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

Mari Nygård,Joakim Dillner,Bo Terning Hansen,Maria Hortlund,Erik J Dasbach,Kai-Li Liaw,Kristján Oddsson,Christian Munk,Susanne Krüger Kjær,Laufey Tryggvadottir

doi:10.1371/journal.pone.0088323

Abstract

BackgroundInfection 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.MethodsInformation 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.ResultsAmong 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.ConclusionIn 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.

Highlights

Persistent infection with high-risk human papillomavirus types is a necessary cause of cervical cancer and pre-invasive neoplasia [1]
Hr human papillomavirus (HPV) types have been detected in virtually all cervical cancers and cervical intraepithelial neoplasia grades 2 and 3 (CIN2/3) [2,3,4]; in 40–70% of all vulvar and vaginal cancers, and in about 85–90% of vulvar intraepithelial neoplasia grades 2 and 3 (VIN2/3) and vaginal intraepithelial neoplasia grades 2 and
HPV16 has been reported to be present in 49–81% of CIN2/3, VIN2/3 and vaginal intraepithelial neoplasia grades 2 and3 (VaIN2/3), whereas only 2–14% of these lesions test positive for HPV18

Summary

Introduction

Persistent infection with high-risk human papillomavirus types (hrHPV) is a necessary cause of cervical cancer and pre-invasive neoplasia [1]. The reported proportions of specific HPV types detected in cervical, vulvar and vaginal cancer and pre-invasive neoplasias vary widely. Suggested explanations for this variation include differences in the sensitivity of the HPV detection methods used [8], global disparity in HPV type distribution, as well as the difficulties of taking into account the strong effect of age on HPV positivity rates in studies that included different age groups [9,10]. 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 estimated the population attributable fraction to determine roughly the expected effect of HPV16/18 vaccination on the incidence of these diseases

Methods

Results

Discussion

Conclusion