Incidence of oncogenic HPV infection in women with and without mental illness: A population-based cohort study in Sweden.

BACKGROUND: Women with mental illness experience an increased risk of cervical cancer. The excess risk is partly due to low participation in cervical screening; however, it remains unknown whether it is also attributable to an increased risk of infection with human papillomavirus (HPV). We aimed to examine whether women with mental illness had an increased infection rate of HPV compared to women without mental illness. METHODS AND FINDINGS: Using a cohort design, we analyzed all 337,116 women aged 30 to 64 and living in Stockholm, who had a negative test result of 14 high-risk HPV subtypes in HPV-based screening, during August 2014 to December 2019. We defined women as exposed to mental illness if they had a specialist diagnosis of mental disorder or had a filled prescription of psychotropic medication. We identified incident infection of any high-risk HPV during follow-up and fitted multivariable Cox models to estimate hazard ratios (HR) with 95% confidence intervals (CI) for HPV infection. A total of 3,263 women were tested positive for high-risk HPV during follow-up (median: 2.21 years; range: 0 to 5.42 years). The absolute infection rate of HPV was higher among women with a specialist diagnosis of mental disorder (HR = 1.45; 95% CI [1.34, 1.57]; p < 0.001) or a filled prescription of psychotropic medication (HR = 1.67; 95% CI [1.55, 1.79]; p < 0.001), compared to women without such. The increment in absolute infection rate was noted for depression, anxiety, stress-related disorder, substance-related disorder, and ADHD, and for use of antidepressants, anxiolytics, sedatives, and hypnotics, and was consistent across age groups. The main limitations included selection of the female population in Stockholm as they must have at least 1 negative test result of HPV, and relatively short follow-up as HPV-based screening was only introduced in 2014 in Stockholm. CONCLUSIONS: Mental illness is associated with an increased infection rate of high-risk HPV in women. Our findings motivate refined approaches to facilitate the WHO elimination agenda of cervical cancer among these marginalized women worldwide.

Cervical screening in high-income countries: the need for quality assurance, adjunct biomarkers and rational adaptation to HPV vaccination.

We here discuss human papillomavirus (HPV)-based screening avenues to achieve elimination of cervical cancer as a public health problem in high-income country (HIC) settings, covering both the most recent data on the performance of HPV testing, as well as the currently most robust triage methods that are known. We also provide an outlook to several other promising, yet not fully established, options for triage that have been proposed, including methylation, dual staining, machine learning, and artificial intelligence. Finally, we discuss the key issue of how to adapt screening in the presence of programmatic HPV vaccination, and how this combination can best be leveraged for comprehensive cancer control. We conclude that, for the HIC setting, evidence-based and effective cervical screening methods are readily available, but whichever method or platform is chosen, we would propose that recurring audits of performance and population attendance remain common denominators for maintaining successful disease prevention.

Quadrivalent HPV vaccine effectiveness against high-grade cervical lesions by age at vaccination: A population-based study.

Human papillomavirus (HPV) types 16/18, included in HPV vaccines, contribute to the majority of cervical cancer, and a substantial proportion of cervical intraepithelial neoplasia (CIN) grades 2/3 or worse (CIN2+/CIN3+) including adenocarcinoma in situ or worse. The aim of this study was to quantify the effect of quadrivalent HPV (qHPV) vaccination on incidence of CIN2+ and CIN3+. A nationwide cohort of girls and young women resident in Sweden 2006-2013 and aged 13-29 (n = 1,333,691) was followed for vaccination and histologically confirmed high-grade cervical lesions. Data were collected using the Swedish nationwide healthcare registers. Poisson regression was used to calculate incidence rate ratios (IRRs) and vaccine effectiveness [(1-IRR)x100%] comparing fully vaccinated with unvaccinated individuals. IRRs were adjusted for attained age and parental education, and stratified on vaccination initiation age. Effectiveness against CIN2+ was 64% (IRR = 0.36, 95%CI = 0.27­0.47) for those initiating vaccination before age 17, and 25% (IRR = 0.75, 95%CI = 0.66­0.86) and 14% (IRR = 0.86, 95%CI = 0.73­1.01) for those initiating vaccination at ages 17­19, and at ages 20­29, respectively. Vaccine effectiveness against CIN3+ was similar to vaccine effectiveness against CIN2+. Results were robust for both women participating to the organized screening program and for women at prescreening ages. We show high effectiveness of qHPV vaccination on CIN2+ and CIN3+ lesions, with greater effectiveness observed in girls younger at vaccination initiation. Continued monitoring of impact of HPV vaccination in the population is needed in order to evaluate both long-term vaccine effectiveness and to evaluate whether the vaccination program achieves anticipated effects in prevention of invasive cervical cancer.

