Risk for high-grade cervical intraepithelial neoplasia associated with variants of human papillomavirus types 16 and 18.
BACKGROUND
Although the variant lineages of human papillomavirus (HPV) types 16 and 18 are well established, their individual associations with high-grade cervical intraepithelial neoplasia (CIN) have not been extensively evaluated.


METHODS
Study subjects were women participating in the Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous Intraepithelial Lesion Triage Study who were positive for HPV16 or HPV18 at enrollment. These women were followed every 6 months for 2 years. Viral isolates from enrollment samples were characterized by DNA sequencing and classified as variant lineages.


RESULTS
Over a 2-year study period, CIN3 was histologically diagnosed in 291 of the 779 HPV16-positive women and 47 of the 275 HPV18-positive women. Among women without CIN2-3 at enrollment, the risk of subsequent CIN3 was 2.7-fold greater for those with HPV16 African-2 [95% confidence interval (95% CI), 1.0-7.0] and 3.1-fold greater for those with HPV16 Asian American (95% CI, 1.6-6.0), compared with European variants. Relative to infection with HPV18 African variants, the risk associating subsequent CIN3 was 3.8 (95% CI, 0.9-17.2) for infection with HPV18 European variants and 4.8 (95% CI, 1.0-23.6) for infection with HPV18 Asian American variants. Similar associations were observed when the 2-year prevalence of CIN3 was used as the end point. Further, for those with HPV16 European variants, the 2-year prevalence of CIN3 was higher in White women than in African American women (P = 0.01); this trend was reversed for those with HPV16 African-1 variants (P = 0.22). A similar pattern was present for infections with HPV18 European versus African variants.


CONCLUSIONS
The lineages of HPV16 and HPV18 variants are associated with differing risks for high-grade CIN.
Xi
Long Fu
LF
Department of Pathology, School of Medicine, University of Washington, Seattle, Washington 98103, USA. longfu@u.washington.edu
Koutsky
Laura A
LA
Hildesheim
Allan
A
Galloway
Denise A
DA
Wheeler
Cosette M
CM
Winer
Rachel L
RL
Ho
Jesse
J
Kiviat
Nancy B
NB
D000293:Adolescent; D000328:Adult; D005260:Female; D014644:Genetic Variation; D052162:Human papillomavirus 16 / Q000302:isolation & purification*; D052161:Human papillomavirus 18 / Q000302:isolation & purification*; D006801:Humans; D030361:Papillomavirus Infections / Q000453:epidemiology / Q000821:virology*; D012307:Risk Factors; D014481:United States / Q000453:epidemiology; D002583:Uterine Cervical Neoplasms / Q000453:epidemiology / Q000821:virology*; D014626:Vaginal Smears; D002578:Uterine Cervical Dysplasia / Q000453:epidemiology / Q000821:virology*