Tableau d'honneur de la Faculté des études supérieures et postdoctorales, 2016-2017 / Introduction: En 2015, 65 pays avaient des programmes de vaccination contre les VPH. La modélisation mathématique a joué un rôle crucial dans leur implantation. Objectifs: Nous avons réalisé une revue systématique et analysé les prédictions de modèles mathématiques de l’efficacité populationnelle de la vaccination sur la prévalence des VPH-16/18/6/11 chez les femmes et les hommes, afin d’évaluer la robustesse/variabilité des prédictions concernant l’immunité de groupe, le bénéfice ajouté par la vaccination des garçons et l’élimination potentielle des VPH-16/18/6/11. Méthodes: Nous avons cherché dans Medline/Embase afin d’identifier les modèles dynamiques simulant l’impact populationnel de la vaccination sur les infections par les VPH-16/18/6/11 chez les femmes et les hommes. Les équipes participantes ont réalisé des prédictions pour 19 simulations standardisées. Nous avons calculé la réduction relative de la prévalence (RRprev) 70 ans après l’introduction de la vaccination. Les résultats présentés correspondent à la médiane(10ème; 90èmeperccentiles) des prédictions. Les cibles de la vaccination étaient les filles seulement ou les filles & garçons. Résultats: 16/19 équipes éligibles ont transmis leurs prédictions. Lorsque 40% des filles sont vaccinées, la RRprev du VPH-16 est 53%(46%; 68%) chez les femmes et 36%(28%; 61%) chez les hommes. Lorsque 80% des filles sont vaccinées, la RRprev est 93%(90%; 100%) chez les femmes et 83%(75%; 100%) chez les hommes. Vacciner aussi les garçons augmente la RRprev de 18%(13%; 32%) chez les femmes et 35%(27%; 39%) chez les hommes à 40% de couverture, et 7%(0%; 10%) et 16%(1%; 25%) à 80% de couverture. Les RRprev étaient plus élevées pour les VPH-18/6/11 (vs. VPH-16). Si 80% des filles & garçons sont vaccinés, les VPH-16/18/6/11 pourraient être éliminés. Interprétation: Même si les modèles diffèrent entre eux, les prédictions s’accordent sur: 1)immunité de groupe élevée même à basse couverture, 2)RRprev supérieures pour les VPH-18/6/11 (vs. VPH-16), 3)augmenter la couverture chez les filles a un meilleur impact qu’ajouter les garçons, 4)vacciner 80% des filles & garçons pourraient éliminer les VPH-16/18/6/11. / Background: As of 2015, 65 countries have introduced HPV vaccination programmes. Mathematical models have played a key role in the implementation of these programmes. Objectives: We conducted a systematic review and pooled-analysis of model predictions of population-level effectiveness of HPV vaccination against HPV-16/18/6/11 infection in women and men, to examine the robustness/variability of predicted populationnal effects, incremental benefit of vaccinating boys, and potential for HPV vaccine-type elimination. Methods: We searched Medline and Embase (2009-2015) for transmission-dynamic modeling studies predicting the population-level impact of vaccination on HPV-16/18/6/11 infections among women and men in high-income countries. Participating modeling teams produced predictions for 19 standardized scenarios. We derived pooled relative reduction in HPV prevalence (RRprev) 70 years after vaccination, using the median (10th; 90thpercentile) of model predictions. Strategies investigated were Girls-Only and Girls & Boys vaccination at 12 years of age. Findings: 16/19 eligible models, from ten high-income countries provided predictions. With 40% Girls-Only vaccination coverage, HPV-16 RRprev among women and men was 53%(46%; 68%) and 36%(28%; 61%), respectively. With 80% Girls-Only vaccination coverage, HPV-16 RRprev among women and men was 93%(90%; 100%) and 83%(75%; 100%), respectively. Vaccinating boys in addition to girls increased HPV-16 RRprev among women and men by 18%(13%; 32%) and 35%(27%; 39%) for 40% coverage, and 7%(0%; 10%) and 16%(1%; 25%) for 80% coverage, respectively. RRprev were greater for HPV-18/6/11 than HPV-16 for all scenarios. Finally at 80% coverage, most models predicted that Girls & Boys vaccination would eliminate HPV-16/18/6/11, with a median RRprev of 100% for women and men for all types. Interpretation: Although HPV models differ in structure, data used for calibration and setting, population-level predictions were generally concordant: 1) strong herd effects from vaccinating Girls-Only, even with low coverage, 2) greater post-vaccination reductions in HPV-18/6/11 infection (vs. HPV-16), 3) increasing coverage in girls provides greater