Sexually transmitted infections after bereavement - a population-based cohort study.

BACKGROUND: Loss of a loved one has consistently been associated with various health risks. Little is however known about its relation to sexually transmitted infections (STIs). METHODS: We conducted a population-based cohort study during 1987-2012 using the Swedish Multi-Generation Register, including 3,002,209 women aged 10-44 years. Bereavement was defined as death of a child, parent, sibling or spouse (N = 979,579, 33 %). STIs were defined as hospital visits with an STI as main or secondary diagnosis. Poisson regression and negative binomial regression were used to estimate incidence rate ratios (IRRs) and 95 % confidence intervals (CIs) of STIs, comparing incidence rates of women who had experienced loss to those who had not. RESULTS: Bereaved women were at significantly higher risk of nearly all STIs studied. The relative risk of any STI was highest during the first year after loss (IRR: 1.45, 95 % CI: 1.27-1.65) and predominantly among women with subsequent onset of psychiatric disorders after bereavement (IRR: 2.61, 95 % CI: 2.00-3.34). Notably, a consistent excess risk, persisting for over five years, was observed for acute salpingitis (IRR: 1.28, 95 % CI: 1.13-1.44), a severe complication of bacterial STIs. CONCLUSION: These data suggest that women who have experienced bereavement are at increased risk of STIs.

Current cervical cancer prevention strategies including cervical screening and prophylactic human papillomavirus vaccination: a review.

PURPOSE OF REVIEW: As screening methods evolve and human papillomavirus (HPV) vaccination efforts gain traction, knowledge of the current evidence on effectiveness of prevention methods is critical to support further development of programs. RECENT FINDINGS: Screening has dramatically reduced cervical cancer incidence and mortality; however, further progress could be made with implementing new screening techniques, such as HPV DNA testing. Continued focus has been given to methods such as visual inspection with acetic acid/Lugol's iodine (VIA/VILI) and self-testing, which may provide an alternative in settings and populations wherein infrastructural challenges and logistical barriers pose challenges to achieving high screening coverage. Postlicensure studies of HPV vaccine show continued effectiveness against genital warts, the first outcome possible to measure. Of note, age-at-vaccination seems to play a pivotal role in effectiveness. Studies examining safety of the HPV vaccines could not confirm any increased risk associated with vaccination. SUMMARY: Existing cervical screening techniques are effective; however, programs should consider implementing HPV DNA testing where applicable and further process developments for alternative methods may result in improved results. The HPV vaccine is safe and effective and should be given before sexual debut to achieve maximum protection.

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.

The role of mental illness and neurodevelopmental conditions in human papillomavirus vaccination uptake within the Swedish school-based vaccination programme: a population-based cohort study.

BACKGROUND: Despite documented mental illness-related disparities in cervical cancer screening and incidence, insufficient data exist on differences in cervical cancer prevention strategies, such as human papillomavirus (HPV) vaccination. We aimed to investigate the association of mental illness and neurodevelopmental conditions among girls and their parents with uptake of HPV vaccination in Sweden. METHODS: This population-based cohort study was based on the Swedish school-based HPV vaccination programme, which offers the first vaccine dose to girls aged 10-13 years, with a second dose offered within 12 months. We identified all girls born between Jan 1, 2002, and March 1, 2004, using the Swedish Total Population Register-ie, those eligible for two vaccine doses in the vaccination programme from its initiation in autumn 2012, to March, 2019. Nationwide Swedish register data (National Patient Register, Prescribed Drug Register, HPV Vaccination Register, National Vaccination Register, Total Population Register, Multi-Generation Register, Longitudinal Integrated Database for Health Insurance and Labour Market Studies, Education Register, National Cervical Screening Registry, and Cancer Register) were used to define individual and parental mental health conditions, including mental illness and neurodevelopmental conditions (defined by a clinical diagnosis and prescribed psychotropic medication use), HPV vaccine uptake (first and second dose), and sociodemographic and clinical characteristics. The two outcomes were uptake of the first HPV vaccine dose by the girl's 14th birthday and uptake of the second dose by the 15th birthday in relation to individual and parental mental health conditions, calculated using multivariable Poisson regression models. FINDINGS: 115 104 girls were included in the study population. 2211 girls (1·9%) had a specialist diagnosis of any mental health condition. Uptake of the first HPV vaccine dose was 80·7% (92 912 of 115 104) and was lower among girls with versus without any mental health condition (adjusted relative risk 0·89 [95% CI 0·87-0·91]). The diagnosis of autism (0·79 [0·75-0·85]) or intellectual disability (0·78 [0·73-0·83]) were most strongly associated with lower HPV vaccine uptake. Vaccine uptake was also lower among girls with versus those without prescribed use of psychotropic medication (0·93 [0·92-0·95]), with the strongest association observed for antipsychotics (0·68 [0·56-0·82]). Uptake of the second dose was 95·0% (88 308 of 92 912), with no strong associations between uptake and mental health conditions in girls or their parents. INTERPRETATION: Our findings suggest disparities in cervical cancer prevention among girls with mental health conditions, and call for further research to ensure equitable protection. FUNDING: Swedish Cancer Society.

