Quadrivalent HPV vaccine effectiveness against cervical intraepithelial lesion grade 2 or worse in Norway: A registry-based study of 0,9 million Norwegian women.

In Norway, single cohort vaccination with quadrivalent HPV (qHPV) vaccine targeting 12-year-old girls took place from 2009-2016. In 2020, the oldest vaccinated cohort was 23 years old and had approached the age where risk of being diagnosed with cervical intraepithelial lesion grade 2 or worse (CIN2+) increases rapidly. The aim of this cohort study was to assess direct qHPV vaccine effectiveness (VE) against CIN2+ among Norwegian women aged 16-30 in 2007-2020. By using population-based health registries and individual-level data on vaccination status and potential subsequent CIN2+ incidence, we found 82% qHPV VE among women vaccinated before the age of 17.

Quadrivalent HPV vaccine effectiveness against anogenital warts: A registry-based study of 2,2 million individuals.

BACKGROUND: In 2009, Norway initiated routine quadrivalent HPV (qHPV) vaccination for girls at 12-13 years of age to protect against virus types causing cervical cancer, HPV16/18, and HPV6/11 which cause anogenital warts (AGW). We wanted to investigate qHPV vaccine effectiveness (VE) against AGW in females before and after first AGW episode and to assess the impact of female vaccination in males. MATERIALS AND METHODS: QHPV vaccination and AGW episodes were collected for the time period 2006-2016 for birth cohorts 1975-2003. Cox models were applied to age at first, as well as at second AGW episode. Finally, we estimated the impact of the female vaccination program on unvaccinated males. RESULTS: The VE against the first episode of AGW was strongly dependent on vaccination age, with hazard ratios (HRs) compared to unvaccinated individuals of 0.2, 0.2, 0.3, 0.5, 1.0, 1.3, and 2.7, for age groups of ⩽13, 14-15, 16-17, 18-19, 20-24, 25-29, and 30+ years at first vaccination, respectively. Among women who had suffered a first episode of AGW, subsequent qHPV vaccination did not protect against a second episode, with HRs of 0.8, 1.0, and 1.4, for age groups of ⩽17, 18-24, and 25+ years at first vaccination. A gradually decreasing AGW risk was seen in unvaccinated male cohorts neighboring the first routinely vaccinated female 1997 cohort. CONCLUSIONS: When administered before 14 years of age, qHPV vaccination reduced the probability of AGW about fivefold. The effect decreased sharply with vaccination age, and was not significant among women vaccinated after age 20 years. QHPV administered after the first AGW episode did not protect against a second AGW episode. Herd effects were indicated in unvaccinated males, as we observed a gradual decrease in AGW rates from the 1993 male birth cohort and onwards.

Cervical cancer screening history among women diagnosed with cervical cancer in Estonia 2017-18.

BACKGROUND: Despite the national cervical cancer screening programme launched in 2006, Estonia has one of the highest cervical cancer incidence rates in Europe. While the overall coverage of cervical cytology is high, the factors related to cancer screening history prior to cancer diagnosis need to be studied. METHODS: In this study, we aimed to examine the 10-year screening history of women diagnosed with cervical cancer in Estonia in 2017-18, using data collected from laboratory reports from 2007 to 2018. From each report, we extracted information on the date and result of cytology and on the laboratory where the sample was assessed. We analysed these data across cancer histology, the time interval between the last test result and cancer diagnosis and the laboratory type (local or regional). RESULTS: Among 319 women with cervical cancer, 181 (56.7%) did not have any cytology reports available. Among 138 women with at least one cytology, 60% had 1-3, 24% 4-6 and 16% ≥7 tests (mean 3.7) before cancer. In 78% of women, the last test was performed less than 5 years before cancer diagnosis and 62% of these tests did not report any abnormalities. The last cytology results differed significantly between the regional and local laboratories (P = 0.028). CONCLUSION: Women received the cervical cancer diagnosis in Estonia despite having several screening tests 10 years prior to the diagnosis. The proportion of cytology tests without any abnormalities less than 5 years before the diagnosis was worryingly high and needs further investigation together with the difference between laboratory types.

