Deterministic modeling for transmission of Human Papillomavirus 6/11: impact of vaccination.

International audienceThis paper is devoted to assess the impact of quadrivalent Human Papillomavirus (HPV) vaccine on prevalence of non-oncogenic HPV 6/11 types in French males and females. For this purpose, a non-linear dynamic model of heterosexual transmission for HPV 6/11 types infection is developed, which accounts for immunity due to vaccination in particular. The vaccinated reproduction number Rv is derived using the approach described by Diekmann (2010) called the Next Generation Operator approach. The model proposed is analyzed, with regard to existence and uniqueness of the solution, steady-state stability. Precisely, the stability of the model is investigated depending on the sign of Rv − 1. Prevalence data are used to fit a numerical HPV model, so as to assess infection rates. Our approach suggests that 10 years after introducting vaccination, the prevalence of HPV 6/11 types in females will be halved and that in males will be reduced by one quarter, assuming a sustained vaccine coverage of 30% among females. Using the formula we derived for the vaccinated reproduction number, we show that the non-oncogenic HPV 6/11 types would be eradicated if vaccine coverage in females is kept above 12%. Human Papillomavirus, deterministic epidemic model, equilibrium, stability, reproduction number, vaccination

Increased risk of contralateral breast cancers among overweight and obese women: a time-dependent association

Abstract Breast cancer (BC) survivors are at increased risk of second cancers. Obesity is commonly recognized as a risk factor of BC in postmenopausal period and a prognosis factor in BC regardless of menopausal status. Our aim was to study whether overweight BC survivors were at increased risk of contralateral BC (CBC). Our population was a large cohort of women followed since a first BC without distant spread and/or synchronous CBC. Body mass index (BMI) was assessed at diagnosis time. Binary codings of BMI were used to oppose overweight and obese patients to the others. Survival analyses were used including Cox models. Assumed hypothesis of proportional hazards was explored using graphical methods, Schoenfeld residuals and time-dependant covariates. In case of nonproportional hazards, survival models were computed over time periods. Over 15,000 patients were included in our study. Incidence of CBC was 8. 8 (8.3-9.3)/1000 personyears and increased during follow-up. A significant timedependent association between overweight and CBC was observed. After 10 years of follow-up, we found a significant increased hazard of CBC among patients with a BMI above 25 kg/m 2 : the adjusted hazard ratio was 1.50(1.21-1.86), P = 0.001. After 10 years of follow-up, our study found a poorer prognosis among overweight BC survivors regarding CBC events. While benefits from diet habits and weight control may be expected during the long-term follow-up, they have yet to be established using randomized clinical trials. Keywords Contralateral breast cancer Á Non-proportional hazards Body mass index Á Overweight Á Time-dependent covariate Á Breast cancer prognosis Abbreviations BC Breast cancer BMI Body mass index CBC Contralateral breast cancer HR Hazard rati

Le surpoids un facteur de risque de cancers du sein controlatéraux à long terme

International audienceIntroduction.- La corpulence représente un facteur de mauvais pronostique dans le cancer du sein. Cependant, l'association entre corpulence et récidive controlatérale d'un cancer du sein reste peu étudiée. L'obésité représente un facteur de risque pour les cancers du sein post ménopausiques. Nous nous proposons d'étudier l'association entre la corpulence et la récidive controlatérale du cancer du sein. Méthodes.- Nous avons constitué une cohorte de femmes atteintes d'un premier cancer du sein non métastatique d'emblée. La corpulence était mesurée au moment du diagnostic à l'aide de l'indice de masse corporelle opposant les patientes corpulentes (en surpoids ou obèses) aux autres. Des analyses de survie ont été menées tout en vérifiant l'hypothèse des risques proportionnels. Résultats.- La population étudiée était constituée de plus de 15 000 femmes dont l'âge moyen était de 54 ans. Le délai médian de suivi était de 10 ans, le recul maximal était de 24 ans. Il existait une augmentation significative des cancers du sein controlatéraux parmi les femmes ayant un indice de masse corporelle audelà de 25 kg/m2. Cette association était dépendante du temps : l'augmentation des récidives controlatérales parmi les femmes corpulentes était significative seulement à partir de la dixième année de suivi. Entre 10 et 24 ans de suivi, l'hypothèse des risques proportionnels était vérifiée. Le risque relatif ajusté sur les facteurs de risques communément admis pour le cancer du sein controlatéral était de 1,50 (1,21-1,86), p = 0,001. Discussion/Conclusion.- Les femmes corpulentes ont une augmentation du risque de second cancer du sein à long terme. Dans un contexte de progression du surpoids, de la prévalence et de l'incidence du cancer du sein, cette problématique ne peut que concerner de plus en plus de femmes. Les interventions diététiques, l'exercice physique régulier et le contrôle du poids peuvent être privilégiés pour améliorer le pronostic des femmes à risque

Modélisation déterministe de la transmission des infections à Papillomavirus Humain: effets de la vaccination

