title: Comparison of GP5+/6+-PCR and SPF10-line blot assays for detection of high-risk human papillomavirus in samples from women with normal cytology results who develop grade 3 cervical intraepithelial neoplasia.
abstract: Using a case control approach, we performed a two-way comparison study between GP5+/6+-PCR and HPV SPF(10)-Line Blot 25 (SPF(10)) assays for detection of 14 types of high-risk human papillomavirus (hrHPV) in samples from women with normal cytology results who had or developed grade 3 cervical intraepithelial neoplasia (CIN 3). Samples were pooled from two cohorts, i.e., women participating in population-based screening and women attending a gynecological outpatient clinic. Cases (n = 45) were women with histologically confirmed CIN 3 diagnosed within a median follow-up time of 2.7 (range, 0.2 to 7.9) years. Control samples were from women (n = 264) who had developed CIN 1 lesions at maximum (median follow-up at 5.8 [range, 0 to 10] years). Identical numbers of cases tested positive for 1 or more of the 14 hrHPV types by both systems (40/45; McNemar; P = 1.0). Conversely, SPF(10) scored significantly more controls as hrHPV positive than did GP5+/6+-PCR (95/264 versus 29/264; McNemar; P < 0.001). Consequently, women with normal cytology results and an hrHPV GP5+/6+-PCR-positive test exhibited a risk of CIN 3 that was 4.5 times higher (odds ratio [OR], 65; 95% confidence interval [95%CI], 24 to 178) than that seen for women with an hrHPV-positive SPF(10) test (OR, 14; 95%CI, 5 to 38)). Similar results were obtained after analysis of both cohorts separately. Discrepancy analysis by viral load assessment for the most common discordant hrHPV types (HPV16, -18, and -52) showed that samples which were SPF(10) positive only for these types had viral loads significantly lower than those for samples that were positive by both assays (analysis of variance; P < or = 0.006). Our data indicate that GP5+/6+-PCR has a better clinical performance than SPF(10) for women who are diagnosed with CIN 3 after prior normal cytology results. The extra positivity scored by SPF(10) mainly involved infections characterized by low viral loads that do not result in CIN 3.
authors.affiliation: Department of Pathology, VU University Medical Center, de Boelelaan 1117, 1081 HV Amsterdam, The Netherlands.
authors.forename: A T
authors.initials: AT
authors.lastname: Hesselink
authors.forename: M A P C
authors.initials: MA
authors.lastname: van Ham
authors.forename: D A M
authors.initials: DA
authors.lastname: Heideman
authors.forename: Z M A
authors.initials: ZM
authors.lastname: Groothuismink
authors.forename: L
authors.initials: L
authors.lastname: Rozendaal
authors.forename: J
authors.initials: J
authors.lastname: Berkhof
authors.forename: F J
authors.initials: FJ
authors.lastname: van Kemenade
authors.forename: L A F G
authors.initials: LA
authors.lastname: Massuger
authors.forename: W J G
authors.initials: WJ
authors.lastname: Melchers
authors.forename: C J L M
authors.initials: CJ
authors.lastname: Meijer
authors.forename: P J F
authors.initials: PJ
authors.lastname: Snijders
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008875:Middle Aged; D009693:Nucleic Acid Hybridization / Q000379:methods*; D027383:Papillomaviridae / Q000235:genetics / Q000302:isolation & purification*; D030361:Papillomavirus Infections / Q000175:diagnosis* / Q000821:virology; D016133:Polymerase Chain Reaction / Q000379:methods*; D011237:Predictive Value of Tests; D012680:Sensitivity and Specificity; D014599:Uterus / Q000821:virology*; D014764:Viral Proteins / Q000235:genetics; D002578:Uterine Cervical Dysplasia / Q000821:virology*
chemical_list: D014764:Viral Proteins