Impact of the Mobile Game FightHPV on Cervical Cancer Screening Attendance: Retrospective Cohort Study.

BACKGROUND: The wide availability of mobile phones has made it easy to disseminate health-related information and make it accessible. With gamification, mobile apps can nudge people to make informed health choices, including attending cervical cancer screening. OBJECTIVE: This matched retrospective cohort study examined the association between exposure to the FightHPV mobile app gamified educational content and having a cervical exam in the following year. METHODS: Women aged 20 to 69 years who signed an electronic consent form after downloading the FightHPV app in 2017 (intervention group) were matched 1:6 with women of the same age and with the same screening history (reference group) in 2015. To estimate the impact of exposure to the FightHPV app, we estimated cumulative incidence and hazard ratios (HRs) with 95% CIs. We used data from the Norwegian Cervical Cancer Screening Program database and Statistics Norway to determine screening participation and outcomes, respectively. RESULTS: We matched 3860 women in the control group to 658 women in the intervention group; 6 months after enrollment, 29.6% (195/658) of the women in the intervention group and 15.21% (587/3860) of those in the reference group underwent a cervical exam (P<.01). Women exposed to the FightHPV app were 2 times more likely to attend screening (adjusted HR 2.3, 95% CI 2.0-2.7), during which they were 13 times more likely to be diagnosed with high-grade abnormality (adjusted HR 12.7, 95% CI 5.0-32.5) than the women in the reference group. CONCLUSIONS: Exposure to the FightHPV app significantly increased cervical cancer screening attendance across the various analyses and improved detection of women with high risk for cervical cancer. For the first time, we demonstrated the effectiveness of gamification combined with mobile technology in cancer prevention by empowering women to make active health-related decisions. Gamification can significantly improve the understanding of complicated scientific concepts behind interventions and increase the acceptance of proposed cancer control measures.

Inequalities in reported use of cervical screening in Estonia: results from cross-sectional studies in 2004-2020.

BACKGROUND: Despite the national cervical cancer (CC) screening program established in 2006, the CC incidence in Estonia in 2020 was still one of the highest in Europe. To better understand the possible barriers among women, the aim of this study was to describe the inequalities in the Pap smear uptake trend in 2004-2020 and to analyse the associations between different factors in Estonia. METHODS: Weighted data of 25-64-year-old women (N = 6685) from population-based cross-sectional studies of Health Behaviour among Estonian Adult Population in 2004-2020 was used. Linear trends in uptake of Pap smear over time were tested using the Cochrane-Armitage test. Binary logistic regression with interactions was performed to analyse associations between the uptake of Pap smear and sociodemographic, socioeconomic, health-related and lifestyle factors. Crude and adjusted odds ratios with 95% confidence intervals were calculated. RESULTS: Prevalence of lifetime uptake of Pap smear increased in 2004-2020 from 50.6 to 86.7% (P < 0.001). From 2004 to 2020, uptake of Pap smear increased significantly among women aged 25-34, 35-44, 45-54 and 55-64, in both ethnicity groups and among women with basic, secondary and higher education (P < 0.001). The gap in Pap smear uptake increased between Estonians and non-Estonians but decreased between education levels over time. Lower lifetime uptake of Pap smear was associated from sociodemographic factors with younger age, being non-Estonian and single, from socioeconomic factors with lower educational level and unemployment, from health indicators with higher body mass index indicating overweight and obesity, presence of chronic disease and depressiveness, and from lifestyle factors with non-smoking. CONCLUSIONS: Although Pap smear uptake among 25-64 year old women increased significantly in Estonia in 2004-2020, inequalities were found indicating an opportunity for development of targeted CC prevention strategies.

Quality Assessment of Cervical Cytology Practices in Estonia From 2007 to 2018.

