Amy Leval

Quadrivalent Human Papillomavirus Vaccine Effectiveness: A Swedish National Cohort Study

Background Incidence of condyloma, or genital warts (GW), is the earliest possible disease outcome to measure when assessing the effectiveness of human papillomavirus (HPV) vaccination strategies. Efficacy trials that follow prespecified inclusion and exclusion criteria may not be fully generalizable to real-life HPV vaccination programs, which target a broader segment of the population. We assessed GW incidence after on-demand vaccination with quadrivalent HPV vaccine using individual-level data from the entire Swedish population. Methods An open cohort of girls and women aged 10 to 44 years living in Sweden between 2006 and 2010 (N > 2.2 million) was linked to multiple population registers to identify incident GW in relation to HPV vaccination. For vaccine effectiveness, incidence rate ratios of GW were estimated using time-to-event analyses with adjustment for attained age and parental education level, stratifying on age at first vaccination. Results A total of 124 000 girls and women were vaccinated between 2006 and 2010. Girls and women with at least one university-educated parent were 15 times more likely to be vaccinated before age 20 years than girls and women whose parents did not complete high school (relative risk ratio = 15.45, 95% confidence interval [CI] = 14.65 to 16.30). Among those aged older than 20 years, GW rates declined among the unvaccinated, suggesting that HPV vaccines were preferentially used by women at high risk of GW. Vaccination effectiveness was 76% (95% CI = 73% to 79%) among those who received three doses of the vaccine with their first dose before age 20 years. Vaccine effectiveness was highest in girls vaccinated before age 14 years (effectiveness = 93%, 95% CI = 73% to 98%). Conclusions Young age at first vaccination is imperative for maximizing quadrivalent HPV vaccine effectiveness.

Incidence of Genital Warts in Sweden Before and After Quadrivalent Human Papillomavirus Vaccine Availability

BACKGROUND More than 90% of genital warts (GW) cases are caused by human papillomavirus (HPV) types 6 and 11. The introduction of HPV vaccines necessitates the estimation of the population-based incidence of GW immediately before and after vaccination uptake. METHODS Incidence proportions were calculated using the entire population aged 10–44 years living in Sweden during 2006–2010. The Prescribed Drug Register and the National Patient Register were used to define GW episodes. Time trends were estimated using Poisson regression. RESULTS In 2010, age-stratified incidence proportions of GW were highest for 20-year-old women (956 cases/100 000), while the incidence proportion among males was greatest at the slightly older age of 24 years (1137 cases/100 000). Crude rates were marginally higher among males than among females during 2006–2007 and appeared to later diverge. Between 2008 and 2010, the overall incidence appeared to increase among males, and the incidence among females declined. Females aged 17 and 18 years had a >25% decline in GW rates between 2006 and 2010, with significant decreases through the age of 25 years. CONCLUSIONS This study provides a reasonable estimation of the incidence of GW in the Swedish population by use of register data, with results comparable to those from previous smaller studies. There was a downward trend of GW incidence among younger females between 2006 and 2010.

Association of Varying Number of Doses of Quadrivalent Human Papillomavirus Vaccine With Incidence of Condyloma

IMPORTANCE Determining vaccine dose-level protection is essential to minimize program costs and increase mass vaccination program feasibility. Currently, a 3-dose vaccination schedule is recommended for both the quadrivalent and bivalent human papillomavirus (HPV) vaccines. Although the primary goal of HPV vaccination programs is to prevent cervical cancer, condyloma related to HPV types 6 and 11 is also prevented with the quadrivalent vaccine and represents the earliest measurable preventable disease outcome for the HPV vaccine. OBJECTIVE To examine the association between quadrivalent HPV vaccination and first occurrence of condyloma in relation to vaccine dose in a population-based setting. DESIGN, SETTING, AND PARTICIPANTS An open cohort of all females aged 10 to 24 years living in Sweden (n = 1,045,165) was followed up between 2006 and 2010 for HPV vaccination and first occurrence of condyloma using the Swedish nationwide population-based health data registers. MAIN OUTCOMES AND MEASURES Incidence rate ratios (IRRs) and incidence rate differences (IRDs) of condyloma were estimated using Poisson regression with vaccine dose as a time-dependent exposure, adjusting for attained age and parental education, and stratified on age at first vaccination. To account for prevalent infections, models included a buffer period of delayed case counting. RESULTS A total of 20,383 incident cases of condyloma were identified during follow-up, including 322 cases after receipt of at least 1 dose of the vaccine. For individuals aged 10 to 16 years at first vaccination, receipt of 3 doses was associated with an IRR of 0.18 (95% CI, 0.15-0.22) for condyloma, whereas receipt of 2 doses was associated with an IRR of 0.29 (95% CI, 0.21-0.40). One dose was associated with an IRR of 0.31 (95% CI, 0.20-0.49), which corresponds to an IRD of 384 cases (95% CI, 305-464) per 100,000 person-years, compared with no vaccination. The corresponding IRDs for 2 doses were 400 cases (95% CI, 346-454) and for 3 doses, 459 cases (95% CI, 437-482). The number of prevented cases between 3 and 2 doses was 59 (95% CI, 2-117) per 100,000 person-years. CONCLUSIONS AND RELEVANCE Although maximum reduction in condyloma risk was seen after receipt of 3 doses of quadrivalent HPV vaccine, receipt of 2 vaccine doses was also associated with a considerable reduction in condyloma risk. The implications of these findings for the relationship between number of vaccine doses and cervical cancer risk require further investigation.