impact than including boys, and 4) reaching 80% coverage in Girls would eliminate HPV-16/18/6/11, with a median RRprev of 100% for women and men for all types. Interpretation: Although HPV models differ in structure, data used for calibration and setting, population-level predictions were generally concordant: 1) strong herd effects from vaccinating Girls-Only, even with low coverage, 2) greater post-vaccination reductions in HPV-18/6/11 infection (vs. HPV-16), 3) increasing coverage in girls provides greater impact than including boys, and 4) reaching 80% coverage in Girls would eliminate HPV-16/18/6/11, with a median RRprev of 100% for women and men for all types. Interpretation: Although HPV models differ in structure, data used for calibration and setting, population-level predictions were generally concordant: 1) strong herd effects from vaccinating Girls-Only, even with low coverage, 2) greater post-vaccination reductions in HPV-18/6/11 infection (vs. HPV-16), 3) increasing coverage in girls provides greater impact than including boys, and 4) reaching 80% coverage in Girls & Boys could eliminate HPV-16/18/6/11.

Background: The HPV vaccine is a primary prevention method available to reduce the burden of HPV-related cancers and genital warts. The vaccine is currently approved for catch-up vaccination among women 18 to 26 years of age. Despite this recommendation, the rate of vaccine uptake among this group is considerably low (~34% uptake). One demographic characteristic that is consistently reported as a risk factor for non-vaccination is relationship status, specifically married or monogamous relationships. While the epidemiological data confirm this association, there is a lack of understanding how this risk factor operates. By elucidating the mechanism for this risk factor, HPV vaccine uptake among this consistently unvaccinated group could be improved. Purpose: The purpose of this study was to understand how young adult women’s relationship status influence informational needs, motivations, and behavioral skills related to HPV vaccination. This objective was achieved through the following specific aims: (1) assess how relationship status affects primary reasons for non-vaccination among 18 to 26 year old women; and (2) understand how relationship status frames HPV vaccine decision-making among 18 to 26 year old women. Methods: To effectively achieve these specific aims, a concurrent mixed-methods study design was conducted. In Phase I, a secondary data analysis using the 2010 National Health Interview Survey was employed to determine if women in relationships are less likely to be interested in vaccination and identify the primary reasons (e.g., misinformation, motivations, behavioral skills) for non-vaccination among different relationship status categories. In Phase II, in-depth interviews were conducted with a sample (N=50) of 18 to 26 year old women at the University of South Florida, stratified by relationship status and vaccination status. A comparative thematic analysis was conducted to determine if there were differences in informational needs, motivations, behavioral skills, and HPV vaccine decision-making between the groups. Results: Using NHIS 2010 data, women who were living with a partner (PR 1.44 95%CI 1.07-1.87) and never married (PR 1.41 95%CI 1.12-1.73) were less likely to be interested in HPV vaccination compared women who were married. Moreover, primary reasons for non-vaccination differed significantly by relationship status group (p Conclusion: This study found that relationship status impacts HPV vaccine decision-making among young adult women. Specifically, it operates by modifying risk perceptions for HPV, which serve as barriers to vaccination. Young adult women have the knowledge and behavioral skills necessary to access and understand the importance of HPV vaccination; however, women were unable to accurately perceive their risk for HPV, resulting in impaired motivation for vaccination. A potential approach to address this issue is the use of health literacy. Future research should integrate health literacy techniques with healthcare providers serving this population to assist in the evaluation process for risk of HPV. This will facilitate shared decision-making and patient-provider communication surrounding the HPV vaccine. This can ultimately promote HPV vaccination among young adult women and reduce the morbidity and mortality of HPV-related diseases.