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 10­44 years living in Sweden during 2006­2010. 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 2006­2007 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.

High coverage and adherence to dose intervals of the national school-based HPV vaccination program in Sweden during 2012-2019.

Background: Close monitoring of vaccination coverage is important for cervical cancer prevention efforts. The study aims to describe the HPV vaccination coverage by dose in girls eligible for HPV vaccination within Sweden's childhood immunization program and provide an estimate on dose timing compliance. Methods: Vaccination records between 2012 and March 2019 were obtained for girls born in 2000-2006 from the vaccination registers in Sweden. The mid-time population counts for the respective birth cohorts were taken as the denominator. Full-dose coverage and coverage with at least one dose of the vaccine were calculated within the two-dose and three-dose regimen, by region. Dose compliance was calculated within the two-dose regimen. Results: Vaccination coverage with at least one dose of the vaccine was >80% within birth cohorts 2001-2006. Full-dose coverage within a two-dose and three-dose regimen were 73.4% in birth cohorts 2004-2005, and 56.3% in birth cohorts 2000-2001, respectively. Little variation was observed in vaccination coverage between regions. Dose completion was 91.8%, and 72.8% in girls that initiated a two-dose and three-dose regimen, respectively. Among girls receiving a two-dose regimen, 93.0% received the second dose 6-12 months after dose one. Discussion: In conclusion, high levels of HPV vaccination coverage were observed with little variation between regions. Dose timing compliance was particularly high in the two-dose regimen. To fully benefit from the impact of HPV vaccination, it will be important to further push the vaccination coverage and reach the girls that do not or partially engage with HPV vaccination.

Overall and Cervical Cancer Survival in Patients With and Without Mental Disorders.

Importance: Individuals with a mental disorder experience substantial health disparity and are less likely to participate in cervical screening and human papillomavirus vaccination. Additionally, this population may benefit less from tertiary cancer prevention. Objective: To compare clinical characteristics and survival patterns between patients with cervical cancer with and without a preexisting diagnosis of a mental disorder at the time of cervical cancer diagnosis. Design, Setting, and Participants: This cohort study obtained data from Swedish population-based (Swedish Cancer Register, Swedish Cause of Death Register, Swedish Total Population Register, Swedish Patient Register, and Swedish Longitudinal Integration Database for Health Insurance and Labor Market Studies) and quality registries (Swedish Quality Register of Gynecologic Cancer and Swedish National Cervical Screening Register) on patients with cervical cancer. Patients who were included in the analysis were identified using the Swedish Cancer Register and were diagnosed with cervical cancer between 1978 and 2018. The Swedish Patient Register was used to identify patients with mental disorders using codes from the International Classification of Diseases, Eighth Revision and Ninth Revision and the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision. Because data on clinical characteristics at the time of cancer diagnosis were available for only for part of the study population, 2 patient groups were created: those with cervical cancer diagnosed from 2002 to 2016 and all patients diagnosed with cervical cancer (1978-2018). Data analyses were carried out between March and September 2022. Exposure: Clinical diagnoses of a mental disorder, including substance abuse, psychotic disorders, depression, anxiety, stress-related disorders, attention-deficit/hyperactivity disorder, autism, and intellectual disability, prior to cervical cancer. Main Outcomes and Measures: Death due to any cause or due to cervical cancer as ascertained from the Swedish Cause of Death Register. Results: The sample included 20 177 females (mean [SD] age, 53.4 [17.7] years) diagnosed with cervical cancer from 1978 to 2018. In a subgroup of 6725 females (mean [SD] age, 52.2 [18.0] years) with cervical cancer diagnosed from 2002 to 2016, 893 (13.3%) had a preexisting diagnosis of a mental disorder. Compared with patients with no preexisting mental disorder diagnosis, those with a preexisting mental disorder had a higher risk of death due to any cause (hazard ratio [HR], 1.32; 95% CI, 1.17-1.48) and due to cervical cancer (HR, 1.23; 95% CI, 1.07-1.42). These risks were lower after adjustment for cancer characteristics at the time of cancer diagnosis (death due to any cause: HR, 1.19 [95% CI, 1.06-1.34] and death due to cervical cancer: HR, 1.12 [95% CI, 0.97-1.30]). Risk of death was higher for patients with substance abuse, psychotic disorders, or mental disorders requiring inpatient care. Among patients with cervical cancer diagnosed from 1978 to 2018, the estimated 5-year survival improved continuously during the study period regardless of preexisting diagnosis of a mental disorder status. For example, in 2018, the estimated 5-year overall survival proportion was 0.66 (95% CI, 0.60-0.71) and 0.74 (95% CI, 0.72-0.76) for patients with and without a preexisting diagnosis of a mental disorder, respectively. Conclusions and Relevance: Findings of this cohort study suggest that patients with cervical cancer and a preexisting diagnosis of a mental disorder have worse overall and cervical cancer-specific survival than patients without a preexisting mental disorder diagnosis, which may be partly attributable to cancer and sociodemographic characteristics at diagnosis. Hence, individuals with mental disorders deserve special attention in the tertiary prevention of cervical cancer.

