Karin Sundström

Attitudes to HPV vaccination among parents of children aged 12-15 years-a population-based survey in Sweden.

In this population‐based survey undertaken in Sweden in 2007, we investigated correlates of attitudes to human papillomavirus (HPV) vaccination among parents of children aged 12–15 years. We invited 16,000 parents of girls and 4,000 parents of boys, randomly selected from the Swedish population. Response rates were 70 and 69%, respectively. Multinomial logistic regression models were applied to investigate correlates of acceptability to HPV vaccination. Among studied parents, 76% were willing to vaccinate their child if the vaccine is for free and 63% were willing to vaccinate even if the vaccine comes with a cost. Having heard of HPV was associated with both willingness to vaccinate if the vaccine is free (odds ratio [OR]: 1.42; 95% confidence interval [CI]: 1.21–1.66) and willingness to vaccinate even if the vaccine is not free (OR: 1.96; 95% CI: 1.75–2.20) compared with those who never heard of HPV. Beliefs about vaccine safety and efficacy were also strong correlates of willingness to vaccinate. Parents born outside Europe and those with higher education were less willing to vaccinate if the vaccine is not free. In conclusion, the willingness to vaccinate was reasonably high and cost did not appear to be a major barrier. Information about vaccine safety and efficacy is important and parents need information about HPV and the HPV vaccine.

Prospective study of human papillomavirus and risk of cervical adenocarcinoma

Human papillomaviruses (HPV) are established as a major cause of cervical carcinoma. However, causality inference is dependent on prospective evidence showing that exposure predicts risk for future disease. Such evidence is available for squamous cell carcinoma, but not for cervical adenocarcinoma. We followed a population‐based cohort of 994,120 women who participated in cytological screening in Sweden for a median of 6.7 years. Baseline smears from women who developed adenocarcinoma during follow‐up (118 women with in situ disease and 164 with invasive disease) and their individually matched controls (1,434 smears) were analyzed for HPV using PCR. Conditional logistic regression was used to estimate odds ratios (OR) of future adenocarcinoma with 95% confidence intervals (CI). Being positive for HPV 16 in the first cytologically normal smear was associated with increased risks for both future adenocarcinoma in situ (OR: 11.0, 95% CI: 2.6–46.8) and invasive adenocarcinoma (OR: 16.0, 95% CI: 3.8–66.7), compared to being negative for HPV 16. Similarly, an HPV 18 positive smear was associated with increased risks for adenocarcinoma in situ (OR: 26.0, 95% CI: 3.5–192) and invasive adenocarcinoma (OR: 28.0, 95% CI: 3.8–206), compared to an HPV 18 negative smear. Being positive for HPV 16/18 in 2 subsequent smears was associated with an infinite risk of both in situ and invasive adenocarcinoma. In conclusion, infections with HPV 16 and 18 are detectable up to at least 14 years before diagnosis of cervical adenocarcinoma. Our data provide prospective evidence that the association of HPV 16/18 with cervical adenocarcinoma is strong and causal.

Acceptability of HPV vaccination among young adults aged 18–30 years–a population based survey in Sweden

Acceptability of human papillomavirus (HPV) vaccination seems to be high in the Western world but fewer data are available for men than for women. There are also concerns that HPV vaccination might lead young people to change their healthcare-related behaviours. We investigated these issues in a population-based survey performed in Sweden during January-May, 2007, just after HPV vaccination had been licensed. A total of 10567 men and women aged 18 to 30 years participated. The intention to accept HPV vaccination among these young adults was relatively high but could likely be improved with higher awareness of HPV-related diseases as well as of the safety and efficacy of vaccines in general. Also, the cost of the vaccine needs to be affordable. Even though few young adults stated their healthcare-related behaviours would change after HPV vaccination, a significant number were uncertain, suggesting a need for continued educational efforts when HPV-vaccinating this group.

Prospective study of human papillomavirus (HPV) types, HPV persistence, and risk of squamous cell carcinoma of the cervix.

Background: The link between squamous cell cervical carcinoma and human papillomavirus (HPV) 16/18 is well established, but the magnitude of the risk association is uncertain and the importance of other high-risk HPV (HRHPV) types is unclear. Methods: In two prospective nested case-control series among women participating in cytologic screening in Sweden, we collected 2,772 cervical smears from 515 women with cancer in situ (CIS), 315 with invasive squamous cell carcinoma (SCC), and individually matched controls. All smears were tested for HPV with PCR assays, and the median follow-up until diagnosis was 5 to 7 years. Conditional logistic regression was used to estimate relative risks (RR) and 95% confidence intervals (95% CI). Results: The presence of HPV16/18 in the first smear was associated with 8.5-fold (95% CI, 5.3-13.7) and 18.6-fold (95% CI, 9.0-38.9) increased risks of CIS and SCC, respectively, compared with women negative for HPV. Infection with other HRHPV types in the first smear was also associated with significantly increased risks for both CIS and SCC. Persistence of HPV16 infection conferred a RR of 18.5 (95% CI, 6.5-52.9) for CIS and 19.5 (95% CI, 4.7-81.7) for SCC. The HPV16/18 attributable risk proportion was estimated at 30% to 50% for CIS, and 41% to 47% for SCC. Other HRHPV types also conferred significant proportions. Conclusions: Our large population-based study provides quantification of risks for different HPV types and prospective evidence that non-16/18 HRHPV types increase the risk for future cervical cancer. Impact: This study gives further insights into cervical cancer risk stratification with implications for HPV-based prevention strategies. Cancer Epidemiol Biomarkers Prev; 19(10); 2469–78. ©2010 AACR.