Objectifs : Dans plusieurs pays la couverture vaccinale contre les virus du papillome humain (VPH) est associée aux déterminants sociaux des comportements sexuels et la participation au dépistage du cancer du col utérin. Ces vaccins protègent uniquement contre certains types de VPH, donc leur impact futur sur les VPH nonvaccinaux demeure incertain. L’hétérogénéité comportementale entre individus et biologique entre types de VPH affectera l’efficacité populationnelle de la vaccination contre les VPH. Les objectifs spécifiques de cette thèse étaient 1) de modéliser comment une couverture vaccinale inégale entre filles préadolescentes qui différeront selon leur activité sexuelle et leur participation au dépistage du cancer du col affectera l’efficacité populationnelle de la vaccination, 2) faire une synthèse et comparer les estimés d’efficacité croisée des vaccins contre les VPH dans des populations ADN-négatives aux VPH et 3) d’identifier, avec la modélisation, les devis d’étude épidémiologique qui réduisent les biais dans l’estimation des interactions biologiques entre types de VPH. Méthode : Nous avons utilisé des modèles de transmission dynamique et une revue systématique de la littérature pour répondre aux objectifs. 1) Nous avons modélisé une couverture vaccinale inégale entre filles qui différeront selon leur activité sexuelle et leur participation au dépistage, et examiné les changements postvaccination dans l’inégalité dans la prévalence des VPH et l’incidence des carcinomes malpighien (SCC) du col de l’utérus entre femmes ayant différents comportements. 2) Nous avons effectué une revue systématique et méta-analyse des efficacités croisées des vaccins contre les VPH estimées dans des populations ADNnégatives aux VPH. 3) Nous avons développé des modèles de transmission dynamique et d’interaction de deux types de VPH pour simuler les études épidémiologiques d’interactions entre les VPH. Résultats : Pour l’objectif 1), notre modèle de transmission prédit que l’efficacité populationnelle du vaccin dépendra de la distribution du vaccin dans la population. Après la vaccination, les inégalités absolues dans l’incidence de l’infection et des SCC entre groupes de femmes qui diffèrent selon leur activité sexuelle et leur participation au dépistage devraient diminuer. Inversement, les inégalités relatives pourraient augmenter si les femmes plus sexuellement actives et celles qui ne se font jamais dépister ont une couverture vaccinale moins élevée que les autres. Le taux d’incidence des SCC demeurera élevé chez les femmes qui ne sont jamais dépistées après la vaccination. L’efficacité croisée vaccinale et les interactions biologiques entre VPH ne sont pas encore assez bien caractérisées pour pouvoir prédire l’impact du vaccin sur les types de VPH nonvaccinaux. Pour l’objectif 2), notre méta-analyse des essais cliniques des vaccins suggère que le vaccin bivalent a une efficacité croisée significativement plus élevée que le quadrivalent contre les infections persistantes et lésions précancéreuses avec les VPH-31, 33 et 45. Les essais cliniques plus longs estiment une efficacité croisée plus faible. La modélisation des études épidémiologiques d’interactions pour l’objectif 3) montre que l’estimation des interactions biologiques entre types de VPH dans les études épidémiologiques est systématiquement biaisée par la corrélation entre le temps à risque d’infection avec un type de VPH et le temps à risque d’infection avec d’autres types de VPH. L’ajustement pour des marqueurs d’activité sexuelle ne réussit pas à contrôler ce biais. Une mesure valide des interactions biologiques entre types de VPH peut être obtenue uniquement avec des études épidémiologiques prospectives qui restreignent les analyses à des individus susceptibles ayant des partenaires sexuels infectés. Conclusion : L’hétérogénéité comportementale entre individus et l’hétérogénéité biologique entre VPH affecteront l’efficacité populationnelle du vaccin contre les VPH. Dans les contextes où les déterminants sociaux des comportements sexuels et la participation au dépistage sont aussi associés à la couverture vaccinale chez les préadolescentes, l’inégalité relative dans l’incidence des SCC risque d’augmenter. Ces comportements demeureront des facteurs de risque importants du cancer du col à l’avenir. L’effet à long terme du vaccin sur les types de VPH non-vaccinaux demeure incertain. Quoique nos résultats suggèrent que les vaccins offrent une efficacité croisée contre certains types de VPH, celle-ci pourrait diminuer après quelques années. Des interactions compétitives entre VPH pourraient exister malgré les associations observées entre les incidences des infections VPH, donc une augmentation post-vaccination de