Abstract
Most cervical cancers are caused by 15 high-risk (HR) and three probable high-risk (pHR) oncogenic types of human papillomavirus (HPV). However, current commercial HR HPV screening test products do not include pHR HPV genotypes. Recently, PapilloScreen has been developed to detect the 15 HR and three pHR HPV types. In this study, we evaluated the concordance levels and clinical performance of Hybrid Capture 2 (HC2), PapilloScreen, and a PCR sequencing assay in detecting HR and pHR HPV. The PapilloScreen (96.8 %) and PCR sequencing assay (96.8 %) demonstrated higher sensitivity than HC2 (80.7 %) for detecting HR and pHR HPV. The three assays showed similar specificities and positive or negative predictive values. The concordance levels were 86.5 % (κ = 0.68) and 86.5 % (κ = 0.67) between HC2 and PapilloScreen and between HC2 and PCR sequencing, respectively. A near-perfect concordance was observed between PapilloScreen and PCR sequencing (97.8 %, κ = 0.95). Overall, the agreement between the three assays suggests that the results obtained by the HC2 assay are more often discordant (12.6 %) than the PCR-based tests. In conclusion, PapilloScreen is highly sensitive for detecting high-grade CIN or cervical cancer. The PapilloScreen assay should be considered an accurate and sensitive method for detecting HR and pHR HPV infections and an epidemiological tool for prevalence studies as well as early diagnosis and intervention in HR and pHR HPV infections.
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References
Bosch FX, Manos MM, Munoz N, Sherman M, Jansen AM, Peto J, Schiffman MH, Moreno V, Kurman R, Shah KV (1995) Prevalence of human papillomavirus in cervical cancer: a worldwide perspective. International biological study on cervical cancer (IBSCC) Study Group. J Natl Cancer Inst 87(11):796–802
Kim YT (2009) Current status of cervical cancer and HPV infection in Korea. J Gynecol Oncol 20(1):1–7. doi:10.3802/jgo.2009.20.1.1
Shin HR, Jung KW, Won YJ, Kong HJ, Yim SH, Sung J, Seo SW, Kim KY, Lee SY, Kong IS, Hwang IK, Lee CW, Woo ZH, Lee TY, Choi JS, Yoo CI, Bae JM, Yoo KY (2007) National cancer incidence for the year 2002 in Korea. Cancer Res Treat : Off J Korean Cancer Assoc 39(4):139–149. doi:10.4143/crt.2007.39.4.139
Nanda K, McCrory DC, Myers ER, Bastian LA, Hasselblad V, Hickey JD, Matchar DB (2000) Accuracy of the Papanicolaou test in screening for and follow-up of cervical cytologic abnormalities: a systematic review. Ann Internal Med 132(10):810–819
zur Hausen H (1994) Molecular pathogenesis of cancer of the cervix and its causation by specific human papillomavirus types. Curr Top Microbiol Immunol 186:131–156
Walboomers JM, Jacobs MV, Manos MM, Bosch FX, Kummer JA, Shah KV, Snijders PJ, Peto J, Meijer CJ, Munoz N (1999) Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol 189(1):12–19. doi:10.1002/(SICI)1096-9896(199909)189:1<12::AID-PATH431>3.0.CO;2-F
Munoz N, Bosch FX, de Sanjose S, Herrero R, Castellsague X, Shah KV, Snijders PJ, Meijer CJ, International Agency for Research on Cancer Multicenter Cervical Cancer Study G (2003) Epidemiologic classification of human papillomavirus types associated with cervical cancer. N Engl J Med 348(6):518–527. doi:10.1056/NEJMoa021641
Lee HP, Kim SO, Hwang TS, Bae JM, Kim SN, Kim JW, Hwang SY, Lee HS, Shin SK, Cho W, Hong SP (2011) Analytical and clinical performances of a restriction fragment mass polymorphism assay for detection and genotyping of a wide spectrum of human papillomaviruses. J Med Virol 83(3):471–482. doi:10.1002/jmv.21992
Li N, Franceschi S, Howell-Jones R, Snijders PJ, Clifford GM (2011) Human papillomavirus type distribution in 30,848 invasive cervical cancers worldwide: Variation by geographical region, histological type and year of publication. Int J Cancer 128(4):927–935. doi:10.1002/ijc.25396
Bulkmans NW, Rozendaal L, Voorhorst FJ, Snijders PJ, Meijer CJ (2005) Long-term protective effect of high-risk human papillomavirus testing in population-based cervical screening. Br J Cancer 92(9):1800–1802. doi:10.1038/sj.bjc.6602541
Clavel C, Cucherousset J, Lorenzato M, Caudroy S, Nou JM, Nazeyrollas P, Polette M, Bory JP, Gabriel R, Quereux C, Birembaut P (2004) Negative human papillomavirus testing in normal smears selects a population at low risk for developing high-grade cervical lesions. Br J Cancer 90(9):1803–1808. doi:10.1038/sj.bjc.6601726
