Clinical performance of the CLART human papillomavirus 2 assay compared with the hybrid capture 2 test. J Med Virol 2011, 83:272-276.
• [13]Valasoulis G, Koliopoulos G, Founta C, Kyrgiou M, Tsoumpou I, Valari O, Martin-Hirsch P, Daponte A, Karakitsos P, Paraskevaidis E: Alterations in human papillomavirus-related biomarkers after treatment of cervical intraepithelial neoplasia. Gynecol Oncol 2011, 121:43-48.
• [14]Arbyn M, Roelens J, Cuschieri K, Cuzick J, Szarewski A, Ratnam S, Reuschenbach M, Belinson S, Belinson JL, Monsonego J: The APTIMA HPV assay versus the hybrid capture 2 test in triage of women with ASC-US or LSIL cervical cytology: A meta-analysis of the diagnostic accuracy. Int J Cancer 2013, 132:101-108.
• [15]Kjaer SK, Breugelmans G, Munk C, Junge J, Watson M, Iftner T: Population-based prevalence, type- and age-specific distribution of HPV in women before introduction of an HPV-vaccination program in Denmark. Int J Cancer 2008, 123:1864-1870.
• [16]Clemmesen J, Nielsen A: The social distribution of cancer in Copenhagen, 1943 to 1947. Br J Cancer 1951, 5:159-171.
• [17]Styregruppen for DKLS: Årsrapport DKLS 2012: Dansk Kvalitetsdatabase for Livmoderhalskræftscreening [Annual report 2012: Danish Quality Assurance database for cervical cancer screening]. Hvidovre: DKLS; 2013.
• [18]Rebolj M, Preisler S, Ejegod DM, Bonde J, Rygaard C, Lynge E: Prevalence of human papillomavirus infection in unselected SurePath samples using the APTIMA HPV mRNA assay. J Mol Diagn 2013, 15:670-677.
• [19]Preisler S, Rebolj M, Untermann A, Ejegod DM, Lynge E, Rygaard C, Bonde J: Prevalence of human papillomavirus in 5,072 consecutive cervical SurePath samples evaluated with the Roche cobas HPV real-time PCR assay. PLoS One 2013, 8:e59765.
• [20]Goldman B, Rebolj M, Rygaard C, Preisler S, Ejegod DM, Lynge E, Bonde J: Patterns of cervical coinfection with multiple human papilloma virus types in a screening population in Denmark. Vaccine 2013, 31:1604-1609.
• [21]Bjerregaard B, Larsen OB: The Danish pathology register. Scand J Public Health 2011, 39(Suppl 7):72-74.
• [22]Muñoz N, Bosch FX, Castellsagué X, Díaz M, de Sanjose S, Hammouda D, Shah KV, Meijer CJ: Against which human papillomavirus types shall we vaccinate and screen? The international perspective. Int J Cancer 2004, 111:278-285.
• [23]Pista A, de Oliveira CF, Cunha MJ, Paixao MT, Real O: Risk factors for human papillomavirus infection among women in Portugal: The CLEOPATRE Portugal Study. Int J Gynaecol Obstet 2012, 118:112-116.
• [24]Pista A, de Oliveira CF, Cunha MJ, Paixao MT, Real O: Prevalence of human papillomavirus infection in women in Portugal: the CLEOPATRE Portugal study. Int J Gynecol Cancer 2011, 21:1150-1158.
• [25]Dutra I, Santos MR, Soares M, Couto AR, Bruges-Armas M, Teixeira F, Monjardino L, Hodgson S, Bruges-Armas J: Characterisation of human papillomavirus (HPV) genotypes in the Azorean population, Terceira island. Infect Agent Cancer 2008, 3:6. BioMed Central Full Text
• [26]Mejlhede N, Pedersen BV, Frisch M, Fomsgaard A: Multiple human papilloma virus types in cervical infections: competition or synergy? APMIS 2010, 118:346-352.
• [27]Szarewski A, Sasieni P: Cervical screening in adolescents–at least do no harm. Lancet 2004, 364:1642-1644.
• [28]Cuzick J, Arbyn M, Sankaranarayanan R, Tsu V, Ronco G, Mayrand MH, Dillner J, Meijer CJ: Overview of human papillomavirus-based and other novel options for cervical cancer screening in developed and developing countries. Vaccine 2008, 26(Suppl 10):29-41.
• [29]Barken SS, Rebolj M, Andersen ES, Lynge E: Frequency of cervical intraepithelial neoplasia treatment in a well-screened population. Int J Cancer 2012, 130:2438-2444.
• [30]Cox JT, Castle PE, Behrens CM, Sharma A, Wright TC Jr, Cuzick J: Comparison of cervical cancer screening strategies incorporating different combinations of cytology, HPV testing, and genotyping for HPV 16/18: results from the ATHENA HPV study. Am J Obstet Gynecol 2013, 208:184.
• [31]Coupe VM, Bogaards JA, Meijer CJ, Berkhof J: Impact of vaccine protection against multiple HPV types on the cost-effectiveness of cervical screening. Vaccine 2012, 30:1813-1822.