la prévalence des VPH non-vaccinaux demeure possible. Des devis d’analyse plus complexes sont nécessaires pour mesurer de façon valide les interactions biologiques entre les VPH dans les études épidémiologiques. / Objective: In many countries, uptake of the human papillomavirus (HPV) vaccine is associated with many of the same social determinants as cervical cancer and its behavioural risk factors, most notably sexual activity and screening participation. HPV vaccines only protect against a handful of oncogenic HPV types, so their impact on non-vaccine HPV types is uncertain. This behavioural heterogeneity between individuals and biological heterogeneity between HPV types will affect the population-level impact of HPV vaccination. The specific objectives were to 1) model how differential vaccine uptake between preadolescent girls who will have different sexual and cervical cancer screening behaviours can affect vaccination effectiveness, 2) review and compare estimates of HPV vaccine cross-efficacy in HPV-negative populations, and 3) use transmission modelling to identify the epidemiological study designs which reduce bias in the estimation of biological interactions between HPV types. Methods: We used transmission dynamic models and a systematic review of the literature to address these objectives. 1) We modeled different vaccine uptakes between preadolescent girls who will have different sexual and cervical cancer screening behaviours, and examined the predicted post-vaccination changes in inequalities in the prevalence of HPV and the incidence of cervical squamous cell carcinomas (SCC) between women with different behaviours. 2) We performed a systematic review and meta-analysis of HPV vaccine cross-efficacy in HPV-negative populations. 3) We developed dynamic transmission models of two HPV types to simulate epidemiological studies of biological interactions between HPV types. Results: For objective 1), our transmission dynamic model predicts that the population-level effectiveness of HPV vaccines will depend on its uptake distribution in the population. Absolute inequalities in the prevalence of infection and the incidence of SCC between women with different sexual and screening behaviours should diminish following vaccination. Inversely, relative inequalities between these women could increase if those who are more sexually active and who are never screened also have the lowest vaccine uptake. The incidence rate of SCC will remain high in women who are never screened post-vaccination. HPV vaccines’ cross-efficacy and the biological interactions between HPV types were not sufficiently quantified to allow predicting the impact of HPV vaccination on non-vaccine HPV types. For objective 2), our meta-analysis of vaccine clinical trials suggest that the bivalent vaccine has a significantly higher efficacy than the quadrivalent vaccine against infections and lesions with HPV-31, 33, and 45. Longer clinical trials estimate lower cross-efficacies. The simulation of epidemiological studies for objective 3) revealed that the estimation of biological interactions between HPV types in epidemiological studies is systematically biased by the correlation between the times at-risk for infection with different HPV types, which results in a cross-sectional and prospective correlation between their infection incidences. Adjusting for sexual behaviour markers does not control this bias. A valid measure of biological interactions between HPV types can only be obtained in prospective epidemiological studies which restrict analyses to times where individuals have an infected partner and thus are at-risk of infection. Conclusions: Behavioural heterogeneity between individuals and biological heterogeneity between HPV types will affect the population-level impact of HPV vaccination and should be considered in mathematical models and epidemiological studies. In contexts where the social determinants of sexual activity and screening are also associated with vaccine uptake in preadolescent girls, relative health inequalities may increase. These behaviours will remain important risk factors for cervical cancer in the vaccine era. The long-term effect of HPV vaccines on non-vaccine HPV types remains uncertain. While our results suggest that vaccines offer crossefficacy against certain HPV types, this cross-efficacy could wane within a few years. Competitive interactions between HPV types could exist despite observed associations between the incidences of different HPV type infections, so a post-vaccination increase in non-vaccine HPV types remains possible. More complex analysis designs are required to validly measure biological interactions between HPV types in epidemiological studies.

