Human papillomavirus type 18 DNA load and 2-year cumulative diagnoses of cervical intraepithelial neoplasia grades 2-3

Long Fu Xi, Laura A. Koutsky, Philip E. Castle, Cosette M. Wheeler, Denise A. Galloway, Constance Mao, Jesse Ho, Nancy B. Kiviat

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)153-161
Number of pages9
JournalJournal of the National Cancer Institute
Volume101
Issue number3
DOIs
StatePublished - Feb 2009
Externally publishedYes

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Human papillomavirus 18
Cervical Intraepithelial Neoplasia
DNA
Confidence Intervals
Cell Biology
Linear Models
Triage
Squamous Intraepithelial Lesions of the Cervix
Coinfection

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Human papillomavirus type 18 DNA load and 2-year cumulative diagnoses of cervical intraepithelial neoplasia grades 2-3. / Xi, Long Fu; Koutsky, Laura A.; Castle, Philip E.; Wheeler, Cosette M.; Galloway, Denise A.; Mao, Constance; Ho, Jesse; Kiviat, Nancy B.

In: Journal of the National Cancer Institute, Vol. 101, No. 3, 02.2009, p. 153-161.

Research output: Contribution to journalArticle

Xi, Long Fu ; Koutsky, Laura A. ; Castle, Philip E. ; Wheeler, Cosette M. ; Galloway, Denise A. ; Mao, Constance ; Ho, Jesse ; Kiviat, Nancy B. / Human papillomavirus type 18 DNA load and 2-year cumulative diagnoses of cervical intraepithelial neoplasia grades 2-3. In: Journal of the National Cancer Institute. 2009 ; Vol. 101, No. 3. pp. 153-161.
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title = "Human papillomavirus type 18 DNA load and 2-year cumulative diagnoses of cervical intraepithelial neoplasia grades 2-3",
abstract = "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.",
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T1 - Human papillomavirus type 18 DNA load and 2-year cumulative diagnoses of cervical intraepithelial neoplasia grades 2-3

AU - Xi, Long Fu

AU - Koutsky, Laura A.

AU - Castle, Philip E.

AU - Wheeler, Cosette M.

AU - Galloway, Denise A.

AU - Mao, Constance

AU - Ho, Jesse

AU - Kiviat, Nancy B.

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N2 - 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.

AB - 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.

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