Effect of cervical cytologic status on the association between human papillomavirus type 16 DNA load and the risk of cervical intraepithelial neoplasia grade 3.
BACKGROUND
Although correlations between cervical cytologic status and both human papillomavirus (HPV) load and histopathologic status are recognized, it is largely undetermined whether the association between the HPV DNA load and the risk of cervical intraepithelial neoplasia grade 3 (CIN-3) differs on the basis of cervical cytologic findings.


METHODS
Study subjects were 821 women enrolled in the ASCUS-LSIL Triage Study who tested positive for HPV-16 at entry. Women were followed semiannually for 2 years. The baseline HPV-16 load was measured by real-time polymerase chain reaction.


RESULTS
CIN-3 was confirmed in 286 (34.8%) of 821 women during the 2-year follow-up period. The adjusted odds ratio (OR) of the 2-year cumulative risk of CIN-3 was 1.46 (95% confidence interval [CI], 1.29-1.64) per 1 log(10) increase in virus load. The ORs varied from 1.66 (95% CI, 1.16-2.37) for women with normal cytologic findings at enrollment to 0.86 (95% CI, 0.61-1.20) for those with high-grade squamous intraepithelial lesions. Among women with normal cytologic findings at enrollment, the area under the receiver operating characteristic curve for detection of CIN-3 on the basis of the virus load was 0.70 (95% CI, 0.61-0.78).


CONCLUSIONS
The HPV-16 DNA load was associated with the risk of developing CIN-3, but the associations varied with cytologic findings at the time of virus load measurement. The clinical usefulness of measuring the HPV-16 load as a means to detect CIN-3 was minimal, even in women with normal cytologic findings.
Xi
Long Fu
LF
Department of Pathology, School of Medicine, University of Washington, Seattle, Washington 98103, USA. longfu@u.washington.edu
Kiviat
Nancy B
NB
Galloway
Denise A
DA
Zhou
Xiao-Hua
XH
Ho
Jesse
J
Koutsky
Laura A
LA
D000293:Adolescent; D000328:Adult; D002584:Cervix Uteri / Q000166:cytology / Q000473:pathology* / Q000821:virology; D004279:DNA, Viral / Q000032:analysis* / Q000235:genetics; D005260:Female; D052162:Human papillomavirus 16 / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D008137:Longitudinal Studies; D030361:Papillomavirus Infections / Q000473:pathology* / Q000821:virology*; D016133:Polymerase Chain Reaction / Q000379:methods; D012372:ROC Curve; D013223:Statistics as Topic; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis / Q000473:pathology* / Q000821:virology*
D004279:DNA, Viral