title: Long-term risk of cervical intraepithelial neoplasia grade 3 or worse according to high-risk human papillomavirus genotype and semi-quantitative viral load among 33,288 women with normal cervical cytology.
abstract: In this prospective cohort study, we estimated the long-term risk of cervical intraepithelial neoplasia grade 3 or cancer (CIN3+) by high-risk human papillomavirus (hrHPV) genotype and semi-quantitative viral load at baseline among 33,288 women aged 14-90 years with normal baseline cytology. During 2002-2005, residual liquid-based cervical cytology samples were collected from women screened for cervical cancer in Copenhagen, Denmark. Samples were HPV-tested with Hybrid Capture 2 (HC2) and genotyped with INNO-LiPA. Semi-quantitative viral load was measured by HC2 relative light units in women with single hrHPV infections. The cohort was followed in a nationwide pathology register for up to 11.5 years. In women aged ≥30 years at baseline, the 8-year absolute risk for CIN3+ following baseline detection of HPV16 was 21.8% (95% confidence interval [CI]: 18.0-25.6%). The corresponding risks for HPV18, HPV31, HPV33, and other hrHPV types, respectively, were 12.8% (95% CI: 7.6-18.0%), 11.3% (95% CI: 7.7-14.9%), 12.9% (95% CI: 7.0-18.8%) and 3.9% (95% CI: 2.7-5.2%). Similar absolute risk estimates were observed in women aged <30 years. Higher HPV16-viral load was associated with increased risk of CIN3+ (hazard ratio = 1.34, 95% CI: 1.10-1.64, per 10-fold increase in viral load). A similar trend, although statistically nonsignificant, was found for viral load of HPV18. The 8-year absolute risk of CIN3+ in women with HPV16-viral load ≥100.0 pg/ml was 30.2% (95% CI: 21.9-38.6%). Our results support that hrHPV genotyping during cervical cancer screening may help identify women at highest risk of CIN3+.
authors.affiliation: Unit of Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Copenhagen, Denmark.
authors.forename: Louise T
authors.initials: LT
authors.lastname: Thomsen
authors.forename: Kirsten
authors.initials: K
authors.lastname: Frederiksen
authors.forename: Christian
authors.initials: C
authors.lastname: Munk
authors.forename: Jette
authors.initials: J
authors.lastname: Junge
authors.forename: Thomas
authors.initials: T
authors.lastname: Iftner
authors.forename: Susanne K
authors.initials: SK
authors.lastname: Kjaer
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D052685:Alphapapillomavirus / Q000145:classification / Q000235:genetics* / Q000502:physiology; D004279:DNA, Viral / Q000235:genetics; D003718:Denmark; D055088:Early Detection of Cancer; D005260:Female; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D030361:Papillomavirus Infections / Q000175:diagnosis* / Q000821:virology; D011446:Prospective Studies; D012307:Risk Factors; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis / Q000821:virology*; D014626:Vaginal Smears; D019562:Viral Load; D055815:Young Adult; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis / Q000821:virology*
chemical_list: D004279:DNA, Viral
keywords: HPV genotypes; HPV viral load; cervical cancer; high-grade cervical intraepithelial neoplasia; long-term risk