Invasive cervical cancer, precancerous lesions, and cervical screening participation among women with mental illness in Sweden: a population-based observational study.

BACKGROUND: WHO aims to eliminate cervical cancer. Whether women with mental illness constitute a group at high-risk and require targeted prevention initiatives remains unknown. We aimed to assess whether women with severe mental illness, psychiatric or neurodevelopmental disorders, have an increased risk of invasive cervical cancer, and an increased risk of precancerous lesions and a lower degree of participation in cervical screening compared with women without severe mental illness. METHODS: In this population-based observational study, 4 112 598 women from 1973 to 2018 in Sweden were included to compare the risk of invasive cervical cancer, high-grade precancerous cervical lesions (CIN2+), and degree of participation in cervical screening (defined as the proportion of time covered by screening during a period when cervical screening is recommended) between women with and without mental illness. We focused on severe mental illness (ie, diagnosed in specialised psychiatric care) and also investigated milder mental illness (ie, use of psychotropic medications prescribed in primary care without specialist diagnosis) as secondary exposure. In two nested case-control studies, we defined the cases as women who have a diagnosis of invasive cervical cancer or CIN2+, and randomly selected individually matched controls from women who did not have these diagnoses. FINDINGS: Women with a specialist diagnosis of mental illness had a higher risk of invasive cervical cancer (hazard ratio 2·39, 95% CI 2·22-2·57) and CIN2+ (2·22, 2·18-2·26) and a 5·0% (4·8-5·2) lower cervical screening participation compared with matched controls. The risk increment of invasive cervical cancer and CIN2+ was greatest for substance misuse, whereas the screening reduction was greatest for intellectual disability and autism. In contrast, women who used prescribed psychotropic medications without specialist diagnosis had slightly higher screening participation and higher risk of CIN2+ but lower risk of invasive cervical cancer than women with neither specialist diagnosis nor medication use. INTERPRETATION: Women with severe mental illness participate less in screening and experience a higher risk of cervical neoplasia. Refined approaches are needed to better target these women in the elimination agenda of cervical cancer. FUNDING: Swedish Cancer Society.

Evaluation of Heterologous Effects of Travel Vaccines in Colorectal Cancer: A Database Study and a Cautionary Tale.

Background and Aims: Recently, cholera vaccine use was shown to be associated with a reduced risk of death in patients with colorectal cancer (CRC). However, evidence on heterologous effects of travel vaccines is limited. The aim of this study was to study heterologous effects of travel vaccines in patients with CRC. Methods: We performed a retrospective database study on a cohort of CRC patients in Sweden and their postdiagnostic use of travel medications between July 2005 and December 2017. We obtained data from national registries on number of CRC diagnosis, death from CRC or other causes, age at diagnosis, and postdiagnostic use of travel vaccines and malaria prophylaxis. The Cox regression model was used to calculate incidence rate and incidence rate ratios of CRC-related and all-cause mortality by postdiagnostic travel medication status. Results: Two hundred ninety-five patients exposed to travel vaccines and malaria prophylaxis and 73,466 patients not exposed to travel medications were identified. CRC-related mortality was lowered in the exposed patients compared to the unexposed patients, irrespective of the travel medications used. The incidence rate ratios for CRC-related mortality and overall mortality were comparable. Conclusion: We postulated that patients in better health were likely to travel more frequently than patients with poor health, leading to a healthy user bias. The results suggested the same, as similar reduced mortality risks were found for all the investigated travel medications, lowering the biological plausibility of truly protective effect from post-therapeutic use of any of the travel medication studied. We advocate the use of multiple negative exposure controls and to exercise caution while drawing conclusions from travel vaccine research.