BACKGROUND: Cervical cancer incidence and mortality in Estonia are among the highest in Europe, although the overall coverage with cervical cytology is high. This indicates potential issues with the quality of collection and/or laboratory evaluation of cervical cytology. OBJECTIVES: The aim of the retrospective observational study was to assess the quality of cervical cytology specimen collection, evaluation, and reporting using laboratory reports in Estonia. METHODS: The study included women with a cervical cancer diagnosis in 2017-2018. Cervical cytology and histology reports for these women in 2007-2018 were obtained from ten laboratories. We described the quality of cytology specimen collection and reporting of cytology results. Multivariate logistic regression was used to calculate odds ratios (OR) with 95% confidence intervals (CI) to identify factors associated with NILM as the last cervical cytology result within 5 or 2 years before the cervical cancer diagnosis. Also, we calculated cytology-histology correlation (CHC). RESULTS: We identified 503 cytology and 100 histology reports from 138 women. The laboratories differed greatly regarding human resources, work capacity and volume. Differences between local and regional laboratories were observed in reporting specimen adequacy (P < .001). We found that local laboratories had 3 times higher odds (OR = 2.95, 95% CI: 1.05-8.33) of reporting normal results 2 years before cancer diagnosis than regional laboratories. According to the CHC, 58.9% of pairs were in agreement. CONCLUSIONS: The study showed considerable heterogeneity and suboptimal performance of cervical cytology practices in Estonia, particularly at local laboratories. Efforts to improve laboratory quality assurance are crucial.

Effect of Pap-smear and sociodemographic factors on cervical cancer risk in Estonia: A population-based case-control study.

BACKGROUND: Like many Eastern-European countries, Estonia struggles with ineffective cervical cancer (CC) screening. Despite a long-term organised screening programme and high overall Pap-smear coverage, CC incidence and mortality remain very high. The aim of the study was to examine the reasons for high CC incidence in Estonia by analysing the effect of Pap-smears and sociodemographic factors on CC risk. METHODS: In this population-based case-control study, women aged ≥ 25 years with an in situ/invasive CC diagnosed in Estonia in 2011-2017 were defined as cases. Using a density sampling scheme, controls were randomly selected from general population. To estimate CC risk associated with having no Pap-smears during seven years before diagnosis (cases) or index date (controls), place of residence, interruption in health insurance, and several sociodemographic factors, multivariate logistic regression was used to calculate odds ratios (OR) with 95% confidence intervals (CI). Individual-level data from three population-based registries were used. RESULTS: Among 1439 cases and 4317 controls, proportion of women with no Pap-smears was 53% and 35%, respectively. Women with no Pap-smears were at higher risk for CC (OR=2.35; 95% CI: 1.85-2.98). CC risk was increased among women who were younger, living in more remote regions, lower-educated, or divorced/widowed. Interruption in health insurance was associated with a 23% risk increase. Regional differences in CC risk were observed among screened women. CONCLUSION: To reduce the risk of CC in Estonia, efforts are necessary to increase screening coverage among high-risk women and ensure the quality of CC screening programme. Screening approaches and communication should be tailored to the needs of different population groups. Further studies are warranted to identify the reasons for regional differences in CC risk.

The impact of HPV multi-cohort vaccination: Real-world evidence of faster control of HPV-related morbidity.

BACKGROUND: In 2009, both Norway and Denmark initiated routine quadrivalent human papillomavirus vaccination (qHPV) for 12-year-old girls; however, Denmark also introduced free-of-charge multi-cohort vaccination for older age groups in 2008. We aim to describe trends in genital warts (GWs) incidence rates (IRs) among men and women and qHPV vaccine coverage among women in Norway and Denmark in 2006-2015. METHODS: We linked multiple national health registries in Norway and Denmark via national personal identifiers to access data on GWs incidence and qHPV vaccination among women and men aged 12-35 years residing in Norway and Denmark in 2006-2015. We calculated age-specific and age-standardized GWs IRs, GWs IR trends before (2006-2009) and after (2009-2015) the implementation of qHPV vaccination, and qHPV vaccine coverage among women. RESULTS: In Norway and Denmark together, there were more than 200,000 cases of incident GWs and over 710,000 girls got at least one dose of qHPV vaccine during the study period. The total qHPV coverage in Norway and Denmark in 2015 was among women aged 12-35 years 24% and 70%, respectively. GWs IRs in Norway and Denmark decreased annually in 2009-2015 among women by 4.8% (95% confidence interval: 4.3 to 5.3) and 18.0% (95%CI: 17.5 to 18.6), respectively, and among men 1.9% (95%CI: 1.4 to 2.4) and 10.7% (95%CI: 10.3 to 11.2), respectively. In Denmark, GWs IRs decreased rapidly among both sexes and all age groups after qHPV vaccination, while Norway showed only a modest decrease. CONCLUSION: Rapid decline in HPV-related morbidity is feasible with high coverage of multi-cohort vaccination. However, the decision to vaccinate a single cohort of 12-years-old girls only will postpone HPV-related disease control by at least a decade. Thus countries planning HPV vaccination programs should also initiate multi-cohort vaccination for faster disease control.

