Persistence of an incident human papillomavirus infection and timing of cervical lesions in previously unexposed young women.
BACKGROUND
We analyzed data from a cohort of 553 women enrolled in the placebo arm of a randomized controlled trial of the human papillomavirus (HPV) 16/18 vaccine to study the timing of the occurrence of squamous intraepithelial lesions (SIL) or cervical intraepithelial neoplasia (CIN) following incident HPV infection and its relation to persistence of the infection.


METHODS
At entry, women were cytologically negative, HPV 16/18 seronegative, and high-risk HPV (HR-HPV) DNA negative. Cervicovaginal samples were initially collected at 3-month and cervical samples at 6-month intervals. We estimated the mean time to SIL/CIN, relative risks of SIL/CIN following incident HPV, and odds ratios between persistent HPV and SIL/CIN.


RESULTS
The mean time for SIL/CIN detection was 43.3 [95% confidence interval (95% CI), 36.4-50.1] and 46.4 (95% CI, 42.0-50.7) months from first infection with HPV 16/18 and other HR-HPVs, respectively. Relative risks of SIL/CIN following incident HPV infection were 66.2 (95% CI, 14.9-295.1) for HPV 16/18 and 50.9 (95% CI, 11.5-225.4) for other HR-HPVs. The odds ratios of SIL/CIN for persistent HPV 16/18 infection, defined as a minimum of two and three (6 monthly) visits, were, respectively, 169.0 (95% CI, 37.2-768.6) and 169.1 (95% CI, 31.5-907.4). The majority of women with cervical infection with HPV 16/18 lasting >6 months (33 of 51, 65%) developed SIL and/or CIN.


CONCLUSIONS
These analyses provide the first actuarial estimate of mean time between incident HR-HPV infection in previously uninfected women and onset of cervical lesion development. Persistent HR-HPV infection, particularly HPV 16/18, is a strong predictor of cervical lesion risk and potentially a reliable end point for clinical HPV research.
Trottier
Helen
H
Division of Cancer Epidemiology, McGill University, 546 Pine Avenue West, Montreal, Quebec, Canada H2W1S6. eduardo.franco@mcgill.ca.
Mahmud
Salaheddin M
SM
Lindsay
Lisa
L
Jenkins
David
D
Quint
Wim
W
Wieting
Susan L
SL
Schuind
Anne
A
Franco
Eduardo L
EL
D000293:Adolescent; D002584:Cervix Uteri / Q000473:pathology / Q000821:virology*; D004279:DNA, Viral / Q000032:analysis; D004311:Double-Blind Method; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D015994:Incidence; D030361:Papillomavirus Infections / Q000453:epidemiology / Q000517:prevention & control*; D053918:Papillomavirus Vaccines / Q000008:administration & dosage; D016016:Proportional Hazards Models; D013997:Time Factors; D014412:Tumor Virus Infections / Q000453:epidemiology / Q000517:prevention & control*; D055815:Young Adult; D002578:Uterine Cervical Dysplasia / Q000453:epidemiology / Q000821:virology*
D004279:DNA, Viral; D053918:Papillomavirus Vaccines