title: Comparison of methods using paraffin-embedded tissues and exfoliated cervical cells to evaluate human papillomavirus genotype attribution.
abstract: Monitoring the attribution of human papillomavirus (HPV) genotypes to cervical precancerous lesions is essential in assessing the efficacy of HPV vaccines. To resolve the lack of studies comparing the HPV genotyping procedures used to estimate HPV genotype attribution, we undertook a retrospective cross-sectional study to determine the appropriate genotyping procedures for evaluating the potential efficacy of HPV vaccines. Three procedures, including two different genotyping methods, Clinichip HPV test (C-Chip) and modified GP5+/6+ PCR coupled to fluorescent bead sorter detection (MGP), using exfoliated cervical cells (C-Chip and C-MGP, respectively) or formalin-fixed paraffin-embedded tissues (F-MGP), were compared. The overall agreement in detecting high-risk HPV was 88.5-92.1% among the three procedures, and genotype-specific agreement was 83.9-100% for all pairwise comparisons. In cervical intraepithelial neoplasia grade 2/3 specimens, HPV16/18 attribution estimated with the hierarchical attribution method was consistent among the procedures: 52.3% (45/86) for C-Chip, 54.7% (47/86) for C-MGP, and 52.3% (45/86) for F-MGP (P = 0.81). HPV16/18/31/33/45/52/58 hierarchical attribution was 88.4% (76/86) with C-Chip, 86.0% (74/86) with C-MGP, and 83.7% (72/86) with F-MGP (P = 0.49). In cervical intraepithelial neoplasia grade 3 specimens, the corresponding hierarchical attribution was 96.4% (53/55) with C-Chip, 89.1% (49/55) with C-MGP, and 94.5% (52/55) with F-MGP (P = 0.27). Although F-MGP is theoretically a reliable method for determining HPV genotype attribution, it is acceptable to use C-Chip or C-MGP, coupled to the hierarchical attribution formula to correct the bias of multiple infections. These approaches using exfoliated cervical cells are practical for monitoring the efficacy of HPV vaccines.
authors: Department of Obstetrics and Gynecology, School of Medicine, Fujita Health University, Toyoake, Japan.
authors: Yutaka
authors: Y
authors: Torii
authors: Department of Obstetrics and Gynecology, School of Medicine, Fujita Health University, Toyoake, Japan. fujiit44@fujita-hu.ac.jp.|Department of Obstetrics and Gynecology, School of Medicine, Keio University, Tokyo, Japan. fujiit44@fujita-hu.ac.jp.
authors: Takuma
authors: T
authors: Fujii
authors: Pathogen Genomics Center, National Institute of Infectious Diseases, Tokyo, Japan.
authors: Iwao
authors: I
authors: Kukimoto
authors: Department of Obstetrics and Gynecology, School of Medicine, Keio University, Tokyo, Japan.
authors: Miyuki
authors: M
authors: Saito
authors: Department of Obstetrics and Gynecology, School of Medicine, Keio University, Tokyo, Japan.
authors: Takashi
authors: T
authors: Iwata
authors: Division of Medical Statistics, School of Medicine, Fujita Health University, Toyoake, Japan.
authors: Hiroshi
authors: H
authors: Takahashi
authors: Department of Obstetrics and Gynecology, School of Medicine, Fujita Health University, Toyoake, Japan.
authors: Ryoko
authors: R
authors: Ichikawa
authors: Department of Obstetrics and Gynecology, School of Medicine, Fujita Health University, Toyoake, Japan.
authors: Satoshi
authors: S
authors: Kawai
authors: Department of Obstetrics and Gynecology, School of Medicine, Fujita Health University, Toyoake, Japan.
authors: Sayaka
authors: S
authors: Otani
authors: Department of Obstetrics and Gynecology, School of Medicine, Keio University, Tokyo, Japan.
authors: Daisuke
authors: D
authors: Aoki
mesh_terms: D000328:Adult; D002584:Cervix Uteri / Q000473:pathology* / Q000821:virology*; D003430:Cross-Sectional Studies; D004279:DNA, Viral; D005260:Female; D005838:Genotype; D060005:Genotyping Techniques; D006801:Humans; D008875:Middle Aged; D060787:Neoplasm Grading; D027383:Papillomaviridae / Q000235:genetics*; D030361:Papillomavirus Infections / Q000150:complications / Q000453:epidemiology* / Q000517:prevention & control / Q000821:virology*; D053918:Papillomavirus Vaccines / Q000276:immunology; D055815:Young Adult; D002578:Uterine Cervical Dysplasia / Q000453:epidemiology / Q000209:etiology / Q000473:pathology
chemical_list: D004279:DNA, Viral; D053918:Papillomavirus Vaccines
keywords: Cervical intraepithelial neoplasia; HPV vaccine; exfoliated cervical cell; formalin-fixed paraffin-embedded tissue; human papillomavirus