A cohort study of the risk of cervical intraepithelial neoplasia grade 2 or 3 in relation to papillomavirus infection

N Engl J Med. 1992 Oct 29;327(18):1272-8. doi: 10.1056/NEJM199210293271804.


Background: Human papillomavirus (HPV) has been associated with cervical intraepithelial neoplasia, but the temporal relation between the infection and the neoplasia remains unclear, as does the relative importance of the specific type of HPV, other sexually transmitted diseases, and other risk factors.

Methods: We studied prospectively a cohort of 241 women who presented for evaluation of sexually transmitted disease and had negative cervical cytologic tests. The women were followed every four months with cytologic and colposcopic examinations of the uterine cervix and tests for HPV DNA and other sexually transmitted diseases.

Results: Cervical intraepithelial neoplasia grade 2 or 3 was confirmed by biopsy in 28 women. On the basis of survival analysis, the cumulative incidence of cervical intraepithelial neoplasia at two years was 28 percent among women with a positive test for HPV and 3 percent among those without detectable HPV DNA: The risk was highest among those with HPV type 16 or 18 infection (adjusted relative risk as compared with that in women without HPV infection, 11; 95 percent confidence interval, 4.6 to 26; attributable risk, 52 percent). All 24 cases of cervical intraepithelial neoplasia grade 2 or 3 among HPV-positive women were detected within 24 months after the first positive test for HPV. After adjustment for the presence of HPV infection, the development of cervical intraepithelial neoplasia was also associated with younger age at first intercourse, the presence of serum antibodies to Chlamydia trachomatis, the presence of serum antibodies to cytomegalovirus, and cervical infection with Neisseria gonorrhoeae.

Conclusions: Cervical intraepithelial neoplasia is a common and apparently early manifestation of cervical infection by HPV, particularly types 16 and 18.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Cohort Studies
  • Condylomata Acuminata / complications
  • DNA, Viral / analysis
  • Female
  • Humans
  • Middle Aged
  • Papillomaviridae* / genetics
  • Papillomaviridae* / isolation & purification
  • Precancerous Conditions / etiology*
  • Prospective Studies
  • Risk Factors
  • Sexually Transmitted Diseases / complications
  • Time Factors
  • Tumor Virus Infections / complications*
  • Uterine Cervical Neoplasms / etiology*
  • Uterine Cervical Neoplasms / microbiology


  • DNA, Viral