A prospective study of high-grade cervical neoplasia risk among human papillomavirus-infected women

Philip E. Castle, Sholom Wacholder, Attila T. Lorincz, David R. Scott, Mark E. Sherman, Andrew G. Glass, Brenda B. Rush, John E. Schussler, Mark Schiffman

Research output: Contribution to journalArticle

177 Citations (Scopus)

Abstract

Background: In case-control studies, smoking, parity, and oral contraceptive use have been associated with an increased risk of cervical intraepithelial neoplasia grade 3 (CIN3) and cervical cancer among women who are infected with oncogenic human papillomavirus (HPV). However, these potential risk factors have not been adequately studied in prospective studies. Methods: We studied 1812 women who were enrolled in a 10-year prospective study of cervical neoplasia at Kaiser Permanente in Portland, Oregon, and who at enrollment had tested positive for oncogenic HPV DNA and had responded to a questionnaire that included questions on smoking, oral contraceptive use, and parity. Absolute risks and crude relative risks (RRs) with 95% confidence intervals (CIs) for CIN3 or cervical cancer were computed for three time intervals (0-8, 9-68, and 69-122 months after enrollment) using the Kaplan-Meier method. Conditional logistic regression models were used to control for factors that may have influenced our risk estimates, specifically the cytologic interpretation of baseline Pap smear, number of Pap smears during follow-up, age at enrollment, age at prediagnosis visit, and age at diagnosis. All statistical tests were two-sided. Results: Oral contraceptive use and parity were not associated with risk of CIN3 or cervical cancer. Former smokers, women who smoked less than one pack of cigarettes per day, and women who smoked one or more packs per day had crude RRs for CIN3 or cervical cancer for the entire follow-up period of 2.1 (95% CI = 1.1 to 3.9), 2.2 (95% CI = 1.2 to 4.2), and 2.9 (95% CI = 1.5 to 5.6), respectively, compared with never smokers. In the multi-variable model, former smokers, women who smoked less than one pack/day, and women who smoked one or more packs/day had RRs of 3.3 (95% CI = 1.6 to 6.7), 2.9 (95% CI = 1.4 to 6.1), and 4.3 (95% CI = 2.0 to 9.3), respectively, for CIN3 or cervical cancer compared with never smokers. Conclusions: Smoking is associated with an increased risk of invasive cervical cancer in women who are infected with oncogenic HPV. Subsequent studies should examine the role of smoking in the multistage pathogenesis of cervical cancer.

Original languageEnglish (US)
Pages (from-to)1406-1414
Number of pages9
JournalJournal of the National Cancer Institute
Volume94
Issue number18
StatePublished - Sep 18 2002
Externally publishedYes

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Uterine Cervical Neoplasms
Cervical Intraepithelial Neoplasia
Prospective Studies
Confidence Intervals
Neoplasms
Oral Contraceptives
Parity
Smoking
Papanicolaou Test
Logistic Models
Tobacco Products
Case-Control Studies
DNA

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Castle, P. E., Wacholder, S., Lorincz, A. T., Scott, D. R., Sherman, M. E., Glass, A. G., ... Schiffman, M. (2002). A prospective study of high-grade cervical neoplasia risk among human papillomavirus-infected women. Journal of the National Cancer Institute, 94(18), 1406-1414.

A prospective study of high-grade cervical neoplasia risk among human papillomavirus-infected women. / Castle, Philip E.; Wacholder, Sholom; Lorincz, Attila T.; Scott, David R.; Sherman, Mark E.; Glass, Andrew G.; Rush, Brenda B.; Schussler, John E.; Schiffman, Mark.

In: Journal of the National Cancer Institute, Vol. 94, No. 18, 18.09.2002, p. 1406-1414.

Research output: Contribution to journalArticle

Castle, PE, Wacholder, S, Lorincz, AT, Scott, DR, Sherman, ME, Glass, AG, Rush, BB, Schussler, JE & Schiffman, M 2002, 'A prospective study of high-grade cervical neoplasia risk among human papillomavirus-infected women', Journal of the National Cancer Institute, vol. 94, no. 18, pp. 1406-1414.
Castle, Philip E. ; Wacholder, Sholom ; Lorincz, Attila T. ; Scott, David R. ; Sherman, Mark E. ; Glass, Andrew G. ; Rush, Brenda B. ; Schussler, John E. ; Schiffman, Mark. / A prospective study of high-grade cervical neoplasia risk among human papillomavirus-infected women. In: Journal of the National Cancer Institute. 2002 ; Vol. 94, No. 18. pp. 1406-1414.
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title = "A prospective study of high-grade cervical neoplasia risk among human papillomavirus-infected women",
abstract = "Background: In case-control studies, smoking, parity, and oral contraceptive use have been associated with an increased risk of cervical intraepithelial neoplasia grade 3 (CIN3) and cervical cancer among women who are infected with oncogenic human papillomavirus (HPV). However, these potential risk factors have not been adequately studied in prospective studies. Methods: We studied 1812 women who were enrolled in a 10-year prospective study of cervical neoplasia at Kaiser Permanente in Portland, Oregon, and who at enrollment had tested positive for oncogenic HPV DNA and had responded to a questionnaire that included questions on smoking, oral contraceptive use, and parity. Absolute risks and crude relative risks (RRs) with 95{\%} confidence intervals (CIs) for CIN3 or cervical cancer were computed for three time intervals (0-8, 9-68, and 69-122 months after enrollment) using the Kaplan-Meier method. Conditional logistic regression models were used to control for factors that may have influenced our risk estimates, specifically the cytologic interpretation of baseline Pap smear, number of Pap smears during follow-up, age at enrollment, age at prediagnosis visit, and age at diagnosis. All statistical tests were two-sided. Results: Oral contraceptive use and parity were not associated with risk of CIN3 or cervical cancer. Former smokers, women who smoked less than one pack of cigarettes per day, and women who smoked one or more packs per day had crude RRs for CIN3 or cervical cancer for the entire follow-up period of 2.1 (95{\%} CI = 1.1 to 3.9), 2.2 (95{\%} CI = 1.2 to 4.2), and 2.9 (95{\%} CI = 1.5 to 5.6), respectively, compared with never smokers. In the multi-variable model, former smokers, women who smoked less than one pack/day, and women who smoked one or more packs/day had RRs of 3.3 (95{\%} CI = 1.6 to 6.7), 2.9 (95{\%} CI = 1.4 to 6.1), and 4.3 (95{\%} CI = 2.0 to 9.3), respectively, for CIN3 or cervical cancer compared with never smokers. Conclusions: Smoking is associated with an increased risk of invasive cervical cancer in women who are infected with oncogenic HPV. Subsequent studies should examine the role of smoking in the multistage pathogenesis of cervical cancer.",
author = "Castle, {Philip E.} and Sholom Wacholder and Lorincz, {Attila T.} and Scott, {David R.} and Sherman, {Mark E.} and Glass, {Andrew G.} and Rush, {Brenda B.} and Schussler, {John E.} and Mark Schiffman",
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AU - Castle, Philip E.