Assessing Perceived Risk and STI Prevention Behavior: A National Population-Based Study with Special Reference to HPV

Introduction To better understand trends in sexually transmitted infection (STI) prevention, specifically low prevalence of condom use with temporary partners, the aim of this study was to examine factors associated with condom use and perceptions of STI risk amongst individuals at risk, with the underlying assumption that STI risk perceptions and STI prevention behaviors are correlated. Methods A national population-based survey on human papillomavirus (HPV) and sexual habits of young adults aged 18–30 was conducted in Sweden in 2007, with 1712 men and 8855 women participating. Regression analyses stratified by gender were performed to measure condom use with temporary partners and STI risk perception. Results Mens condom use was not associated with STI risk perception while womens was. Awareness of and disease severity perceptions were not associated with either condom use or risk perception though education level correlated with condom use. Womens young age at sexual debut was associated with a higher risk of non-condom use later in life (OR 1.95 95% CI: 1.46–2.60). Women with immigrant mothers were less likely to report seldom/never use of condoms with temporary partners compared to women with Swedish-born mothers (OR 0.53 95% CI: 0.37–0.77). Correlates to STI risk perception differ substantially between sexes. Number of reported temporary partners was the only factor associated for both men and women with condom use and STI risk perception. Conclusions Public health interventions advocating condom use with new partners could consider employing tactics besides those which primarily aim to increase knowledge or self-perceived risk if they are to be more effective in STI reduction. Gender-specific prevention strategies could be effective considering the differences found in this study.

How can young women be encouraged to attend cervical cancer screening? : Suggestions from face-to-face and internet focus group discussions with 30 year-old women in Stockholm, Sweden

Abstract Background. Cervical cancer screening (CCS) using Pap-smears has been carried out for decades and is still an essential tool for secondary cancer prevention. Focus has traditionally been on what hinders womens attendance, instead of researching this issue from a positive standpoint, i.e. what factors encourage women to take a Pap-smear? In this article, we therefore explore issues that 30-year-old women have addressed as encouraging CCS attendance, with particular focus on aspects susceptible to intervention. Material and methods. Through the population-based cervical cancer screening (PCCSP) registry in Stockholm, Sweden, a stratified random sampling technique was used to recruit women from the same birth cohort with varied CCS histories and results. Nine face-to-face focus groups discussions (FGDs) and 30 internet-based FGDs were conducted with a total of 138 women aged 30. Qualitative analysis was inspired by interpretative description, to generate clinically relevant and useful data. Results. In general, these women expressed positive views about the PCCSP as an existing service, regardless of screening history. They described a wide range of factors encompassing the entire screening trajectory from invitation through follow-up which could motivate young women to CCS participation, including social marketing. Many of the suggestions related to individualization of the PCCSP, as well as a need to understand the relationship between human papilloma virus (HPV) and cervical cancer. Discusssion. These results are discussed in terms of the inherent tension between population-based public health initiatives and individually-oriented health care provision. Many suggestions given are already incorporated into the existing Stockholm-Gotland screening program, although this information may not reach women who need it. New research should test whether systematic information on HPV may provide a missing link in motivating young women to attend CCS, and which of their suggestions can serve to increase CCS participation.

