Cigarette smoking, oncogenic human papillomavirus, Ki-67 antigen, and cervical intraepithellal neoplasia

Tiffany G. Harris, Shalini L. Kulasingam, Nancy B. Kiviat, Constance Mao, S. Nicholas Agoff, Qinghua Feng, Laura A. Koutsky

Research output: Contribution to journalArticlepeer-review

68 Scopus citations


Although cigarette smoking has been identified as a cofactor for cervical neoplasia, it is not clear whether smoking exerts an early or late effect on the evolution of human papillomavirus (HPV)-related lesions. A case-control study of Washington State women who presented for routine gynecologic care from 1997 to 2001 was conducted. All women underwent cytologic testing and HPV DNA screening. Those with abnormal cytology findings or a positive oncogenic HPV test and a random sample of women negative on both tests were referred for colposcopically directed cervical biopsy with repeated testing. Among 461 women with oncogenic HPV were 181 controls with negative histology, 137 cases with histologically confirmed cervical intraepithelial neoplasia (CIN) grade 1 (CIN1), and 143 cases with histologically confirmed CIN grades 2-3 or higher (≥CIN2-3). Smoking information was obtained by questionnaire. Immunohistochemistry testing for Ki-67 was performed on a subset of biopsy specimens (n = 139). Smoking 10 or more cigarettes per day was associated with ≥CIN2-3 (adjusted odds ratio = 2.6, 95% confidence interval: 1.3, 5.5) and CIN1 (adjusted odds ratio = 2.5, 95% confidence interval: 1.2, 5.3). Heavy smoking was positively associated with Ki-67 but not with repeated detection of oncogenic HPV. Since smoking was associated with both CIN1 and ≥CIN2-3, cigarette by-products may affect the early evolution of HPV-related lesions, possibly by increasing the rate of cell turnover.

Original languageEnglish (US)
Pages (from-to)834-842
Number of pages9
JournalAmerican journal of epidemiology
Issue number9
StatePublished - May 1 2004

Bibliographical note

Funding Information:
This work was supported by Public Health Service grant CA34493 from the National Cancer Institute.


  • Case-control studies
  • Cervical intraepithelial neoplasia
  • Cervix uteri
  • Female
  • Ki-67 antigen
  • Papillomavirus, human
  • Smoking
  • Tobacco smoke pollution


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