Prevalence of HPV Infection Using Self-sampling Screening and Monitoring the Earlier Impact of HPV-Vaccination Program in Switzerland
Conditions: HPV - Anogenital Human Papilloma Virus Infection
Sponsor: University Hospital, Geneva

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Prevalence of HPV infection using self-sampling screening and 
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monitoring the Earlier Impact of HPV-Vaccination Program in 
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Switzerland 
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Study protocol – version 5 
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 08 june 2016 
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
Principal Investigator: Pr Patrick Petignat, MD, University Hospitals of Geneva,
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Head of Gynecologic Division, CH-1211 Geneva 14, patrick.petignat@hcuge.ch
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Co- investigators:
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Emilien Jeannot, Msc, MPH, PhD cand. Institute of Global Health, Department of Health and 
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Community Medicine, University of Geneva and University of Applied Sciences Western 
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Switzerland, Geneva, Switzerland Mail : Emilien.Jeannot@unige.ch 
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Dr. Pierre Vassilakos, MD, Geneva Foundation for Medical Education and Research, 
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pierrevassilakos@bluewin.ch  
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Dr. Rosa Catarino MD, University Hospitals of Geneva, Head of Gynecologic Division, CH-
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1211 Geneva 14, RosaIsabel.PintoCatarino@hcuge.ch. 
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Dr. Manuela Viviano, University Hospitals of Geneva, Head of Gynecologic Division, CH-
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1211 Geneva 14, Manuela.Viviano@hcuge.ch 
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Pr Emmanuel Kalenbele, PhD, Institute of Global Health, Department of Health and 
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Community Medicine, University of Geneva, Emmanuel.Kabengele@unige.ch 
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Abstract 
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Background: Currently prevalence of HPV infections for high risk strains among young 
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women in Switzerland is unknown. In addition, since 2008 a vaccination program to prevent 
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these infections has been implemented in a number of cantons, but its actual population 
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impact is currently unknown. For now, HPV screening in Switzerland is mainly performed by 
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gynecologists or during gynecological consultation at hospital. This method is certainly 
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effective, but expensive; population coverage of screening is still insufficient. A whole 
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segment of the target population does not participate in this screening especially young 
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people of foreign origin, for various reasons: economic cost, no gynecological, and for other 
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reasons. 
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Several studies raise the effectiveness and efficiency of self-sampling to increase coverage 
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of screening, and the rate of participation of non-participants. Through this study, we 
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evaluate the possibility to use self-sampling as a screening tool in a real population, 
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document the effectiveness of this vaccination on the prevalence of HPV infections and 
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assess evolution of infection and clearance of HPV virus during 5 years in a population of 
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young unvaccinated and vaccinated girls. 
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Method: During the study, each woman will perform a vaginal swab sampling by auto to 
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research HPV. These samples will be sent to a laboratory where HPV typing is done by PCR 
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using 
the 
Anyplex 
™ 
II 
technology. 
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The study will focus on a sample of 400 young women. Participants must complete a 
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questionnaire containing demographic questions and their HPV immunization status. 
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Vaccination coverage expected in this population is about 50%. Depending on the state of 
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vaccination, two different groups will be vaccinated vs unvaccinated (200 women per group). 
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The cases of HPV infection are then calculated for each group and compared as a function 
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of the status of vaccination. Statistical tests will be applied McNemar's test for comparison 
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between 
the 
HPV 
prevalence 
rates 
between 
the 
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groups. 
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Expected Results: This study will allow us to confirm the possibility of using self-sampling 
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as a method of screening and monitoring of HPV infections in the general population, it will 
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also enable us to document the effectiveness of HPV vaccination by comparing prevalence 
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rate of HPV infections among a group of young girls vaccinated and not vaccine and assess 
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evolution of infection and clearance of HPV virus. 
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Key words: cervical cancer, self-sampling, Human papillomavirus (HPV) 
 
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1. Background 
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Human papillomavirus (HPV) vaccination to prevent cervical cancer has been introduced in 
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Switzerland in 2008. Recommendations are that young girls aged 11 to 14 are included in 
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the immunization schedule program at school and girls aged 15 to 19 are included in a 
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“catch-up program”, for a transition period, until 2012. Within school-based program, the 
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vaccine uptake has been achieved to date with a 60% course completion, but lower rate 
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(20%) has been observed in cantons having adopted an “opportunistic” vaccination strategy. 