Lorincz AT, Reid R, Jenson AB, Greenberg MD, Lancaster W, Kurman RJ (1992) Human papillomavirus infection of the cervix: relative risk associations of 15 common anogenital types. Obstet Gynecol 79(3):328–337
Poljak M, Brencic A, Seme K, Vince A, Marin IJ (1999) Comparative evaluation of first- and second-generation digene hybrid capture assays for detection of human papillomaviruses associated with high or intermediate risk for cervical cancer. J Clin Microbiol 37(3):796–797
Burd EM (2003) Human papillomavirus and cervical cancer. Clin Microbiol Rev 16(1):1–17
Vince A, Kutela N, Iscic-Bes J, Harni V, Ivanisevic M, Sonicki Z, Culig Z, Poljak M (2002) Clinical utility of molecular detection of human papillomavirus in cervical samples by hybrid capture technology. J Clin Virol: Off Publ Pan Am Soc Clin Virol 25(Suppl 3):S109–S112
Castle PE, Lorincz AT, Mielzynska-Lohnas I, Scott DR, Glass AG, Sherman ME, Schussler JE, Schiffman M (2002) Results of human papillomavirus DNA testing with the hybrid capture 2 assay are reproducible. J Clin Microbiol 40(3):1088–1090
Peyton CL, Schiffman M, Lorincz AT, Hunt WC, Mielzynska I, Bratti C, Eaton S, Hildesheim A, Morera LA, Rodriguez AC, Herrero R, Sherman ME, Wheeler CM (1998) Comparison of PCR- and hybrid capture-based human papillomavirus detection systems using multiple cervical specimen collection strategies. J Clin Microbiol 36(11):3248–3254
Poljak M, Marin IJ, Seme K, Vince A (2002) Hybrid Capture II HPV Test detects at least 15 human papillomavirus genotypes not included in its current high-risk probe cocktail. J Clin Virol: Off Publ Pan Am Soc Clin Virol 25(Suppl 3):S89–S97
Terry G, Ho L, Londesborough P, Cuzick J, Mielzynska-Lohnas I, Lorincz A (2001) Detection of high-risk HPV types by the hybrid capture 2 test. J Med Virol 65(1):155–162
Schneede P, Hillemanns P, Ziller F, Hofstetter A, Stockfleth E, Arndt R, Meyer T (2001) Evaluation of HPV testing by Hybrid Capture II for routine gynecologic screening. Acta obstetricia et gynecologica Scandinavica 80(8):750–752
Solomon D, Davey D, Kurman R, Moriarty A, O’Connor D, Prey M, Raab S, Sherman M, Wilbur D, Wright T Jr, Young N (2002) The 2001 Bethesda System: terminology for reporting results of cervical cytology. JAMA : J Am Med Assoc 287(16):2114–2119
Gravitt PE, Peyton CL, Alessi TQ, Wheeler CM, Coutlee F, Hildesheim A, Schiffman MH, Scott DR, Apple RJ (2000) Improved amplification of genital human papillomaviruses. J Clin Microbiol 38(1):357–361
Shin HR, Lee DH, Herrero R, Smith JS, Vaccarella S, Hong SH, Jung KY, Kim HH, Park UD, Cha HS, Park S, Touze A, Munoz N, Snijders PJ, Meijer CJ, Coursaget P, Franceschi S (2003) Prevalence of human papillomavirus infection in women in Busan, South Korea. Int J Cancer 103(3):413–421. doi:10.1002/ijc.10825
Sukvirach S, Smith JS, Tunsakul S, Munoz N, Kesararat V, Opasatian O, Chichareon S, Kaenploy V, Ashley R, Meijer CJ, Snijders PJ, Coursaget P, Franceschi S, Herrero R (2003) Population-based human papillomavirus prevalence in Lampang and Songkla, Thailand. J Infect Dis 187(8):1246–1256. doi:10.1086/373901
Pham TH, Nguyen TH, Herrero R, Vaccarella S, Smith JS, Nguyen Thuy TT, Nguyen HN, Nguyen BD, Ashley R, Snijders PJ, Meijer CJ, Munoz N, Parkin DM, Franceschi S (2003) Human papillomavirus infection among women in South and North Vietnam. Int J Cancer 104(2):213–220. doi:10.1002/ijc.10936
American College of Obstetricians and Gynecologists (2008) ACOG Practice Bulletin No. 99: management of abnormal cervical cytology and histology. Obstet Gynecol 112(6):1419–1444. doi:10.1097/AOG.0b013e318192497c
Schiffman M, Castle PE, Jeronimo J, Rodriguez AC, Wacholder S (2007) Human papillomavirus and cervical cancer. Lancet 370(9590):890–907. doi:10.1016/S0140-6736(07)61416-0
Stevens MP, Garland SM, Rudland E, Tan J, Quinn MA, Tabrizi SN (2007) Comparison of the Digene Hybrid Capture 2 assay and Roche AMPLICOR and LINEAR ARRAY human papillomavirus (HPV) tests in detecting high-risk HPV genotypes in specimens from women with previous abnormal Pap smear results. J Clin Microbiol 45(7):2130–2137. doi:10.1128/JCM.02438-06
