title: Type-dependent association between risk of cervical intraepithelial neoplasia and viral load of oncogenic human papillomavirus types other than types 16 and 18.
abstract: Studies of the clinical relevance of human papillomavirus (HPV) DNA load have focused mainly on HPV16 and HPV18. Data on other oncogenic types are rare. Study subjects were women enrolled in the atypical squamous cells of undetermined significance (ASC-US) and low-grade squamous intraepithelial lesion (LSIL) triage study who had ≥1 of 11 non-HPV16/18 oncogenic types detected during a 2-year follow-up at 6-month intervals. Viral load measurements were performed on the first type-specific HPV-positive specimens. The association of cervical intraepithelial neoplasia grades 2-3 (CIN2/3) with type-specific HPV DNA load was assessed with discrete-time Cox regression. Overall, the increase in the cumulative risk of CIN2/3 per 1 unit increase in log10-transformed viral load was statistically significant for four types within species 9 including HPV31 (adjusted hazard ratio [HRadjusted] = 1.32: 95% confidence interval [CI], 1.14-1.52), HPV35 (HRadjusted= 1.47; 95% CI, 1.23-1.76), HPV52 (HRadjusted= 1.14; 95% CI, 1.01-1.30) and HPV58 (HRadjusted= 1.49; 95% CI, 1.23-1.82). The association was marginally significant for HPV33 (species 9) and HPV45 (species 7) and was not appreciable for other types. The per 1 log10-unit increase in viral load of a group of species 9 non-HPV16 oncogenic types was statistically significantly associated with risk of CIN2/3 for women with a cytologic diagnosis of within normal limits, ASC-US, or LSIL at the first HPV-positive visit but not for those with high-grade SIL. Findings suggest that the viral load-associated risk of CIN2/3 is type-dependent, and mainly restricted to the species of HPV types related to HPV16, which shares this association.
authors.affiliation: Department of Pathology, School of Medicine, University of Washington, Seattle, WA.|Department of Epidemiology, University of Washington, Seattle, WA.
authors.forename: Long
authors.initials: L
authors.lastname: Fu Xi
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD.
authors.forename: Mark
authors.initials: M
authors.lastname: Schiffman
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research, Peking University School of Oncology, Beijing, People's Republic of China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Ke
authors.affiliation: Department of Biostatistics, School of Public Health and Community Medicine, University of Washington, Seattle, WA.
authors.forename: James P
authors.initials: JP
authors.lastname: Hughes
authors.affiliation: Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA.
authors.forename: Denise A
authors.initials: DA
authors.lastname: Galloway
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research, Peking University School of Oncology, Beijing, People's Republic of China.
authors.forename: Zhonghu
authors.initials: Z
authors.lastname: He
authors.affiliation: Department of Pathology, School of Medicine, University of Washington, Seattle, WA.
authors.forename: Ayaka
authors.initials: A
authors.lastname: Hulbert
authors.affiliation: Department of Epidemiology, University of Washington, Seattle, WA.
authors.forename: Rachel L
authors.initials: RL
authors.lastname: Winer
authors.affiliation: Department of Epidemiology, University of Washington, Seattle, WA.
authors.forename: Laura A
authors.initials: LA
authors.lastname: Koutsky
authors.affiliation: Department of Pathology, School of Medicine, University of Washington, Seattle, WA.
authors.forename: Nancy B
authors.initials: NB
authors.lastname: Kiviat
mesh_terms: D004279:DNA, Viral / Q000235:genetics* / Q000302:isolation & purification; D055088:Early Detection of Cancer; D005260:Female; D005838:Genotype; D052162:Human papillomavirus 16 / Q000472:pathogenicity; D052161:Human papillomavirus 18 / Q000472:pathogenicity; D058952:Human papillomavirus 31 / Q000235:genetics / Q000472:pathogenicity; D006801:Humans; D027383:Papillomaviridae / Q000145:classification / Q000235:genetics / Q000472:pathogenicity*; D030361:Papillomavirus Infections / Q000453:epidemiology / Q000821:virology*; D014626:Vaginal Smears; D019562:Viral Load; D002578:Uterine Cervical Dysplasia / Q000453:epidemiology / Q000821:virology*
chemical_list: D004279:DNA, Viral
keywords: cervical intraepithelial neoplasia; human papillomavirus; risk association; viral load