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Monitoring public health impact is an essential component of the intervention. Since the 
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eventual cervical cancer disease reduction will be only able to be evaluated decades after 
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exposure, current monitoring activity will focus on the anticipated earlier reduction of HPV 
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vaccine-type in the population. In 2015, seven years passed since the first vaccinated 
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cohorts entered the program; “school-vaccinated” women will be of 18 years old and “catch-
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up vaccination” will be of 32 years old. Prior introduction of the vaccine in Switzerland, the 
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only available data was from HPV testing performed with residual cervical screening sample 
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from women attending cervical cancer screening (1, 2). To date, there is no Swiss available 
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data about the impact of HPV vaccination. The earlier sign of HPV vaccination could 
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probably be observed on the HPV prevalence and precursor lesion in women population. To 
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date, there is no Swiss available data about the impact of HPV vaccination. The earlier sign 
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of HPV vaccination could probably be observed on the HPV prevalence and precursor lesion 
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in women population. An observational study conducted in Australia support that the 
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incidence of genital warts decreases in younger women (3-5). Another trial conducted in 
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England (6) has showed that the national HPV immunization program seemed successful in 
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preventing HPV 16/18 infection in sexually active young women. The prevalence of HPV 
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16/18 infection in the post-immunization survey was 6.5% amongst 16–18 year olds, 
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compared to 19.1% in the similar survey conducted prior to the introduction of HPV 
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immunization. 
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 In USA, the US population-based sentinel surveillance system to monitor HPV impact show 
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that from 2008 to 2012, prevalence of HPV 16/18 in CIN2+ lesions statistically significantly 
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decreased from 53.6% to 28.4% among women who received at least one dose HPV vaccine 
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(Ptrend<.001) but not among unvaccinated women (57.1% vs 52.5%; Ptrend=.08) or women 
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with unknown vaccination status (55.0% vs 50.5%; Ptrend=.71) (7). More recently, a 
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systematic review and meta-analysis describe that, in countries with female vaccination 
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coverage of at least 50%, HPV type 16 and 18 infections decreased significantly between the 
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pre-vaccination and post-vaccination periods by 68% (RR 0·32, 95% CI 0·19-0·52) and 
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anogenital warts decreased significantly by 61% (RR 0·39, 0·22-0·71) in girls 13-19 years of 
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age. Comparing to countries with female vaccination coverage lower than 50%, significant 
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reductions in HPV types 16 and 18 infection (RR 0·50, 95% CI 0·34-0·74]) and in anogenital 
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warts (0·86 [95% CI 0·79-0·94]) occurred in girls younger than 20 years of age, with no 
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indication of cross-protection or herd effects (8). 
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To evaluate the effectiveness of this vaccination, it is important to detect quickly, 
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economically and efficiently prevalence of HPV high risk in our population. In Switzerland, 
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young women who want to get tested do either with their gynecologists or so via 
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gynecological hospital visits. This method is certainly effective, but expensive, furthermore 
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screening coverage is still insufficient (only 30 to 40 % women’s don’t participle at the 
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screening) in Switzerland. Also a part of our study population don’t participate in screening 
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such young people of foreign origin for various reasons, no gynecological medecin, 
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economic 
cost 
etc 
... 
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Several studies raise the effectiveness and efficiency  (9) of the  self sampling to increase 
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screening coverage (10), participation rate of nonattenders (11, 12) self-sampling has been 
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nearly as sensitive as clinician-obtained cervical samples and more sensitive than cytology 
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for the detection of cervical intraepithelial neoplasia (CIN) for lesions of high-grade CIN-II or 
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higher (CIN-II+) (13-14) .  
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Through this study we want to evaluate the possibility of using self sampling as a screening 
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tool in a real population, yet a study in Geneva showed the possibility of its use for screening 
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a population not visiting gynecological hospital visits (15), but the actual population use 
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remains to be demonstrated. 
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2. Objectives 
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Through this study, we evaluate the possibility to use self sampling as a screening tool in a 
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real population, document the effectiveness of this vaccination on the prevalence of HPV 
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infections and assess evolution of infection and we will assess the evolution of viral 
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infection and clearance of throughout 5 years in a population of young, unvaccinated and 
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vaccinated girls. 
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Primary objective 
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 Explored the feasibility of establishing a home-based Self-HPV screening strategy in 
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general population 
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Secondary objective 
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To determine the HPV prevalence of vaccine-type: 19 high-risk HPV types (16, 18, 26, 
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31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68, 69, 73, 82) and 9 low-risk HPV types(6, 
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11, 40, 42, 43, 44, 54, 61, 70) in young women population attending High schools in 
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Geneva and Faculty of Medicine at the University of Geneva. 
