title: Comparison of Hybrid capture 2 testing at different thresholds with cytology as primary cervical screening test.
abstract: BACKGROUND
  We evaluated the performance of primary high-risk human papillomavirus (hrHPV) testing by hybrid capture 2 (HC2) with different thresholds for positivity, in comparison with conventional cytology.
  
  
  METHODS
  We used data of 25,871 women (aged 30-60 years) from the intervention group of the VUSA-Screen study (VU University Medical Center and Saltro laboratory population-based cervical screening study), who were screened by cytology and hrHPV. Primary outcome measure was the number of cervical intraepithelial neoplasia grade 3 or higher (CIN3+), detected within 3 years. We compared baseline cytology testing with three possible hrHPV screening strategies at different relative light unit/cutoff (RLU/CO) thresholds.
  
  
  RESULTS
  Compared with baseline cytology testing, hrHPV DNA testing as a sole primary screening instrument did not yield a superior sensitivity, as well as lower colposcopy referral rate and lower false positivity rate at any RLU/CO threshold. The hrHPV screening at 1 RLU/CO threshold with cytology triage at baseline and at 12 months revealed the highest sensitivity for CIN3+ (relative sensitivity of 1.32), although still displaying a lower colposcopy referral rate than cytology testing (relative colposcopy rate of 0.94). Higher thresholds (>1 RLU/CO) yielded lower colposcopy rates, but resulted in substantial loss in sensitivity.
  
