The health and economic effects of HPV DNA screening in The Netherlands

Abstract

We studied the health and economic effects of human papillomavirus (HPV) DNA testing in cervical screening using a simulation model. The key data source was a Dutch longitudinal screening trial. We compared cytological testing with repeat cytology (for borderline/mildly abnormal smears) to HPV testing with cytology triage (for HPV-positive smears), combination testing (combined HPV and cytology) and cytological testing with HPV triage (for borderline/mildly abnormal smears). We varied the screening interval from 5 to 10 years. The main outcome measures were the number of cervical cancer cases, the number of quality-adjusted life years (QALYs), and the incremental cost-effectiveness ratio (ICER). The base-case estimates were accompanied with ranges across 118 calibrated parameter settings (calibration criteria: cervical intraepithelial neoplasia 2/3, cancer and mortality rates). In comparison to 5-yearly cytology, 5-yearly HPV testing with cytology triage gave a reduction in the number of cancer cases of 23% (range, 9-27%). The reduction was 26% (range, 10-29%) for combination testing and 3% (range, 21 to 8%) for cytology with HPV triage. For strategies with primary HPV testing, the model also estimated a reduction in cancer cases when the screening interval was extended to 7.5 years. Five-yearly cytology with HPV triage and 5 to 7.5-yearly HPV testing with cytology triage were cost effective for the base-case settings and the majority of calibrated parameter settings (ICER below Dutch willingness-to-pay threshold of €20,000/QALY). Our model indicates that HPV testing with cytology triage is likely to be cost effective. An extension of the screening interval may be considered to control costs.Since the implementation of screening, the incidence of cervical cancer has markedly decreased in developed countries. A further reduction is anticipated in the future as vaccines are now available that protect against infection with HPV types 16 and 18.1-3 Because the HPV vaccines only have a prophylactic effect, they are expected to be the most effective when given before the start of sexual activity. For older nonvaccinated women, screening will remain the most important instrument for cervical cancer prevention.The primary screening modality presently used in cervical screening is the Pap test. Although this test has formed the basis for successful screening programs (e.g., in the UK, Finland, Sweden and The Netherlands), its sensitivity is limited and the use of a more sensitive test such as the human papillomavirus (HPV) DNA test 4,5 may lead to a further reduction in the cervical cancer incidence. Several longitudinal trials have been started in the last 10 years, comparing the Pap test to the HPV test or a combination of both tests. [6][7][8][9][10][11] The first analyses have demonstrated that HPV testing in women more than 30 years of age detects more high-grade cervical intraepithelial neoplasia or cancer (CIN2þ) than cytology and that the CIN2þ risk is lower after an HPV-negative result at the previous screening ...

A Systematic Review of Economic Aspects of Cervical Cancer Screening Strategies Worldwide: Discrepancy between Economic Analysis and Policymaking

“…Methods for calculating the ICER in six articles were; cost/ QALY (Mandelblatt et al, 2002b, Berkhof et al, 2010Chuck, 2010;Chow et al, 2010;Vijayaraghavan et al, 2009;2010a), in 13 studies the ICER were estimated by cost/LYG (Brown and Garber, 1999;Maxwell et al, 2002;Mandelblatt et al, 2002a;Goldie et al, 2001;2004;Kim et al, 2005;Bidus et al, 2006;Andres-Gamboa et al, 2008;Kulasingam et al, 2009;Levin et al, 2010;Sroczynski et al, 2011;Burger et al, 2012). Two studies did not report their ICER (Bistoletti et al, 2008;de Kok et al, 2012).…”

“…Chuck et al remarked that Pap smear screening every three years for all Canadian women and HPV triage for women older than 30 years with ASCUS were the most cost-effective strategies (Chuck, 2010 (Maxwell et al, 2002;Bidus et al, 2006). Berkhof et al (2010) in the Netherlands, indicated that starting screening with HPV triage with 5 years interval was the most cost effective strategies (Berkhof et al, 2010).Vijayaraghavan in South Africa reported that coscreening with HPV testing was less costly and the most effective strategy (Vijayaraghavan et al, 2009). Based on income we just found 5 articles in high income countries suggested starting age of screening below age 30 (Mandelblatt et al, 2002b;Kulasingam et al, 2009;Chuck, 2010;Vijayaraghavan et al, 2010a;Sroczynski et al, 2011)(Table1).…”

“…Burger in Norway, suggested screening with cytology for younger women and HPV DNA testing strategy every four years after the age of 34 years (Burger et al, 2012). Seven papers suggested a five-year interval with various strategies such as HPV DNA testing (Andres-Gamboa et al, 2008;Kulasingam et al, 2009;Levin et al, 2010), HPV DNA triage (Berkhof et al, 2010;Chow et al, 2010), and primary HPV DNA in both types of co-screening or triage (de Kok et al, 2012). Mandelblatt suggested VIA with immediate treatment every five years as the most costeffective method in Thailand (Mandelblatt et al, 2002b).…”

“…Six articles proposed 3-5 years interval (Brown and Garber, 1999;Maxwell et al, 2002;Kim et al, 2005;Chuck, 2010;Vijayaraghavan et al, 2010b;Burger et al, 2012) and three articles showed that 5 years interval between screenings was cost effective (Kulasingam et al, 2009;Berkhof et al, 2010;de Kok et al, 2012). We just found one article in Sweden indicating that 9 years interval was cost effective (Bistoletti et al, 2008)…”

“…Fourteen studies were categorized as a high income countries (Brown and Garber, 1999;Mandelblatt et al, 2002b;Maxwell et al, 2002;Goldie et al, 2004;Kim et al, 2005;Bidus et al, 2006;Bistoletti et al, 2008;Kulasingam et al, 2009;Berkhof et al, 2010;Chuck, 2010;Vijayaraghavan et al, 2010a;Sroczynski et al, 2011;Burger et al, 2012;de Kok et al, 2012). Six studies were designed in middle income countries (Goldie et al, 2001;Maxwell et al, 2002;Andres-Gamboa et al, 2008;Vijayaraghavan et al, 2009;Chow et al, 2010;Levin et al, 2010).…”