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 To generate data about vaccination impact and vaccine coverage. 
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To assess the infection’s evolution and clearance of HPV throughout 5 years in a 
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population of young, unvaccinated and vaccinated young women 
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3. Material and method 
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Inclusion criteria: 
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 
Eligible women aged between 18-31 years attending of Haute Ecole de Santé – 
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Genève and Faculty of Medicine at the University of Geneva. 
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Understands study procedures and accepts voluntarily to participate by signing the 
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informed consent form (ICF) 
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Exclusion criteria: 
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History of hysterectomy or treatment on the cervix during the last 12 months. 
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Study Design and Methods 
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Setting: The study will be conducted in collaboration with the High school of health in Geneva 
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and Faculty of Medicine at the University of Geneva. The study will be proposed to 400 
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women attending these schools.  
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Recruitment: It will take place in the health school of health and Faculty of Medicine at the 
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University of Geneva. Trial information on the University website will be available; it will also 
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contain a phone number for helpline. Cards to check eligibility, registration and scheduling 
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will be available. The HPV self-collection kit will be directly distributed to participants at the 
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end of their courses to School of Health and University of Geneva School of Medicine 
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Data collection: Vaccination status, age, menopausal status, marital status, parity, tobacco 
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consumption, medical records, geographic data, consulting-date and HPV-test result. 
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HPV tests: The HPV self-collection kit included a dacron swab, collection tube, instructions 
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with explanatory pictures, consent forms and a participant demographic information. The 
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HPV analysis will be performed by Real-time PCR. Delay between sampling and lab 
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processing will be noted. 
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Technical aspect:  Written informed consent will be obtained by papier. All women will 
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perform a self sampling for HPV testing using a simple swab with no medium. The results of 
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HPV testing and sociodemographic data will be archived in a database. 
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Statistical analysis: The expected vaccination coverage in this population is about 50%. 
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According vaccination status, 2 different groups will be formed vaccinated vs non-
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vaccinated). The cases of HPV infection (status HPV+) will then be calculated for each group 
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and compared according to the vaccination status. The applied statistical tests will be 
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McNemar’s test for comparison. 
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Sample size:  Sample size was obtained based on estimated prevalence of 6% of HPV 16/18 
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infection in the Swiss population aged less than 30 years. A total of 200 specimens per group 
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would be needed to detect about an 85% reduction in HPV 16/18 prevalence (prevalence of 
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0.9% in the vaccinated population), given an 80% power and a two-sided significance level of 
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95% (based on representative data from England). We therefore estimate that a sample size 
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of 400 women (200 in each group) will be adequate for the analyses.  
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Follow up: Participants will receive their results by e-mail directly via our colposcopy nurse. 
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We will follow the HPV-positive participants every 6 months during 5 years to assess the 
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evolution of their HPV status and the viral clearance. In order to do this, every 6 months they 
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will receive a self-sampling sampling HPV kit at home, which they will return by mail to the 
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HUG for analysis. 
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4. Statement regarding the relevance and potential contribution of the project to 
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cancer control 
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Data from the registries will be used to assess the HPV prevalence of the pre-vaccine era 
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and will be the basis for monitoring infection after post-vaccine introduction. This study will 
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provide important data about the prevalence of HPV infection in a young and sexually active 
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population of women and on the proportion of vaccinated and non-vaccinated young women.  
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Despite the impact of vaccine on invasive cancers is not expected until some decades after 
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its extensive implementation, as the type-specific prevalence of HPV infection is very high in 
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young sexually active populations, the effect of a successful HPV vaccination program 
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should be quickly detected by sentinel surveillance in this sub-population. 
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Monitoring the impact of the vaccination programs by detecting type-specific infection is 
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important as it is the earliest anticipated change, and failure to detect protection from 
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infection will indicate failure to prevent cancer in the subsequent decades and allow the 
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implementation of appropriate changes in cervical cancer screening strategies. 
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This surveillance is required in order to document the expected gains in cancer prevention if 
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there is appropriate population coverage. In our case, no data is available in Switzerland.  
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Such surveillance would allow further studies to determine the duration of protection, long-
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term safety and actual impact on health-care cost consumption. 
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In this project, 400 young girls will know their statuses for HPV infection and will obtain 
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information about this prevalent infection and offered sexual counselling. Those who test 
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positive for HPV infection will be guided to a gynaecological consultation for adequate 
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management. 