D’après la théorie de la compensation du risque, la vaccination contre les VPH pourrait entraîner une augmentation des comportements sexuels à risque. Cette étude visait à vérifier si une dose supplémentaire du vaccin Q-VPH administrée entre 13 et 15 ans est associée à la survenue des premiers rapports sexuels chez les filles vaccinées au Québec. L’analyse a été réalisée sur les données recueillies dans le cadre d’un essai randomisé en cours, ICIVPH. Après avoir toutes reçu deux doses de vaccin Q-HPV en quatrième année, seules les filles du groupe d’intervention ont reçu une troisième 60 mois après la première. Des filles sans expérience sexuelle à la randomisation et ayant répondu au questionnaire de suivi un an plus tard ont constitué notre sous-groupe d’étude. De 1581 filles, 798 (50,5 %) ont reçu une dose supplémentaire de vaccin Q-HPV et 783 (49,5 %) ne l’ont pas reçue (groupe témoin). À la randomisation, les deux groupes présentaient des caractéristiques similaires : âge moyen (14,8 ans), canadienne-française exclusive (70,5 %), naissance au Canada (91,3 %), utilisation de la contraception hormonale (12,0 %) et tabagisme (4,5 %). De même, un an après la randomisation, des proportions similaires de participantes ont débuté une activité sexuelle (17,2 % vs 19,9 % ; p 0,26), ont eu des rapports sexuels avec pénétration (14,9 % vs 16,4 % ; p 0,24) et ont utilisé le préservatif (67,5 % vs 63,4 % ; p 0,57). Deux participantes, une dans chaque groupe, ont signalé une ITS et une dans le groupe témoin a rapporté une grossesse. Dans l’analyse multivariée, l’initiation de l’activité sexuelle était associée à l’origine canadienne-française exclusive (RC 1,5 ; IC : 95 % : 1,1-2,0), au tabagisme (RC 3,0 ; IC : 95 % : 1,8-5,1) et à la contraception hormonale (RC 2,4 ; IC 95 % : 1,7-3,4). Nous n’avons pas observé une association entre le fait d’avoir reçu une dose supplémentaire de vaccin contre les VPH entre 13 et 15 ans et la survenue des premiers rapports sexuels et d’autres comportements sexuels à risque. / Some fear that HPV vaccination may lead to an increase in risky sexual behaviours, based on the theory of risk compensation. This study aimed to test whether receiving an additional dose of Q-HPV vaccine between the ages of 13 and 15, would lead to riskier sexual activity over a year, among teenage girls vaccinated in Quebec, Canada. We analyzed data collected as part of an ongoing randomized trial, ICI-VPH, investigating the role of a booster dose of HPV vaccine. All participants received 2 doses of Q-HPV vaccine in fourth grade. The intervention group received vaccine-booster dose 60 months after their first one. We analysed only girls who had no sexual experience at the time of the randomization and who responded to the follow-up questionnaire one year later. Of 1581 girls, 798 (50.5%) received an additional Q-HPV vaccine dose and 783 (49.5%) did not. At the time of randomization, groups showed similar characteristics: the mean age was 14.8 years, 70.5% self-identified as French-canadian only, 91.3% were born in Canada, 12.0% were using hormonal contraception and 4.5% were smokers. In the year following randomization, similar proportions of participants initiated sexual activity (17.2 % vs 19.9 %; p-value 0.26); initiated intercourse (14.9 % vs 16.4 %; pvalue 0.24); and used condoms (67.5 % versus 63.4 %; p-value 0.57). Only 2 participants reported an STI (one in each study group), and one reported a pregnancy (in the control group). In multivariate analysis, identifying as French- Canadian only (OR 1.5; 95 % CI: 1.1-2.0), tobacco smoking (OR 3.0; 95 % CI: 1.8-5.1) and hormonal contraception use (OR 2.4; 95 % CI: 1.7-3.4) were associated with sexual activity initiation. We did not observe an increase in risky sexual behaviors in adolescent girls who received an additional dose of HPV vaccine between 13 and 15 years of age.

Hispanic Americans experience a disparate burden of human papillomavirus vaccination (HPV)-related cancers. Despite vaccine availability, HPV vaccine uptake amid Hispanic American adolescent males in the United States is under the national goal. Furthermore, childhood vaccination compliance is driven by the parents; yet, there is little research on parents' perceptions of HPV vaccination of male children. The purpose of this phenomenological study was to explore the attitudes, beliefs, concerns, and decision- making factors of Hispanic American parents of male children aged 11- to 13- years-old surrounding HPV vaccination. The health belief model provided the framework for the study. Face-to-face interviews were conducted with 12 participants in a rural county in Colorado in which Hispanic Americans had a higher rate of reportable sexually transmitted infections than non-Hispanics. Data analysis included descriptive coding to summarize and synthesize the interview results. The results showed Hispanic parents had a positive attitude toward HPV vaccination, and parents believed that the vaccination would protect their child. Most of the parents were aware of the HPV vaccine. The parents believed in healthcare providers and would accept the vaccine if it was recommended by them. Despite several parents having concerns about HPV vaccinations, they still claimed they would vaccinate their child. The findings from the study can be used to inform educational offerings regarding HPV vaccination for Hispanic American boys.