AU - Wacholder, Sholom

AU - Lorincz, Attila T.

AU - Scott, David R.

AU - Sherman, Mark E.

AU - Glass, Andrew G.

AU - Rush, Brenda B.

AU - Schussler, John E.

AU - Schiffman, Mark

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N2 - Background: In case-control studies, smoking, parity, and oral contraceptive use have been associated with an increased risk of cervical intraepithelial neoplasia grade 3 (CIN3) and cervical cancer among women who are infected with oncogenic human papillomavirus (HPV). However, these potential risk factors have not been adequately studied in prospective studies. Methods: We studied 1812 women who were enrolled in a 10-year prospective study of cervical neoplasia at Kaiser Permanente in Portland, Oregon, and who at enrollment had tested positive for oncogenic HPV DNA and had responded to a questionnaire that included questions on smoking, oral contraceptive use, and parity. Absolute risks and crude relative risks (RRs) with 95% confidence intervals (CIs) for CIN3 or cervical cancer were computed for three time intervals (0-8, 9-68, and 69-122 months after enrollment) using the Kaplan-Meier method. Conditional logistic regression models were used to control for factors that may have influenced our risk estimates, specifically the cytologic interpretation of baseline Pap smear, number of Pap smears during follow-up, age at enrollment, age at prediagnosis visit, and age at diagnosis. All statistical tests were two-sided. Results: Oral contraceptive use and parity were not associated with risk of CIN3 or cervical cancer. Former smokers, women who smoked less than one pack of cigarettes per day, and women who smoked one or more packs per day had crude RRs for CIN3 or cervical cancer for the entire follow-up period of 2.1 (95% CI = 1.1 to 3.9), 2.2 (95% CI = 1.2 to 4.2), and 2.9 (95% CI = 1.5 to 5.6), respectively, compared with never smokers. In the multi-variable model, former smokers, women who smoked less than one pack/day, and women who smoked one or more packs/day had RRs of 3.3 (95% CI = 1.6 to 6.7), 2.9 (95% CI = 1.4 to 6.1), and 4.3 (95% CI = 2.0 to 9.3), respectively, for CIN3 or cervical cancer compared with never smokers. Conclusions: Smoking is associated with an increased risk of invasive cervical cancer in women who are infected with oncogenic HPV. Subsequent studies should examine the role of smoking in the multistage pathogenesis of cervical cancer.

AB - Background: In case-control studies, smoking, parity, and oral contraceptive use have been associated with an increased risk of cervical intraepithelial neoplasia grade 3 (CIN3) and cervical cancer among women who are infected with oncogenic human papillomavirus (HPV). However, these potential risk factors have not been adequately studied in prospective studies. Methods: We studied 1812 women who were enrolled in a 10-year prospective study of cervical neoplasia at Kaiser Permanente in Portland, Oregon, and who at enrollment had tested positive for oncogenic HPV DNA and had responded to a questionnaire that included questions on smoking, oral contraceptive use, and parity. Absolute risks and crude relative risks (RRs) with 95% confidence intervals (CIs) for CIN3 or cervical cancer were computed for three time intervals (0-8, 9-68, and 69-122 months after enrollment) using the Kaplan-Meier method. Conditional logistic regression models were used to control for factors that may have influenced our risk estimates, specifically the cytologic interpretation of baseline Pap smear, number of Pap smears during follow-up, age at enrollment, age at prediagnosis visit, and age at diagnosis. All statistical tests were two-sided. Results: Oral contraceptive use and parity were not associated with risk of CIN3 or cervical cancer. Former smokers, women who smoked less than one pack of cigarettes per day, and women who smoked one or more packs per day had crude RRs for CIN3 or cervical cancer for the entire follow-up period of 2.1 (95% CI = 1.1 to 3.9), 2.2 (95% CI = 1.2 to 4.2), and 2.9 (95% CI = 1.5 to 5.6), respectively, compared with never smokers. In the multi-variable model, former smokers, women who smoked less than one pack/day, and women who smoked one or more packs/day had RRs of 3.3 (95% CI = 1.6 to 6.7), 2.9 (95% CI = 1.4 to 6.1), and 4.3 (95% CI = 2.0 to 9.3), respectively, for CIN3 or cervical cancer compared with never smokers. Conclusions: Smoking is associated with an increased risk of invasive cervical cancer in women who are infected with oncogenic HPV. Subsequent studies should examine the role of smoking in the multistage pathogenesis of cervical cancer.

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