Substantially reduced incidence of genital warts in women and men six years after HPV vaccine availability in Sweden.

BACKGROUND: Between 2007 and 2011, opportunistic HPV-vaccination was available in Sweden and partially subsidized to girls aged 13-17, reaching a ∼30% overall coverage. METHODS: All Swedish women/men aged 15-44 were followed between 2006 and 2012 for condyloma. Average annual percent changes (AAPCs) in incidence were estimated. RESULTS: Substantial decreases were seen in women aged 15-24 from 2008-onwards (AACP-range: -8.5% to -18.5%); similar effects were seen for men aged 15-29 (AACP-range: -7.0% to -16.6%) from 2010-onwards. DISCUSSION: Despite low population vaccination coverage in women and no coverage in men, similar condyloma incidence reductions were observed among men and women, with delays of >1 years in men.

Effectiveness of varying number of doses and timing between doses of quadrivalent HPV vaccine against severe cervical lesions.

BACKGROUND: Based on immunogenicity studies, a 2 dose HPV vaccination-schedule was recently recommended for girls younger than 15 years. We aimed to investigate the effectiveness of quadrivalent HPV (qHPV) vaccination against CIN2 or worse (CIN2+), by age at vaccination, number of doses, and to test whether optimal timing of 2 doses of qHPV vaccine can confer the same level of protection as the originally recommended three dose-schedule. METHODS: A population-based cohort of all women aged 13-30 years, living in Denmark or Sweden during 2006-2013, was followed for qHPV vaccination status and first occurrence of CIN2+. RESULTS: The study cohort comprised 2,253,561 women, of which 33% were vaccinated during follow-up, and 1.7% were diagnosed with CIN2+. Vaccination at ages 13-16 and 17-19 was associated with a reduced risk of CIN2+ after 3 doses (IRR = 0.23, 95% CI 0.11-0.49, and IRR = 0.65, 95% CI 0.41-1.03, respectively), compared to being unvaccinated. After 1 and 2 doses there was a reduced risk, but not statistically significant. Women vaccinated ages 13-16 with 2 doses, where time between first and second dose was 5 months or longer showed no difference in risk compared to 3 doses. CONCLUSIONS: Women vaccinated with 3 doses of qHPV showed a reduced risk of CIN2+ if they were vaccinated before age 20, with a further reduced risk if vaccinated before age 17. Vaccination with 2 doses, with the second dose 5 months or longer after the first dose, did not yield an increased risk of CIN2+, compared to 3 doses.

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.

The Participation of HPV-Vaccinated Women in a National Cervical Screening Program: Population-Based Cohort Study.

BACKGROUND: Concerns have been raised that HPV-vaccination might affect women's cervical screening behavior. We therefore investigated the association between opportunistic HPV-vaccination and attendance after invitation to cervical screening. METHODS: A cohort of all women resident in Sweden, born 1977-1987 (N=629,703), and invited to cervical screening, was followed October 2006 - December 2012. Invitations to screening were identified via the National Quality Register for Cervical Cancer Prevention, as was the primary outcome of a registered smear. Vaccination status was obtained from two nationwide health data registers. Hazard ratios (HR) were estimated using Cox regression adjusted for age, education level and income (HRadj). Women were individually followed for up to 6 years, of which the first and second screening rounds were analyzed separately. RESULTS: Screening attendance after three years of follow-up was 86% in vaccinated women (N=4,897) and 75% in unvaccinated women (N=625,804). The crude HR of screening attendance in vaccinated vs. unvaccinated women was 1.31 (95% CI 1.27-1.35) in the first screening round. Adjustment for education and income reduced but did not erase this difference (HRadj=1.09, 95% CI 1.05-1.13). In the second screening round, attendance was likewise higher in HPV-vaccinated women (crude HR=1.26, 95% CI 1.21-1.32; HRadj=1.15, 95% CI 1.10-1.20). CONCLUSIONS: HPV-vaccination is so far associated with equal or higher attendance to cervical screening in Sweden in a cohort of opportunistically vaccinated young women. Most but not all of the difference in attendance was explained by socioeconomic differences between vaccinated and unvaccinated women. HPV vaccine effectiveness studies should consider screening attendance of HPV-vaccinated women when assessing incidence of screen-detected cervical lesions.

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.