Knowledge and attitudes to HPV immunisation IV Author: Tereza Jelínková Thesis supervisor: PharmDr. Eva Zimčíková, Ph.D. Introduction HPV infection is one of the most common sexually transmitted diseases causing, apart from genital warts, other malignancies, most often cervical cancer. The most effective way of prevention is vaccination. So far, there have been 3 types of vaccines, most recent one being the nonavalent vaccine providing up to 90 % protection against cervical cancer- causing HPV, in contrast to the previously available 70 % protection from bivalent or quadrivalent vaccines. Aims The main aim of this thesis was to investigate the knowledge and attitudes towards vaccination against HPV, and knowledge about HPV in general, among secondary school students. Furthermore, to determine their vaccination status and compare the findings with data from previous theses, including a comparison of their knowledge about HPV and relevant prevention. Methodology The data was obtained by means of a questionnaire survey, which took place at three secondary schools. In December 2017 at Gymnázium in Mladá Boleslav, then during June 2018 at Gymnázium in Brandýs nad Labem, and finally in September 2018 at Gymnázium Chotěboř. The obtained data was recorded in a Microsoft Excel spreadsheet and then...

In the United States, parents' health beliefs affect HPV vaccination decisions for children. Our team acquired insights into mothers' health beliefs from their reactions and comments to posts on HPV vaccination in a social media adolescent health campaign in a randomized trial (n = 881 mothers; 63.1% reported daughters had 1+ doses of the HPV vaccine) evaluating communication intended to reduce daughters' indoor tanning. A total of 10 HPV vaccination messages in didactic (n = 7) and narrative (n = 3) formats were posted on vaccination need, uptake, and effectiveness and stories of young women who died from cervical cancer and a mother's decision to vaccinate her daughters. These posts received 28 reactions (like, love, and sad buttons; mean = 2.8 per post) and 80 comments (mean = 8.0 per post). More comments were favorable (n = 43) than unfavorable (n = 34). Data was not collected on views for posts. The most common favorable comment reported that daughters were vaccinated (n = 31). Unfavorable comments cited safety concerns, lack of physician support, distrust of pro-vaccine sources, and increased sexual activity of daughters. Mothers posting unfavorable (18.2%) as opposed to favorable (78.6%) comments or not commenting (64.0%) were less likely to have had their daughters vaccinated (chi-square = 22.27, p < 0.001). Favorable comments often did not state reasons for vaccinating. Concerns about lack of vaccine safety remain a barrier. Mothers may express distrust in pro-vaccine sources to reduce discomfort with not vaccinating daughters to reduce their risk for HPV infection. Many mothers who remained silent had vaccinated daughters, which suggests they did not resisit HPV vaccination.

Objectif: Les deux objectifs principaux de cette thèse étaient de développer 1) des modèles mathématiques pour prédire l’efficacité populationnelle de la vaccination contre les VPH et 2) des méthodes pour quantifier l’incertitude autour des prédictions de ces modèles. Méthode: Nous avons développé trois modèles mathématiques: 1) un modèle statique compartimental de l’histoire naturelle du cancer du col de l’utérus (Modèle1), 2) un modèle dynamique individus-centré de l’infection aux VPH (Modèle2), et 3) un modèle dynamique individus-centré de l’histoire naturelle des maladies associées aux VPH (Modèle3). Résultats: Les trois modèles ont prédit que la vaccination des filles pourrait diminuer substantiellement le fardeau des maladies associées aux VPH, au Canada. La durée de protection vaccinale a été identifiée comme étant le paramètre influençant le plus les résultats d’efficacité populationnelle. Le modèle 3 a prédit que le vaccin bivalent pourrait prévenir légèrement plus de cas de cancer du col sur le long terme, alors que le vaccin quadrivalent a le potentiel de réduire drastiquement les condylomes sur le court terme. Finalement, le modèle 3 a suggéré que le vaccin nonavalent actuellement en développement pourrait rapporter des bénéfices additionnels importants si son efficacité et sa durée de protection sont supérieures à 85% et 30 ans, respectivement. D’un point de vue méthodologique, nous avons développé une procédure de calibration multivariée capable de quantifier l’incertitude paramétrique dans les modèles. Elle nous a permis de montrer l’importance de cette incertitude et la nécessité de la représenter dans les résultats. Pour finir, nous avons quantifié l’incertitude structurelle liée aux hypothèses de modélisation suivantes: immunité de groupe, immunité naturelle, durée des partenariats, groupement des génotypes VPH et fonctions de temps utilisées pour représenter le déclin de la protection vaccinale. Conclusion: Nous avons développé des modèles de complexité