Recent increase in incidence of cervical precancerous lesions in Norway: Nationwide study from 1992 to 2016.

We analysed patterns in the incidence of cervical intraepithelial neoplasia grades 2 and 3 (CIN2, CIN3) and adenocarcinoma in situ (AIS) by age and histology in 1992-2016 in Norway and described changes in screening tests. Incident cases of CIN2, CIN3, AIS and cervical cancer were identified in the Cancer Registry of Norway, as were all women with at least one screening test. The annual percentage change statistic was used to assess point estimates and changes in age-specific and age-standardised incidence rates (IR). Women aged 25-29 years had the highest incidence of cervical precancerous lesions (CIN2: 192.9/10, CIN3: 737.2/10, AIS: 32.5/105 in 2016). The IR of CIN2 increased for all screening ages (25-69 years) from 3.6% to 6.7% per year. CIN3 incidence increased by 1.6% (95% confidence interval [CI] 0.6-2.6) annually. A steep increase in AIS incidence was observed in all age groups (7.1% per year, 95% CI 5.3-8.8). Changes in screening tests and the histological verification of cervical precancerous lesions alone cannot explain the steady increase in incidence we observed over the 25-year study period, and increased exposure to human papillomavirus (HPV) likely plays a role. Age-appropriate treatment of screening-detected cervical precancerous lesions is needed for effective cervical cancer control while avoiding overtreatment and related health risks. In order to perform an appropriate harm-benefit evaluation of cervical cancer control efforts, detailed information on screening technology and background risks, including HPV vaccination status, is needed to create optimal public health policy.

Trends in incidence, mortality and survival of penile squamous cell carcinoma in Norway 1956-2015.

We examine trends in incidence, mortality and survival of penile squamous cell carcinoma (SCC) in Norway over 60 years. Data on all cases of penile cancer diagnosed in Norway during 1956-2015 were obtained from the Cancer Registry of Norway. Trends in age-standardized rates of penile SCC incidence, mortality and 5-year relative survival were assessed by the annual percentage change statistic and joinpoint regression. A total of 1,596 penile cancer cases were diagnosed during 1956-2015, among which 1,474 (92.4%) were SCC. During 2011-2015, the age-standardized incidence and mortality of penile SCC were 0.91 (95% confidence interval (CI): 0.78; 1.05) and 0.50 (0.42; 0.60) per 100,000, respectively, and the 5-year relative survival was 61.6% (41.9; 76.4). The incidence of SCC increased during 1956-2015, with an average annual percentage change (AAPC) of 0.80% (0.46; 1.15). The increase was strongest among men diagnosed at a relatively early age (age<=64 years; AAPC: 1.47% (0.90; 2.05)). Mortality also increased over the study period (AAPC: 0.47% (0.10; 0.85)), whereas 5-year relative survival did not change (AAPC: 0.08% (-0.19; 0.36)). We conclude that the incidence of penile SCC has increased at a moderate and constant rate during 1956-2015, and that the most consistent increase occurred among younger men. Mortality also increased during the study period. However, survival did not change, thus changes in diagnostics and treatment had little impact on survival from penile SCC. Since a substantial proportion of penile SCC is caused by human papillomavirus (HPV), the incidence increase may in part be attributed to increased exposure to HPV in the population.