Obstetric care at the intersection of science and culture: Swedish doctors' perspectives on obstetric care of women who have undergone female genital cutting.

Providing healthcare for women having undergone female genital cutting can present challenges. The women might require special obstetric care, including an anterior episiotomy (defibulation) for infibulated women. This paper explores how Swedish doctors caring for these women describe, explain and reason about their care and relevant policies in a Swedish context. A qualitative study was carried out with 13 chief/senior obstetricians and seven senior house officers. There was little consensus among the interviewed doctors on what constitutes good obstetric care for women with FGC or how care should be provided. Major problems include: inconsistent policy and praxis; uncoordinated care trajectories; diffuse professional role responsibilities; difficulties in monitoring labour and fetal status; and inhibited communication. The data highlight the need for increased awareness and reflective praxis both on the part of individual practitioners, and on an organisational level, which takes account of the special needs of different users.

Tick borne encephalitis (TBE)-vaccination coverage and analysis of variables associated with vaccination, Sweden

To estimate the tick borne encephalitis (TBE)-vaccination coverage in the greater Stockholm region, we sent a questionnaire to a randomized sample of 8000 individuals in 2013. Fifty-three percent of all respondents (n=4307) reported being vaccinated against TBE at least once. Reasons for not vaccinating included: no perceived risk (28.6%), too expensive (25.6%), did not have the time or opportunity (23%) and worried about vaccine side-effects (20.5%). Multiple logistic regression revealed that the probability of being vaccinated was higher among those who reported ≥2 weeks outdoor exposure in a known high risk area (OR 4.13 95% CI 3.54-4.81) and in individuals ≥60 years of age compared to all other age groups (OR 0.67 95% CI 0.55-0.81). A high net household income was associated with a higher probability of being vaccinated (OR 2.10 95% CI 1.6-2.73). Being born outside Europe was negatively correlated (OR 0.57 95% CI 0.39-0.83). Based on our findings the estimated TBE-incidence in the unvaccinated regional population was 8.5-12/100,000 which is comparable with high endemic areas as the Baltic region and Central Europe. We suggest targeted vaccination and reimbursement strategies in high-endemic areas of Sweden. Our results indicate a need for improved public information about TBE.

Cost of Preventing, Managing, and Treating Human Papillomavirus (HPV)-Related Diseases in Sweden before the Introduction of Quadrivalent HPV Vaccination

Objective Costs associated with HPV-related diseases such as cervical dysplasia, cervical cancer, and genital warts have not been evaluated in Sweden. These costs must be estimated in order to determine the potential savings if these diseases were eradicated and to assess the combined cost-effectiveness of HPV vaccination and cervical cancer screening. The present study aimed to estimate prevention, management, and treatment costs associated with cervical dysplasia, cervical cancer, and genital warts from a societal perspective in Sweden in 2009, 1 year before the quadrivalent HPV vaccination program was implemented. Methods and Materials Data from the Swedish cervical cancer screening program was used to calculate the costs associated with prevention (cytological cervical cancer screening), management (colposcopy and biopsy following inadequate/abnormal cytological results), and treatment of CIN. Swedish official statistics were used to estimate treatment costs associated with cervical cancer. Published epidemiological data were used to estimate the number of incident, recurrent, and persistent cases of genital warts; a clinical expert panel assessed management and treatment procedures. Estimated visits, procedures, and use of medications were used to calculate the annual cost associated with genital warts. Results From a societal perspective, total estimated costs associated with cervical cancer and genital warts in 2009 were €106.6 million, of which €81.4 million (76%) were direct medical costs. Costs associated with prevention, management, and treatment of CIN were €74 million; screening and management costs for women with normal and inadequate cytology alone accounted for 76% of this sum. The treatment costs associated with incident and prevalent cervical cancer and palliative care were €23 million. Estimated costs for incident, recurrent and persistent cases of genital warts were €9.8 million. Conclusion Prevention, management, and treatment costs associated with cervical dysplasia, cervical cancer, and genital warts are substantial. Defining these costs is important for future cost-effectiveness analyses of the quadrivalent HPV vaccination program in Sweden.

Real-time real-world analysis of seasonal influenza vaccine effectiveness: method development and assessment of a population-based cohort in Stockholm County, Sweden, seasons 2011/12 to 2014/15.