Hantavirus-infection Confers Resistance to Cytotoxic Lymphocyte-Mediated Apoptosis

Hantaviruses cause hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardio-pulmonary syndrome (HCPS; also called hantavirus pulmonary syndrome (HPS)), both human diseases with high case-fatality rates. Endothelial cells are the main targets for hantaviruses. An intriguing observation in patients with HFRS and HCPS is that on one hand the virus infection leads to strong activation of CD8 T cells and NK cells, on the other hand no obvious destruction of infected endothelial cells is observed. Here, we provide an explanation for this dichotomy by showing that hantavirus-infected endothelial cells are protected from cytotoxic lymphocyte-mediated induction of apoptosis. When dissecting potential mechanisms behind this phenomenon, we discovered that the hantavirus nucleocapsid protein inhibits the enzymatic activity of both granzyme B and caspase 3. This provides a tentative explanation for the hantavirus-mediated block of cytotoxic granule-mediated apoptosis-induction, and hence the protection of infected cells from cytotoxic lymphocytes. These findings may explain why infected endothelial cells in hantavirus-infected patients are not destroyed by the strong cytotoxic lymphocyte response.

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.

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 75% (IRR = 0.25, 95%CI = 0.18–0.35) for those initiating vaccination before age 17, and 46% (IRR = 0.54, 95%CI = 0.46–0.64) and 22% (IRR = 0.78, 95%CI = 0.65–0.93) for those initiating vaccination at ages 17–19, and at ages 20–29, 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.

Prospective study of HPV16 viral load and risk of in situ and invasive squamous cervical cancer

Background: A strong association has been shown between high viral DNA load (VL) of human papillomavirus (HPV) type 16 and risk for cervical cancer in situ (CIS). However, little data is available for the significance of VL in invasive squamous cell carcinoma (SCC). Methods: In 2 nested case–control studies among women participating in cervical screening, with a cytologically normal first smear, we collected 5,665 smears from 621 women with CIS, 457 with SCC, and individually matched controls. All smears were tested for HPV, and VLs of HPV16 positive smears were quantified using real time-PCR. The median follow-up until diagnosis of CIS or SCC was 6.1 to 7.7 years. Results: Low VLs were common among both CIS and SCC case women, until 1 to 2 years before diagnosis when a surge in VL occurred. The relative risk (RR) associated with low viral load of HPV16 was around 10 for CIS, and 10 to 20 for SCC throughout 10 years before diagnosis, compared with HPV16-negative women. For women with medium to high VL, the risk for CIS was greatly increased from 5 years before diagnosis [RR, 19; 95% confidence interval (CI), 7–48]. In SCC, a high VL conferred an increased risk, but only from 3 years before diagnosis [RR, 60; 95% CI, 6–580]. Conclusions: We show differing risk functions associated with HPV16 viral load in CIS and SCC, respectively. We further show that viral loads were unexpectedly low early in the SCC disease process. Impact: HPV16 viral load appears highly complex which may limit its use in cervical screening. Cancer Epidemiol Biomarkers Prev; 22(1); 150–8. ©2012 AACR.

Awareness and Knowledge of Human Papillomavirus in the Swedish Adult Population

PURPOSE To assess awareness and knowledge of human papillomavirus (HPV) in the adult Swedish population. METHODS A cross-sectional study among young adults aged 18-30 years and the parents of children aged 12-15 years was conducted in 2007 to collect information on awareness and knowledge of HPV. Correlates of HPV knowledge were investigated. RESULTS Awareness of cervical cancer and condyloma were high but awareness of HPV was low. Many participants were uncertain or did not know about the causal relation between HPV and condyloma, and cancers other than cervical cancer. Among parents, gender, age, country of origin, and education were the most important correlates of HPV knowledge. Among young adults, these factors were gender, income, and education. CONCLUSIONS HPV education campaigns should particularly target young men and those with low education. Educational messages should clarify the risk of HPV, and the causal relationship between HPV and condyloma, and other cancers.

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.