title: Viral load as a predictor of the risk of cervical intraepithelial neoplasia.
abstract: HPV infections are believed to be a necessary cause of cervical cancer. Viral burden, as a surrogate indicator for persistence, may help predict risk of subsequent SIL. We used results of HPV test and cytology data repeated every 4-6 months in 2,081 women participating in a longitudinal study of the natural history of HPV infection and cervical neoplasia in São Paulo, Brazil. Using the MY09/11 PCR protocol, 473 women were positive for HPV DNA during the first 2 visits. We retested all positive specimens by a quantitative, low-stringency PCR method to measure viral burden in cervical cells. Mean viral loads and 95% CIs were calculated using log-transformed data. RRs and 95% CIs of incident SIL were calculated by proportional hazards models, adjusting for age and HPV oncogenicity. The risk of incident lesions increased with viral load at enrollment. The mean number of viral copies/cell at enrollment was 2.6 for women with no incident lesions and increased (trend p = 0.003) to 15.1 for women developing 3 or more SIL events over 6 years of follow-up. Compared to those with <1 copy per cell in specimens tested during the first 2 visits, RRs for incident SIL increased from 1.9 (95% CI 0.8-4.2) for those with 1-10 copies/cell to 4.5 (95% CI 1.9-10.7) for those with >1,000 copies/cell. The equivalent RR of HSIL for >1,000 copies/cell was 2.6 (95% CI 0.5-13.2). Viral burden appears to have an independent effect on SIL incidence. Measurement of viral load, as a surrogate for HPV persistence, may identify women at risk of developing cervical cancer precursors.
authors.affiliation: Division of Cancer Epidemiology, McGill University, 546 Pine Avenue West, Montreal, Quebec, Canada H2W 1S6.
authors.forename: Nicolas F
authors.initials: NF
authors.lastname: Schlecht
authors.forename: Andrea
authors.initials: A
authors.lastname: Trevisan
authors.forename: Eliane
authors.initials: E
authors.lastname: Duarte-Franco
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Rohan
authors.forename: Alex
authors.initials: A
authors.lastname: Ferenczy
authors.forename: Luisa L
authors.initials: LL
authors.lastname: Villa
authors.forename: Eduardo L
authors.initials: EL
authors.lastname: Franco
mesh_terms: D000293:Adolescent; D000328:Adult; D001938:Brazil; D002584:Cervix Uteri / Q000166:cytology; D015331:Cohort Studies; D004279:DNA, Viral / Q000378:metabolism; D005260:Female; D006801:Humans; D008875:Middle Aged; D027383:Papillomaviridae / Q000378:metabolism*; D030361:Papillomavirus Infections / Q000150:complications*; D012307:Risk Factors; D013997:Time Factors; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000821:virology*; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis* / Q000821:virology*
chemical_list: D004279:DNA, Viral