Prevaccination Distribution of Human Papillomavirus Types in Women Attending at Cervical Cancer Screening in Belgium Marc Arbyn, 1 Ina Benoy, 2 Cindy Simoens, 1 Johannes Bogers, 3 Philippe Beutels, 4 and Christophe Depuydt 2 1 Unit of Cancer Epidemiology, Scientific Institute of Public Health, Brussels, Belgium; 2 Laboratory for Clinical Pathology (labo RIATOL); 3 AMBIOR, Laboratory for Cell Biology and Histology, and 4 Unit Health Economics and Modelling Infectious Diseases, Vaccine and Infectious Disease Institute, University of Antwerp, Antwerp, Belgium Abstract Introduction: Before the introduction of vaccination against human papillomaviruses (HPV) as a new strategy of combating cervical cancer, it is required to describe the baseline prevalence of HPV infection as well as the distribution of the different HPV types in the population and among women with cervical lesions. Materials and Methods: Approximately 10,000 liquid cervicalcellsamplesfromwomen,residentofFlanders (North Belgium) and participating in cervical cancer screening,wereassessedcytologicallyandvirologically withamultiplexreal-timePCRusingprimerstargeting the E6/E7 genes of 16 HPV types. Correlations of HPV infection with age, geographic area, and occurrence of cytologic lesions were assessed. Results: The prevalence of cytologic abnormalities was atypical squamous cells of undetermined significance (ASC-US), 1.6%; atypical glandular cells (AGC), 0.2%; low-grade squamous intraepithelial lesion (LSIL), 2.6%; atypical squamous cells, HSIL cannot be excluded (ASC-H), 0.3%; and high-grade squamous intraepithelial lesion (HSIL), 1.2%. The frequency of high-risk HPV infections was 11% in women without cytologic abnormalities, 77% in ASC-US, 32% in AGC, 85% in LSIL, and 93% in ASC-H and HSIL. The prevalence of high-risk HPV infection was highest in women of ages 20 to 24 years (29%) and decreased progressivelywithage.Thepercentageofwomenwith HSIL in the entire study population attributable to infection with a particular type (AR pop %) was highest for HPV16 (32%), followed by HPV31 (22%), HPV39 (11%), and HPV52 (11%). HPV18 was responsible for 7% of the HSIL lesions. Elimination of HPV16 and HPV18isexpectedtoreducetheprevalenceofASCUS with 24%, AGC with 19%, LSIL with 29%, ASC-H with 31% and HSIL with 37%. Discussion: Compared to other West European studies, the prevalence of HPV infection was considerably higher in cytologically negative women but similar in women with cervical lesions. These differences could be due to the use of a PCR with high analytic sensitivity. These data are relevant for estimating the expected and theoretical levels of vaccine protection offered as vaccinated girls gradually age into the groups from which our observations stem. Further periodic laboratory-based surveys, including genotyping of cervical cell samples and linkage with vaccine registries, are an important resource to address pending questions of the effect of HPV vaccination. Research is warranted to disentangle the causal role of individual HPV types in case of multiple infections. (Cancer Epidemiol Biomarkers Prev 2009;18(1):321–30) Introduction The recognition of the strong causal relation between persistent infection of the genital tract with oncogenic human papillomavirus (HPV) types and the occurrence of cervical cancer precursors and cervical cancer has resulted in the development of tests for HPV nucleic acid detection (1, 2). Such tests can be used in primary screening for cervical cancer, for triage of women with atypical or borderline cervical smears, or for surveillance after treatment of cervical intraepithelial neoplasia (3-5). Prophylactic vaccination with the L1 capsid proteins elicits the production of virus neutralizing antibodies that protect against persistent infection and high-grade cervical, vaginal, and vulvar neoplasia caused by the HPV types included in the vaccine (6-9). In 2006, the use of a quadrivalent vaccine containing L1 virus-like particles of HPV types 6, 11, 16, and 18 was licensed by the U.S. Food and Drug Administration and authorized for marketing by the European Medicines Agency. A bivalent vaccine containing L1 from HPV types 16 and 18 was licensed more recently by the European Medi- cinesAgencyaswell,buttodate,notyetbytheFoodand Drug Administration. Cancer Epidemiol Biomarkers Prev 2009;18(1). January 2009 Received 6/3/08; revised 9/23/08; accepted 10/16/08. Grant support: European Commission (Directorate of SANCO, Luxembourg, Grand-Duche ´ du Luxembourg), through the European Network for Information on Cancer Epidemiology (EUNICE, coordinated by IARC, Lyon); the European Research Network of Excellence Cancer Control using Population Registries and Biobanking , funded by the 6th Framework programme (Brussels, Belgium) through the University of Lund (Malmo ¨, Sweden); Belgian Cancer Foundation (Belgische Stichting tegen Kanker), (Brussels, Belgium); and IWT (Institute for the Promotion of Innovation by Science and Technology in Flanders), as part of ‘‘SIMID,’’ a strategic basic research project, project no. 060081. Requests for reprints: Marc Arbyn, Unit of Cancer Epidemiology, Scientific Institute of Public Health, J. Wytsmanstreet 14, BE-1050 Brussels, Belgium. Phone: 32-642-5021; Fax: 32-642-5410. E-mail: marc.arbyn@iph.fgov.be Copyright D 2009 American Association for Cancer Research. doi:10.1158/1055-9965.EPI-08-0510 321 on May 20, 2020. © 2009 American Association for Cancer Research. cebp.aacrjournals.org Downloaded from