  
  CONCLUSIONS
  The hrHPV testing at the commonly used threshold of 1 RLU/CO with cytology triage at baseline and at 12 months showed a much higher sensitivity with a lower colposcopy referral rate compared with cytology testing.
authors.affiliation: Department of Pathology, VU University Medical Center, P.O. Box 7057, Amsterdam 1007 MB, The Netherlands.
authors.forename: D C
authors.initials: DC
authors.lastname: Rijkaart
authors.forename: V M H
authors.initials: VM
authors.lastname: Coupe
authors.forename: F J
authors.initials: FJ
authors.lastname: van Kemenade
authors.forename: D A M
authors.initials: DA
authors.lastname: Heideman
authors.forename: A T
authors.initials: AT
authors.lastname: Hesselink
authors.forename: W
authors.initials: W
authors.lastname: Verweij
authors.forename: L
authors.initials: L
authors.lastname: Rozendaal
authors.forename: R H
authors.initials: RH
authors.lastname: Verheijen
authors.forename: P J
authors.initials: PJ
authors.lastname: Snijders
authors.forename: J
authors.initials: J
authors.lastname: Berkhof
authors.forename: C J L M
authors.initials: CJ
authors.lastname: Meijer
mesh_terms: D000328:Adult; D003127:Colposcopy; D055088:Early Detection of Cancer; D005189:False Positive Reactions; D005260:Female; D006801:Humans; D008875:Middle Aged; D009693:Nucleic Acid Hybridization; D030361:Papillomavirus Infections / Q000175:diagnosis*; D012017:Referral and Consultation; D012680:Sensitivity and Specificity; D014218:Triage; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000382:microbiology; D014626:Vaginal Smears; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis* / Q000382:microbiology
references.citation: Lancet. 2009 Jul 25;374(9686):301-14
references.pmid: 19586656
references.citation: J Clin Pathol. 2004 Apr;57(4):388-93
references.pmid: 15047743
references.citation: J Natl Cancer Inst. 2006 Jun 7;98(11):765-74
references.pmid: 16757701
references.citation: Vaccine. 2006 Aug 31;24 Suppl 3:S3/171-7
references.pmid: 16844268
references.citation: J Pathol. 2009 Nov;219(3):327-36
references.pmid: 19662663
references.citation: Lancet. 2006 Apr 15;367(9518):1247-55
references.pmid: 16631880
references.citation: Cancer Epidemiol Biomarkers Prev. 2005 Mar;14(3):677-86
references.pmid: 15767349
references.citation: Lancet Oncol. 2010 Mar;11(3):249-57
references.pmid: 20089449
references.citation: JAMA. 2002 Oct 9;288(14):1749-57
references.pmid: 12365959
references.citation: Br J Cancer. 2005 Oct 17;93(8):862-7
references.pmid: 16189520
references.citation: JAMA. 2000 Jan 5;283(1):87-93
references.pmid: 10632285
references.citation: N Engl J Med. 2007 Oct 18;357(16):1579-88
references.pmid: 17942871
references.citation: BMJ. 2009 Jul 28;339:b3005
references.pmid: 19638652
references.citation: Int J Cancer. 2006 Sep 1;119(5):1095-101
references.pmid: 16586444
references.citation: BJOG. 2000 May;107(5):600-4
references.pmid: 10826572
references.citation: Biometrics. 1983 Mar;39(1):207-15
references.pmid: 6871349
references.citation: Lancet. 2007 Nov 24;370(9601):1764-72
references.pmid: 17919718
references.citation: J Clin Pathol. 2002 Apr;55(4):244-65
references.pmid: 11919208
references.citation: Lancet Oncol. 2006 Jul;7(7):547-55
references.pmid: 16814206
references.citation: Biostatistics. 2001 Sep;2(3):249-60
references.pmid: 12933537
references.citation: J Clin Microbiol. 2010 Feb;48(2):554-8
references.pmid: 20007387
references.citation: Vaccine. 2006 Aug 31;24 Suppl 3:S3/78-89
references.pmid: 16950021
references.citation: J Med Virol. 2004 May;73(1):65-70
references.pmid: 15042650
references.citation: Int J Cancer. 2008 Dec 15;123(12):2902-6
references.pmid: 18792100
references.citation: N Engl J Med. 2007 Oct 18;357(16):1589-97
references.pmid: 17942872
references.citation: Obstet Gynecol. 2004 Feb;103(2):304-9
references.pmid: 14754700
references.citation: J Natl Cancer Inst. 2008 Apr 2;100(7):492-501
references.pmid: 18364502
references.citation: J Natl Cancer Inst. 2009 Dec 2;101(23):1612-23
references.pmid: 19903804
references.citation: N Engl J Med. 2003 Feb 6;348(6):518-27
references.pmid: 12571259
references.citation: J Natl Cancer Inst. 2000 May 17;92(10):818-25
references.pmid: 10814677
references.citation: Int J Cancer. 2009 Feb 1;124(3):516-20
references.pmid: 18973271
references.citation: J Pathol. 2008 Aug;215(4):388-97
references.pmid: 18498117
references.citation: Int J Cancer. 2010 Nov 1;127(9):2147-58
references.pmid: 20112339
references.citation: Lancet Oncol. 2008 Oct;9(10):937-45
references.pmid: 18783988
references.citation: Br J Cancer. 2001 Jun 15;84(12):1616-23
references.pmid: 11401314
references.citation: J Clin Microbiol. 2006 Oct;44(10):3680-5
references.pmid: 17021097
references.citation: Int J Cancer. 2007 Jul 15;121(2):361-7
references.pmid: 17354241
references.citation: Ann Intern Med. 2000 May 16;132(10):810-9
references.pmid: 10819705
references.citation: Cancer Epidemiol Biomarkers Prev. 2005 Feb;14(2):367-72
references.pmid: 15734959
references.citation: J Clin Microbiol. 2004 Jun;42(6):2470-5
references.pmid: 15184422
references.citation: Int J Cancer. 2010 May 1;126(9):2175-81
references.pmid: 19739071
references.citation: J Natl Cancer Inst. 2009 Jan 21;101(2):88-99
references.pmid: 19141778
references.citation: Lancet. 2006 Feb 11;367(9509):489-98
references.pmid: 16473126
references.citation: Vaccine. 2009 Aug 13;27(37):5111-9
references.pmid: 19567242
references.citation: Lancet. 2009 Dec 12;374(9706):1975-85
references.pmid: 19962185
references.citation: J Pathol. 1999 Sep;189(1):12-9
references.pmid: 10451482
references.citation: Lancet Oncol. 2009 Jul;10(7):672-82
references.pmid: 19540162
references.citation: J Natl Cancer Inst. 2008 Mar 5;100(5):308-20
references.pmid: 18314477
references.citation: N Engl J Med. 2007 May 10;356(19):1915-27
references.pmid: 17494925
references.citation: Vaccine. 2008 Aug 19;26 Suppl 10:K29-41
references.pmid: 18847555