Type-specific persistence of human papillomavirus DNA before the development of invasive cervical cancer

N Engl J Med. 1999 Nov 25;341(22):1633-8. doi: 10.1056/NEJM199911253412201.


Background: Infection with the human papillomavirus (HPV) has been established as a cause of cervical cancer, but the association between a positive test for HPV DNA and the risk of the subsequent development of invasive cervical cancer is unknown.

Methods: In a study of women who participated in a population-based screening program for cancer of the cervix in Sweden from 1969 to 1995, we compared the proportion of normal cervical smears (Pap smears) that were positive for HPV DNA among 118 women in whom invasive cervical cancer developed an average of 5.6 years later (range, 0.5 month to 26.2 years) with the proportion of HPV DNA-positive smears from 118 women who remained healthy during a similar length of follow-up (controls). The control women were matched for age to the women with cancer, and they had had two normal Pap smears obtained at time points that were similar to the times of the baseline smear and the diagnosis of cancer confirmed by biopsy in the women with cancer.

Results: At baseline, 35 of the women with cancer (30 percent) and 3 of the control women (3 percent) were positive for HPV DNA (odds ratio, 16.4; 95 percent confidence interval, 4.4 to 75.1). At the time of diagnosis, 80 of the 104 women with cancer for whom tissue samples were available (77 percent) and 4 of the 104 matched control women (4 percent) were positive for HPV DNA. The HPV DNA type was the same in the base-line smear and the biopsy specimen in all of the women with cancer in whom HPV DNA was detected at base line. None of the control women had the same type of HPV in both smears.

Conclusions: A single positive finding of HPV DNA in a Pap smear confers an increased risk of future invasive cervical cancer that is positive for the same type of virus as identified earlier.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / etiology
  • Adenocarcinoma / pathology
  • Adenocarcinoma / virology
  • Adult
  • Carcinoma, Squamous Cell / etiology
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / virology
  • Case-Control Studies
  • Cervix Uteri / virology*
  • Chronic Disease
  • DNA, Viral / analysis*
  • Female
  • Humans
  • Middle Aged
  • Neoplasm Invasiveness
  • Papanicolaou Test
  • Papillomaviridae / classification
  • Papillomaviridae / genetics
  • Papillomaviridae / isolation & purification*
  • Papillomavirus Infections / complications*
  • Population Surveillance
  • Prospective Studies
  • Risk Factors
  • Sensitivity and Specificity
  • Tumor Virus Infections / complications*
  • Uterine Cervical Neoplasms / etiology*
  • Uterine Cervical Neoplasms / pathology
  • Uterine Cervical Neoplasms / virology
  • Vaginal Smears


  • DNA, Viral