Targeting human papillomavirus to reduce the burden of cervical, vulvar and vaginal cancer and pre-invasive neoplasia: establishing the baseline for surveillance

PLoS One. 2014 Feb 5;9(2):e88323. doi: 10.1371/journal.pone.0088323. eCollection 2014.


Background: Infection with high-risk human papillomavirus (HPV) is causally related to cervical, vulvar and vaginal pre-invasive neoplasias and cancers. Highly effective vaccines against HPV types 16/18 have been available since 2006, and are currently used in many countries in combination with cervical cancer screening to control the burden of cervical cancer. We estimated the overall and age-specific incidence rate (IR) of cervical, vulvar and vaginal cancer and pre-invasive neoplasia in Denmark, Iceland, Norway and Sweden in 2004-2006, prior to the availability of HPV vaccines, in order to establish a baseline for surveillance. We also estimated the population attributable fraction to determine roughly the expected effect of HPV16/18 vaccination on the incidence of these diseases.

Methods: Information on incident cervical, vulvar and vaginal cancers and high-grade pre-invasive neoplasias was obtained from high-quality national population-based registries. A literature review was conducted to define the fraction of these lesions attributable to HPV16/18, i.e., those that could be prevented by HPV vaccination.

Results: Among the four countries, the age-standardised IR/10⁵ of cervical, vaginal and vulvar cancer ranged from 8.4-13.8, 1.3-3.1 and 0.2-0.6, respectively. The risk for cervical cancer was highest in women aged 30-39, while vulvar and vaginal cancers were most common in women aged 70+. Age-standardised IR/10⁵ of cervical, vulvar and vaginal pre-invasive neoplasia ranged between 138.8-183.2, 2.5-8.8 and 0.5-1.3, respectively. Women aged 20-29 had the highest risk for cervical pre-invasive neoplasia, while vulvar and vaginal pre-invasive neoplasia peaked in women aged 40-49 and 60-69, respectively. Over 50% of the observed 47,820 incident invasive and pre-invasive cancer cases in 2004-2006 can be attributed to HPV16/18.

Conclusion: In the four countries, vaccination against HPV 16/18 could prevent approximately 8500 cases of gynecological cancer and pre-cancer annually. Population-based cancer and vaccination registries are essential to assess the predicted public health effects of HPV vaccination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Cervix Uteri / pathology
  • Cervix Uteri / virology
  • Female
  • Human papillomavirus 16 / isolation & purification
  • Human papillomavirus 18 / isolation & purification
  • Humans
  • Incidence
  • Middle Aged
  • Papillomavirus Infections / epidemiology
  • Papillomavirus Infections / prevention & control
  • Papillomavirus Infections / virology
  • Papillomavirus Vaccines / therapeutic use*
  • Uterine Cervical Neoplasms / epidemiology
  • Uterine Cervical Neoplasms / pathology
  • Uterine Cervical Neoplasms / prevention & control*
  • Uterine Cervical Neoplasms / virology*
  • Vagina / pathology
  • Vagina / virology
  • Vaginal Neoplasms / epidemiology
  • Vaginal Neoplasms / pathology
  • Vaginal Neoplasms / prevention & control*
  • Vaginal Neoplasms / virology*
  • Vulva / pathology
  • Vulva / virology
  • Vulvar Neoplasms / epidemiology
  • Vulvar Neoplasms / pathology
  • Vulvar Neoplasms / prevention & control*
  • Vulvar Neoplasms / virology*
  • Young Adult


  • Papillomavirus Vaccines

Grant support

Financial support from Merck & Co., Inc. (research grant EPO 8014.033) has been received. The registry data used in the current article were obtained from population-based registries that are funded by governments and non-profit cancer societies. Each country collected and analyzed data independently from the funding company as described in the Methods section. The lead author drafted the manuscript. KLL and ED are employees of the funding company and participated with the other coauthors in discussions of study design and manuscript revision. Anonymous data from the population-based registries are publicly available. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.