Tsiodras S, Georgoulakis J, Chranioti A, Voulgaris Z, Psyrri A, Tsivilika A, Panayiotides J, Karakitsos P (2010) Hybrid capture vs. PCR screening of cervical human papilloma virus infections. Cytological and histological associations in 1270 women. BMC cancer 10:53. doi:10.1186/1471-2407-10-53
Poljak M, Ostrbenk A, Seme K, Ucakar V, Hillemanns P, Bokal EV, Jancar N, Klavs I (2011) Comparison of clinical and analytical performance of the Abbott Realtime High Risk HPV test to the performance of hybrid capture 2 in population-based cervical cancer screening. J Clin Microbiol 49(5):1721–1729. doi:10.1128/JCM.00012-11
Fontaine V, Mascaux C, Weyn C, Bernis A, Celio N, Lefevre P, Kaufman L, Garbar C (2007) Evaluation of combined general primer-mediated PCR sequencing and type-specific PCR strategies for determination of human papillomavirus genotypes in cervical cell specimens. J Clin Microbiol 45(3):928–934. doi:10.1128/JCM.02098-06
Castle PE, Solomon D, Wheeler CM, Gravitt PE, Wacholder S, Schiffman M (2008) Human papillomavirus genotype specificity of hybrid capture 2. J Clin Microbiol 46(8):2595–2604. doi:10.1128/JCM.00824-08
Sandri MT, Lentati P, Benini E, Dell’Orto P, Zorzino L, Carozzi FM, Maisonneuve P, Passerini R, Salvatici M, Casadio C, Boveri S, Sideri M (2006) Comparison of the Digene HC2 assay and the Roche AMPLICOR human papillomavirus (HPV) test for detection of high-risk HPV genotypes in cervical samples. J Clin Microbiol 44(6):2141–2146. doi:10.1128/JCM.00049-06
Safaeian M, Herrero R, Hildesheim A, Quint W, Freer E, Van Doorn LJ, Porras C, Silva S, Gonzalez P, Bratti MC, Rodriguez AC, Castle P, Costa Rican Vaccine Trial G (2007) Comparison of the SPF10-LiPA system to the Hybrid Capture 2 Assay for detection of carcinogenic human papillomavirus genotypes among 5,683 young women in Guanacaste, Costa Rica. J Clin Microbiol 45(5):1447–1454. doi:10.1128/JCM.02580-06
Koliopoulos G, Valasoulis G, Zilakou E (2009) An update review on HPV testing methods for cervical neoplasia. Expert Opin Med Diagn 3(2):123–131. doi:10.1517/17530050802705680
Mayrand MH, Duarte-Franco E, Rodrigues I, Walter SD, Hanley J, Ferenczy A, Ratnam S, Coutlee F, Franco EL, Canadian Cervical Cancer Screening Trial Study G (2007) Human papillomavirus DNA versus Papanicolaou screening tests for cervical cancer. N Engl J Med 357(16):1579–1588. doi:10.1056/NEJMoa071430
Molden T, Kraus I, Skomedal H, Nordstrom T, Karlsen F (2007) PreTect HPV-Proofer: real-time detection and typing of E6/E7 mRNA from carcinogenic human papillomaviruses. J Virol Methods 142(1-2):204–212. doi:10.1016/j.jviromet.2007.01.036
Benevolo M, Vocaturo A, Caraceni D, French D, Rosini S, Zappacosta R, Terrenato I, Ciccocioppo L, Frega A, Giorgi Rossi P (2011) Sensitivity, specificity, and clinical value of human papillomavirus (HPV) E6/E7 mRNA assay as a triage test for cervical cytology and HPV DNA test. J Clin Microbiol 49(7):2643–2650. doi:10.1128/JCM.02570-10
Acknowledgments
This work was supported by the Converging Research Center Program through the Ministry of Science, ICT and Future Planning (2013K000428).
Conflict of interest
Kyung Tae Min, Ji Young Shin, Soo-Kyung Shin, Soo Ok Kim, and Sun Pyo Hong are employees of GeneMatrix Inc. Jae-Man Bae, So Nyung Kim, and Hyo-Pyo Lee have nothing to declare.
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J.-M. Bae and K. T. Min contributed equally.
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705_2014_2020_MOESM1_ESM.jpg
Supplemental Figure 1. Schematic illustration of primer design for PapilloScreen. PapilloScreen consists of multiple primer sets within a single PCR mixture that are specific for DNA sequences in different genes: E1, E2, E4, E5, E6, E7, L1, and L2. (JPEG 42 kb)
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Bae, JM., Min, K.T., Shin, J.Y. et al. Comparison of Digene Hybrid Capture 2, GeneMatrix PapilloScreen, and a PCR sequencing assay in detecting high-risk and probable high-risk oncogenic HPV genotypes in specimens from Korean women. Arch Virol 159, 1909–1916 (2014). https://doi.org/10.1007/s00705-014-2020-8
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DOI: https://doi.org/10.1007/s00705-014-2020-8