Journal of the National Cancer Institute Advance Access originally published online on January 27, 2009
JNCI Journal of the National Cancer Institute 2009 101(3):153-161; doi:10.1093/jnci/djn461
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© The Author 2009. Published by Oxford University Press.
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Human Papillomavirus Type 18 DNA Load and 2-Year Cumulative Diagnoses of Cervical Intraepithelial Neoplasia Grades 2–3
Affiliations of authors: Department of Pathology (LFX, JH, NBK) and Department of Obstetrics and Gynecology (CM), School of Medicine, Department of Epidemiology (LFX, LAK), School of Public Health and Community Medicine, University of Washington, Seattle, WA; Division of Cancer Epidemiology and Genetics (PEC), National Cancer Institute, National Institutes of Health, Bethesda, MD; Department of Microbiology and Department of Molecular Genetics, School of Medicine, University of New Mexico, Albuquerque, NM (CMW); Fred Hutchinson Cancer Research Center, Seattle, WA (DAG)
Correspondence to: Long Fu Xi, MD, PhD, Department of Pathology, School of Medicine, University of Washington, 1914 North 34th St, Suite 300, Seattle, WA 98103 (e-mail: longfu{at}u.washington.edu).
Background: The clinical relevance of the amount of human papillomavirus type 18 (HPV18) DNA in cervical tissue (ie, HPV18 DNA load) is unknown.
Methods: Study subjects were 303 women who were HPV18 positive at enrollment into the Atypical Squamous Cells of Undetermined Significance (ASC-US) and Low-Grade Squamous Intraepithelial Lesion (LSIL) Triage Study. HPV18 DNA load, expressed as copies of HPV18 per nanogram of cellular DNA, at enrollment was quantitatively measured. Subjects were followed up semiannually for a period of 2 years for detection of cervical intraepithelial neoplasia 2–3 (CIN2–3). A linear regression model was used to examine associations of CIN2–3 with HPV18 DNA load. All statistical tests were two-sided.
Results: CIN2–3 was confirmed in 92 of 303 (30.4%) HPV18-positive women. Among women without CIN2–3, HPV18 DNA load was positively associated with increasing severity of cervical cytology at enrollment (Ptrend < .001). However, among those with CIN2–3, HPV18 DNA load was not associated with severity of cervical cytology at enrollment (Ptrend = .33). The ratios of geometric means of HPV18 DNA load at enrollment among women with CIN2–3, relative to those without, were 6.06 (95% confidence interval [CI] = 0.31 to 117.92) for those with normal cytology at enrollment, 0.50 (95% CI = 0.10 to 2.44) for those with ASC-US, 0.11 (95% CI = 0.03 to 0.46) for those with LSIL, and 0.07 (95% CI = 0.01 to 0.80) for those with high-grade squamous intraepithelial lesion (HSIL). After adjusting for age and coinfection with other high-risk HPVs, a statistically significant association of lower HPV18 DNA load with CIN2–3 was observed among women with LSIL or HSIL at enrollment (P = .02). Within the 2-year period, HPV18 DNA load was unrelated to the timing of CIN2–3 diagnosis. Overall results were similar when the outcome was CIN3.
Conclusions: HPV18 DNA load was higher for women with LSIL or HSIL at enrollment with no evidence of CIN2–3 during the 2-year follow-up period than it was for women with CIN2–3. Thus, testing for high levels of HPV18 DNA does not appear to be clinically useful.
| CONTEXT AND CAVEATS Prior knowledge Human papillomavirus type 18 (HPV18) is often detected in invasive cervical cancer, but it is unknown whether high amounts of HPV18 DNA in cervical tissue are associated with cervical intraepithelial neoplasia (CIN) grades 2–3, the precursor of cervical cancer. Study design Women (n = 303) who were HPV18 positive at enrollment in the Atypical Squamous Cells of Undetermined Significance and Low-Grade Squamous Intraepithelial Lesion Triage Study were monitored semiannually for 2 years. Contributions CIN2–3 was diagnosed in 92 women. The amount of HPV18 DNA was positively associated with severity of cervical cytology at enrollment among women without CIN2-3 during the 2-year study period, and among those with low- or high-grade sequamous intraepithelial lesions at enrollment, it was lower in women with CIN2-3 than those without CIN2-3. Implications Testing for high amounts of HPV18 DNA in cervical tissue samples may not be clinically useful. Limitations The study sample size is small. Lesions would have likely been detected earlier in the study than in the general population. HPV18 DNA levels may fluctuate during the course of infection. From the Editors
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Manuscript received May 26, 2008; revised October 30, 2008; accepted November 14, 2008.
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J Natl Cancer Inst 2009 101: 127.
J Natl Cancer Inst 2009 101: 127.
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  L. F. Xi, Z. R. Edelstein, C. Meyers, J. Ho, S. L. Cherne, and M. Schiffman Human Papillomavirus Types 16 and 18 DNA Load in Relation to Coexistence of Other Types, Particularly Those in the Same Species Cancer Epidemiol. Biomarkers Prev., September 1, 2009; 18(9): 2507 - 2512. [Abstract] [Full Text] [PDF]
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