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By using self-sampling for HPV testing, we will demonstrate the potential benefit in terms of 
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participation, lower cost and feasibility to determine the prevalence of infection. This method 
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is much easier and cheaper than the current cervical cancer screening test used (Pap test), 
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which requires a gynaecological consultation. The self-sampling could be used to increase 
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the participation of young women in the cervical cancer screening programs and thereby 
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increase the effectiveness of the overall program screening. 
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In conclusion, monitoring HPV prevalence among sexually active young women in different 
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selected settings will provide an important early indication of HPV vaccine impact. These 
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data will also contribute to add important information for cervical cancer screening.  
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5. Ethical issues 
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The investigators commit that this study will be conducted in accordance with the Swiss law, 
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as well as in accordance with the recommendations of Good Clinical Practices (ICH E6-
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1996) and the Declaration of Helsinki (Fortaleza, October 2013).Before the study starts, the 
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approval of the protocol by the Geneva Ethics Committee will be required, and all patients 
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will give their written informed consent to participate in the study. 
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All the participants will be informed of the HPV results and a webpage containing information 
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on the implications of having a positive result in women aged less than 30 years will be 
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available. Information can also be obtained via our colposcopy nurse (a helpline will be 
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available). 
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6. Financial consideration 
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This study includes no charge for the patients. Financial support was solicited for a 100% 
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research nurse for 12 months period (FRS 135’000), to buy kit sampling HPV (FRS 60) and 
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to Cepheid GeneXpert® System for HPV testing (equipment rental + Test cartridges) ( FRS 
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40’000).  
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7. References 
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1.Petignat P, Faltin D, Goffin F, Billieux MH, Stucki D, Sporri S, et al. Age-related performance of 
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human papillomavirus testing used as an adjunct to cytology for cervical carcinoma screening in a 
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population with a low incidence of cervical carcinoma. Cancer. 2005;105(3):126-32. 
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2. Bigras G, de Marval F. The probability for a Pap test to be abnormal is directly proportional to 
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HPV viral load: results from a Swiss study comparing HPV testing and liquid-based cytology to detect 
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cervical cancer precursors in 13,842 women. British journal of cancer. 2005;93(5):575-81. 
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3. Read TR, Hocking JS, Chen MY, Donovan B, Bradshaw CS, Fairley CK. The near disappearance 
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of genital warts in young women 4 years after commencing a national human papillomavirus (HPV) 
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vaccination programme. Sex Transm Infect. 2011;87(7):544-7. Epub 2011/10/06. 
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4. Donovan B, Franklin N, Guy R, Grulich AE, Regan DG, Ali H, et al. Quadrivalent human 
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papillomavirus vaccination and trends in genital warts in Australia: analysis of national sentinel 
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surveillance data. Lancet Infect Dis. 2011;11(1):39-44. Epub 2010/11/12. 
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5. Brotherton JM, Fridman M, May CL, Chappell G, Saville AM, Gertig DM. Early effect of the 
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HPV vaccination programme on cervical abnormalities in Victoria, Australia: an ecological study. 
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6. Mesher D, Soldan K, Howell-Jones R, Panwar K, Manyenga P, Jit M, et al. Reduction in HPV 
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16/18 prevalence in sexually active young women following the introduction of HPV immunisation in 
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England. Vaccine. 2013;32(1):26-32.  
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7. Hariri S, Bennett NM, Niccolai LM, Schafer S, Park IU, Bloch KC, et al. Reduction in HPV 16/18- 
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associated high grade cervical lesions following HPV vaccine introduction in the United States - 2008- 
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8. Drolet M, Benard E, Boily MC, Ali H, Baandrup L, Bauer H, et al. Population-level impact and 
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Lancet Oncology. 2014;15(2):172-83. Epub 2014/01/18. 
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10. Duke P, Godwin M, Ratnam S, Dawson L, Fontaine D, Lear A, et al. Effect of vaginal selfsampling 
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11. Sancho-Garnier H, Tamalet C, Halfon P, Leandri FX, Le Retraite L, Djoufelkit K, et al. HPV 
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15. Catarino R, Jr., Vassilakos P, Stadali-Ullrich H, Royannez-Drevard I, Guillot C, Petignat P. 
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Annexes: Flowchart of the study. 
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Women attending health schools 
(18-31 years old, n=400)  
 
Baseline visit 
 Questionnaire 
 Self sample kit for HPV testing 
 Access to vaccination registries after 
signed consent 
 Self sample kit for HPV testing  
returned via mail 
 
 HPV analysis in the laboratory 
by Real time PCR 

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