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

Abstract

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.

Figure 1. Incidence rates/10⁵ of cervical (A), vulvar (B) and vaginal (C) cancer in 2004–2006, by age and country.

The y-axis shows incidence rates per 100,000 person years on a log scale and the x-axis represents age group. Blue, red, green, and violet lines refer to Denmark, Iceland, Norway and Sweden, respectively. Country specific point-estimates for incidence rate per 100,000 are given in a four-row table below each panel, by age-groups: 0–19, 20–29, 30–39, 40–49, 50–59, 60–69 and 70 years and over.

Figure 2. Incidence rates/10⁵ of cervical (A), vulvar (B) and vaginal (C) pre-invasive neoplasia in 2004–2006, by age and country.

The y-axis shows incidence rates per 100,000 person years on a log scale and the x-axis represents age group. Blue, red, green, and violet lines refer to Denmark, Iceland, Norway and Sweden, respectively. Country specific point-estimates for incidence rate per 100,000 are given in a four-row table below each panel, sorted by age-groups: 0–19, 20–29, 30–39, 40–49, 50–59, 60–69 and 70 years and over. From Sweden only vulvar and vaginal intraepithelial neoplasia grade 3 are included, whereas other countries include both grades 2 and 3.

Figure 3. Observed and hypothetical incidence rate per 100,000 woman years of cervical pre-invasive nepolasia (A) and cervical cancer (B) by age in four Nordic countries combined in 2004–2006.

The y-axis shows incidence rates per 100,000 person years and the x-axis represents age group. The solid line refers to observed incidence in 2004–2006; the long-dashed and short dashed line refers to expected incidence assuming the lowest and highest estimated HPV16/18 attributable fractions, respectively.