title: Attributing oncogenic human papillomavirus genotypes to high-grade cervical neoplasia: which type causes the lesion?
abstract: Human papillomavirus (HPV) is found in most women with high-grade cervical intraepithelial neoplasia (CIN) 2/3 in cervical cytology and biopsies. Multiple high-risk HPV (hrHPV) genotypes are present in 15% to 50% of cytology samples. We have shown by laser-capture microscopy (LCM)-polymerase chain reaction (PCR) that each lesion is associated with a single hrHPV type. Attribution of hrHPV types to CIN2/3 is important to understand the oncogenic role of different types and the limitations of cytologic typing. We studied hrHPV genotypes in 257 women with histologic CIN2/3 referred on the basis of abnormal cytology. HPV typing was done on cytology and CIN2/3 biopsies. If the whole-tissue section of the biopsy was positive for multiple hrHPV types, LCM-PCR was performed. We found 181 (70%) single and 71 (28%) multiple hrHPV infections in cytology, with 5 (2%) cases HPV-positive only on whole-tissue section PCR. Of cases with multiple cytologic hrHPV infections, 47/71 (66%) showed a single type in CIN2/3 lesions. In total, in 232 of 257 (90%) women with CIN2/3, a single hrHPV type caused CIN2/3. One was nonattributable on the LCM level. The remaining 24 women had 2 or more contiguous or separated lesions, each associated with a single hrHPV infection. The probability of HPV16 being present in CIN2/3, if detected in cytology, was 0.96 (95% confidence interval=0.90-0.98). LCM-PCR confirms that only 9% of histologic CIN2/3 is associated with multiple hrHPV types, much less than cytology would indicate, and each lesion was associated with a single hrHPV infection.
authors.affiliation: *DDL Diagnostic Laboratory, Rijswijk †Department of Epidemiology and Biostatistics, VU Medical Center, Amsterdam, The Netherlands ‡Department of Pathology, CRESIB (Centre de Recerca en Salut Internacional de Barcelona) §Institut Clinic of Gynecology, Obstetrics and Neonatology, Hospital Clínic, Spain ∥Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD.
authors.forename: Jacolien
authors.initials: J
authors.lastname: van der Marel
authors.forename: Johannes
authors.initials: J
authors.lastname: Berkhof
authors.forename: Jaume
authors.initials: J
authors.lastname: Ordi
authors.forename: Aureli
authors.initials: A
authors.lastname: Torné
authors.forename: Marta
authors.initials: M
authors.lastname: Del Pino
authors.forename: Romy
authors.initials: R
authors.lastname: van Baars
authors.forename: Mark
authors.initials: M
authors.lastname: Schiffman
authors.forename: Nicolas
authors.initials: N
authors.lastname: Wentzensen
authors.forename: David
authors.initials: D
authors.lastname: Jenkins
authors.forename: Wim G V
authors.initials: WG
authors.lastname: Quint
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D003127:Colposcopy; D004279:DNA, Viral / Q000235:genetics*; D005260:Female; D005838:Genotype; D061809:Human Papillomavirus DNA Tests; D006801:Humans; D061346:Laser Capture Microdissection; D008875:Middle Aged; D060787:Neoplasm Grading; D009426:Netherlands; D027383:Papillomaviridae / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification / Q000472:pathogenicity; D030361:Papillomavirus Infections / Q000150:complications / Q000175:diagnosis / Q000821:virology*; D011237:Predictive Value of Tests; D012307:Risk Factors; D013030:Spain; D002583:Uterine Cervical Neoplasms / Q000473:pathology / Q000821:virology*; D055815:Young Adult; D002578:Uterine Cervical Dysplasia / Q000473:pathology / Q000821:virology*
chemical_list: D004279:DNA, Viral