croissante, en parallèle avec les méthodes de calibration adéquates, afin de pouvoir suivre et répondre aux questions de santé publique du moment. Notre dernier modèle est présentement utilisé pour examiner l’impact de la vaccination sur les inégalités de santé et sera utilisé dans le futur pour évaluer le rapport de coût-efficacité des nouveaux vaccins et optimiser les programmes de dépistage. / Objective: The two main objectives of this thesis were to develop 1) mathematical models to predict the population-level impact of HPV vaccination in Canada, and 2) methods to quantify uncertainty around model predictions. Methods: We developed three mathematical models: 1) a static compartmental model of cervical cancer natural history (Model 1), 2) an individual-based dynamic model of HPV infection (Model 2), and 3) the first individual-based transmission-dynamic model of partnership formation and dissolution, and natural history of multi-type HPV infection and disease (anogenital warts, and cervical, anogenital and oropharyngeal cancers) (Model 3). For each model, an extensive fitting procedure was conducted, which identified multiple posterior parameter combinations (out of hundreds of thousands of prior parameter sets) that fit simultaneously highly stratified behavioral and epidemiologic data, taken from the literature, population-based datasets, and original studies. Parameter uncertainty was illustrated by presenting the median [10th; 90th percentiles] of predictions, using the posterior parameter combinations. Sensitivity analysis was conducted varying vaccine efficacy, duration of protection, coverage and vaccination strategies. Results: We provided the following evidence for HPV vaccination recommendations. Models 1-3 predicted that girls-only HPV vaccination can substantially reduce HPV-related burden of disease. Predictions were most sensitive to duration of vaccine protection. Model 3 predicted that the bivalent vaccine will be slightly more effective at preventing cervical cancer in the longer term. However, the quadrivalent vaccine will substantially reduce anogenital warts. Finally, the candidate nonavalent vaccine has the potential to produce substantial incremental benefits if its efficacy and duration of protection are at least 85% and 30 years, respectively. From a methodological point of view, we illustrated that parameter uncertainty surrounding HPV natural history parameters is important and must be presented when providing predictions to decision makers. Finally, we identified key structural assumptions that influence predictions: herd immunity, natural immunity, partnership duration, individual genotypes and vaccine waning function. Conclusion: We developed increasingly sophisticated HPV models and calibration techniques to keep track with the increasingly complex policy questions being asked. Our final model is being used to examine the impact of HPV vaccination on health inequalities, evaluate the cost-effectiveness of HPV vaccination, and optimize screening.

Cervical cancer is the second most common cancer that women suffer from worldwide. Every year more than 270,000 women die from cervical cancer, and it is one of the top ten cancer that Taiwanese women suffer from. Differ from other kinds of cancer, cervical cancer can be effectively prevented by vaccination, since most cervical cancers are caused by HPV(Human Papillomavirus) infection. HPV infection is most common in people in their late teens and early 20s, and the HPV vaccine targets the HPV types that most commonly cause cervical cancer and can cause some other cancers. It also protects against the HPV types that cause most genital warts. The HPV vaccine is highly effective in preventing the targeted HPV types, as well as the most common health problems caused by them. Though HPV vaccination is included in the national immunization program in some countries, the vaccines are not provided to every female at no cost in Taiwan. While some cities and counties provides HPV vaccine for every female or a certain group of female gratuitously, female citizens of other cities and counties would have to pay approximately $300-360 USD for vaccination. This inconsistent policy among Taiwan has been questioned by local congressmen and citizens. To re-examine the HPV vaccine policy and implementation procedure among each local government in Taiwan, the Health Promotion Administration, Ministry of Health and Welfare (HPA) as well as ten local governments with different HPV vaccination policies were interviewed and evaluated. The research concludes that with no united HPV vaccination policy, the goals of the policy among the local governments is different, some even undefined, the implementation levels of each local government is uneven, and misleading communication between the central and the local governments exist. A united policy with specific goal, implementation guidelines, report system, two-way communication system should and would make the vaccination policy more ample, and equal.