title: High load for most high risk human papillomavirus genotypes is associated with prevalent cervical cancer precursors but only HPV16 load predicts the development of incident disease.
abstract: Cervicovaginal human papillomavirus (HPV) viral load has been purported as a potential marker for the detection of high-grade cervical intraepithelial neoplasia or cancer (>/=CIN2). To examine disease association with type-specific viral load for the full-range of anogenital HPV infections, we conducted cross-sectional and prospective analyses of approximately 2,000 HPV-infected women from a 10,000-woman population-based study in Guanacaste, Costa Rica with 7 years of follow-up. Cervical specimens were tested for >40 HPV types using a MY09/MY11 L1 consensus primer PCR method with type-specific dot blot hybridization and PCR signal intensity as a measure of viral load. A positive association was observed between prevalent >/=CIN2 and high viral load compared to low viral load for women with baseline single HPV16 infections (OR = 19.2, 95% CI = 4.4-83.2) and single non-16 carcinogenic infections (OR = 9.2, 95% CI = 2.1-39.9). Inclusion of women with multiple HPV types did not substantially change these associations. In prospective follow-up, only women infected with HPV16 alone (OR = 27.2, 95% = 3.5-213.5) had a strong association between high viral load and incident >/=CIN2; non-16 carcinogenic high viral load was not associated with incident >/=CIN2 (OR = 0.7, 95% CI = 0.2-1.9). Single noncarcinogenic type viral load was not associated with increased risk of prevalent or incident >/=CIN2 (OR = 1.2 and 1.1, respectively). In conclusion, carcinogenic high viral load was associated with prevalent >/=CIN2; however HPV16 was uniquely associated with incident >/=CIN2. The extent to which these observations can be translated into clinical practice must be rigorously examined in the context of the method of viral load measurement and the type-specific differences observed for incident >/=CIN2.
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. pgravitt@jhsph.edu
authors.forename: Patti E
authors.initials: PE
authors.lastname: Gravitt
authors.forename: Melinda Butsch
authors.initials: MB
authors.lastname: Kovacic
authors.forename: Rolando
authors.initials: R
authors.lastname: Herrero
authors.forename: Mark
authors.initials: M
authors.lastname: Schiffman
authors.forename: Concepcion
authors.initials: C
authors.lastname: Bratti
authors.forename: Allan
authors.initials: A
authors.lastname: Hildesheim
authors.forename: Jorge
authors.initials: J
authors.lastname: Morales
authors.forename: Mario
authors.initials: M
authors.lastname: Alfaro
authors.forename: Mark E
authors.initials: ME
authors.lastname: Sherman
authors.forename: Sholom
authors.initials: S
authors.lastname: Wacholder
authors.forename: Ana-Cecilia
authors.initials: AC
authors.lastname: Rodriguez
authors.forename: Robert D
authors.initials: RD
authors.lastname: Burk
mesh_terms: D000328:Adult; D000368:Aged; D003364:Costa Rica / Q000453:epidemiology; D003430:Cross-Sectional Studies; D004279:DNA, Viral / Q000302:isolation & purification; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D052162:Human papillomavirus 16 / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D015994:Incidence; D008403:Mass Screening; D008875:Middle Aged; D016017:Odds Ratio; D027383:Papillomaviridae / Q000302:isolation & purification; D030361:Papillomavirus Infections / Q000150:complications* / Q000453:epidemiology; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D015995:Prevalence; D011446:Prospective Studies; D014412:Tumor Virus Infections / Q000150:complications* / Q000453:epidemiology; D002583:Uterine Cervical Neoplasms / Q000453:epidemiology* / Q000821:virology*; D019562:Viral Load; D002578:Uterine Cervical Dysplasia / Q000453:epidemiology / Q000821:virology
chemical_list: D004279:DNA, Viral