International audienceLes infections à Papillomavirus Humain sont incriminées dans la quasi-totalité des cancers du col de l'utérus chez la femme. En France, 3400 nouveaux cas de cancer du col utérin et 1000 décès par cancer du col ont été estimés pour l'année 2000. Depuis la mise sur le marché récente de deux vaccins, une réduction de l'incidence de ces infections et des cancers du col de l'utérus est attendue. L'utilisation de modèles mathématiques permet de comparer différentes stratégies vaccinales et de retenir celles qui ont un rapport coût/efficacité optimal. Nous avons développé un modèle dynamique de transmission hétérosexuelle des infections à Papillomavirus Humain pour les sérotypes 6/11/16/18 qui sont couverts par le vaccin quadrivalent. Un modèle déterministe de type Susceptible-Infecté-Susceptible a été utilisé avec stratification selon le genre et le sérotype. L'immunité procurée par la vaccination est prise en compte. La sensibilité des prédictions du modèle a été évaluée par rapport à l'incertitude des paramètres. Trois scénarios de vaccination ont été comparés en considérant les prévalences des infections à Papillomavirus obtenues. L'analyse de sensibilité a mis en évidence l'importance de l'imprécision des durées d'infection des différents sérotypes d'infection à HPV sur les prédictions du modèle. La modélisation de la transmission des infections à HPV a permis de comparer l'efficacité potentielle de 3 scénarios de vaccination. La vaccination de la moitié des hommes entrant chaque année dans la population sexuellement active donne les mêmes résultats qu'une large couverture vaccinale (90%) des femmes entrant dans la population sexuellement active. Nos résultats montrent que l'introduction de la vaccination des jeunes garçons peut être motivée par une faible couverture vaccinale atteinte pour les jeunes femmes

Efficacy of Vaccination against HPV Infections to Prevent Cervical Cancer in France: Present Assessment and Pathways to Improve Vaccination Policies

Background: Seventy percent of sexually active individuals will be infected with Human Papillomavirus (HPV) during their lifetime. These infections are incriminated for almost all cervical cancers. In France, 3,068 new cases of cervical cancer and 1,067 deaths from cervical cancer occurred in 2005. Two vaccines against HPV infections are currently available and vaccination policies aim to decrease the incidence of HPV infections and of cervical cancers. In France, vaccine coverage has been reported to be low. Methods: We developed a dynamic model for the heterosexual transmission of Human Papillomavirus types 16 and 18, which are covered by available vaccines. A deterministic model was used with stratification on gender, age and sexual behavior. Immunity obtained from vaccination was taken into account. The model was calibrated using French data of cervical cancer incidence. Results: In view of current vaccine coverage and screening, we expected a 32 % and 83 % reduction in the incidence of cervical cancers due to HPV 16/18, after 20 years and 50 years of vaccine introduction respectively. Vaccine coverage and screening rates were assumed to be constant. However, increasing vaccine coverage in women or vaccinating girls before 14 showed a better impact on cervical cancer incidence. On the other hand, performing vaccination in men improves the effect on cervical cancer incidence only moderately, compared to strategies in females only

Increased risk of contralateral breast cancers among overweight and obese women: a time-dependent association.

International audienceBreast cancer (BC) survivors are at increased risk of second cancers. Obesity is commonly recognized as a risk factor of BC in postmenopausal period and a prognosis factor in BC regardless of menopausal status. Our aim was to study whether overweight BC survivors were at increased risk of contralateral BC (CBC). Our population was a large cohort of women followed since a first BC without distant spread and/or synchronous CBC. Body mass index (BMI) was assessed at diagnosis time. Binary codings of BMI were used to oppose overweight and obese patients to the others. Survival analyses were used including Cox models. Assumed hypothesis of proportional hazards was explored using graphical methods, Schoenfeld residuals and time-dependant covariates. In case of non-proportional hazards, survival models were computed over time periods. Over 15,000 patients were included in our study. Incidence of CBC was 8.8 (8.3-9.3)/1000 person-years and increased during follow-up. A significant time-dependent association between overweight and CBC was observed. After 10 years of follow-up, we found a significant increased hazard of CBC among patients with a BMI above 25 kg/m(2): the adjusted hazard ratio was 1.50(1.21-1.86), P = 0.001. After 10 years of follow-up, our study found a poorer prognosis among overweight BC survivors regarding CBC events. While benefits from diet habits and weight control may be expected during the long-term follow-up, they have yet to be established using randomized clinical trials

Expected Diminution of number of deaths (per year) due to cervical cancer after introduction of vaccine compared to number of deaths without vaccine.

<p>Expected Diminution of number of deaths (per year) due to cervical cancer after introduction of vaccine compared to number of deaths without vaccine.</p

Flow diagram in non-vaccinated population.

<p>For one age-group <i>j</i> (j = 1…14) and one group of sexual behavior <i>l</i> (l = 1…4): Black solid arrows represent infection or progression of the disease; black dotted arrows represent clearance of infection or regression of the disease; gray dotted arrows represent exit of the model (due to death or age >84); bold arrows represent specific mortality due to cervical cancer.</p

Prevalence of HPV 16/18 for women in each scenario 10, 20 and 50 years after initiation of vaccination (t = 0).

<p>Vaccine coverage was supposed constant in each scenario. In parentheses, % of reduction in HPV prevalence compared to the case without vaccination.</p