Real-world estimates of seasonal influenza vaccine effectiveness (VE) are important for early detection of vaccine failure. We developed a method for evaluating real-time in-season vaccine effectiveness (IVE) and overall seasonal VE. In a retrospective, register-based, cohort study including all two million individuals in Stockholm County, Sweden, during the influenza seasons from 2011/12 to 2014/15, vaccination status was obtained from Stockholm’s vaccine register. Main outcomes were hospitalisation or primary care visits for influenza (International Classification of Disease (ICD)-10 codes J09-J11). VE was assessed using Cox multivariate stratified and non-stratified analyses adjusting for age, sex, socioeconomic status, comorbidities and previous influenza vaccinations. Stratified analyses showed moderate VE in prevention of influenza hospitalisations among chronically ill adults ≥ 65 years in two of four seasons, and lower but still significant VE in one season; 53% (95% confidence interval (CI): 33–67) in 2012/13, 55% (95% CI: 25–73) in 2013/14 and 18% (95% CI: 3–31) in 2014/15. In conclusion, seasonal influenza vaccination was associated with substantial reductions in influenza-specific hospitalisation, particularly in adults ≥ 65 years with underlying chronic conditions. With the use of population-based patient register data on influenza-specific outcomes it will be possible to obtain real-time estimates of seasonal influenza VE.

HIV drug therapy duration; a Swedish real world nationwide cohort study on InfCareHIV 2009-2014.

Background As HIV infection needs a lifelong treatment, studying drug therapy duration and factors influencing treatment durability is crucial. The Swedish database InfCareHIV includes high quality data from more than 99% of all patients diagnosed with HIV infection in Sweden and provides a unique opportunity to examine outcomes in a nationwide real world cohort. Methods Adult patients who started a new therapy defined as a new 3rd agent (all antiretrovirals that are not N[t]RTIs) 2009–2014 with more than 100 observations in treatment-naive or treatment-experienced patients were included. Dolutegravir was excluded due to short follow up period. Multivariate Cox proportional hazards models were used to estimate hazard ratios for treatment discontinuation. Results In treatment-naïve 2541 patients started 2583 episodes of treatments with a 3rd agent. Efavirenz was most commonly used (n = 1096) followed by darunavir (n = 504), atazanavir (n = 386), lopinavir (n = 292), rilpivirine (n = 156) and raltegravir (n = 149). In comparison with efavirenz, patients on rilpivirine were least likely to discontinue treatment (adjusted HR 0.33; 95% CI 0.20–0.54, p<0.001), while patients on lopinavir were most likely to discontinue treatment (adjusted HR 2.80; 95% CI 2.30–3.40, p<0.001). Also raltegravir was associated with early treatment discontinuation (adjusted HR 1.47; 95% CI 1.12–1.92, p = 0.005). The adjusted HR for atazanavir and darunavir were not significantly different from efavirenz. In treatment-experienced 2991 patients started 4552 episodes of treatments with a 3rd agent. Darunavir was most commonly used (n = 1285), followed by atazanavir (n = 806), efavirenz (n = 694), raltegravir (n = 622), rilpivirine (n = 592), lopinavir (n = 291) and etravirine (n = 262). Compared to darunavir all other drugs except for rilpivirine (HR 0.66; 95% CI 0.52–0.83, p<0.001) had higher risk for discontinuation in the multivariate adjusted analyses; atazanavir (HR 1.71; 95% CI 1.48–1.97, p<0.001), efavirenz (HR 1.86; 95% CI 1.59–2.17, p<0.001), raltegravir (HR 1.35; 95% CI 1.15–1.58, p<0.001), lopinavir (HR 3.58; 95% CI 3.02–4.25, p<0.001) and etravirine (HR 1.61; 95% CI 1.31–1.98, p<0.001).Besides the 3rd agent chosen also certain baseline characteristics of patients were independently associated with differences in treatment duration. In naive patients, presence of an AIDS-defining diagnosis and the use of other backbone than TDF/FTC or ABC/3TC increased the risk for early treatment discontinuation. In treatment-experienced patients, detectable plasma viral load at the time of switch or being highly treatment experienced increased the risk for early treatment discontinuation. Conclusions Treatment durability is dependent on several factors among others patient characteristics and ART guidelines. The choice of 3rd agent has a strong impact and significant differences between different drugs on treatment duration exist.