Summary Background Screening for human papillomavirus (HPV) infection is more effective in reducing the incidence of cervical cancer than screening using Pap smears. Moreover, HPV testing can be done ...on a vaginal sample self-taken by a woman, which offers an opportunity to improve screening coverage. However, the clinical accuracy of HPV testing on self-samples is not well-known. We assessed whether HPV testing on self-collected samples is equivalent to HPV testing on samples collected by clinicians. Methods We identified relevant studies through a search of PubMed, Embase, and CENTRAL. Studies were eligible for inclusion if they fulfilled all of the following selection criteria: a cervical cell sample was self-collected by a woman followed by a sample taken by a clinician; a high-risk HPV test was done on the self-sample (index test) and HPV-testing or cytological interpretation was done on the specimen collected by the clinician (comparator tests); and the presence or absence of cervical intraepithelial neoplasia grade 2 (CIN2) or worse was verified by colposcopy and biopsy in all enrolled women or in women with one or more positive tests. The absolute accuracy for finding CIN2 or worse, or CIN grade 3 (CIN3) or worse of the index and comparator tests as well as the relative accuracy of the index versus the comparator tests were pooled using bivariate normal models and random effect models. Findings We included data from 36 studies, which altogether enrolled 154 556 women. The absolute accuracy varied by clinical setting. In the context of screening, HPV testing on self-samples detected, on average, 76% (95% CI 69–82) of CIN2 or worse and 84% (72–92) of CIN3 or worse. The pooled absolute specificity to exclude CIN2 or worse was 86% (83–89) and 87% (84–90) to exclude CIN3 or worse. The variation of the relative accuracy of HPV testing on self-samples compared with tests on clinician-taken samples was low across settings, enabling pooling of the relative accuracy over all studies. The pooled sensitivity of HPV testing on self-samples was lower than HPV testing on a clinician-taken sample (ratio 0·88 95% CI 0·85–0·91 for CIN2 or worse and 0·89 0·83–0·96 for CIN3 or worse). Also specificity was lower in self-samples versus clinician-taken samples (ratio 0·96 0·95–0·97 for CIN2 or worse and 0·96 0·93–0·99 for CIN3 or worse). HPV testing with signal-based assays on self-samples was less sensitive and specific than testing on clinician-based samples. By contrast, some PCR-based HPV tests generally showed similar sensitivity on both self-samples and clinician-based samples. Interpretation In screening programmes using signal-based assays, sampling by a clinician should be recommended. However, HPV testing on a self-sample can be suggested as an additional strategy to reach women not participating in the regular screening programme. Some PCR-based HPV tests could be considered for routine screening after careful piloting assessing feasibility, logistics, population compliance, and costs. Funding The 7th Framework Programme of the European Commission, the Belgian Foundation against Cancer, the International Agency for Research on Cancer, and the German Guideline Program in Oncology.
The second report on the implementation status of cancer screening in European Union (EU) was published in 2017. The report described the implementation status, protocols and organization (updated ...till 2016) and invitation coverage (for index year 2013) of breast, cervical and colorectal cancer screening in the EU. Experts in screening programme monitoring (N = 80) from the EU Member States having access to requisite information in their respective countries provided data on breast, cervical and colorectal cancer screening through online questionnaires. Data was collected for screening performed in the framework of publicly mandated programmes only. Filled in questionnaires were received from 26 Member States for all three sites and from one Member State for breast cancer only. Substantial improvement in screening implementation using population‐based approach was documented. Among the age‐eligible women, 94.7% were residents of Member States implementing or planning population‐based breast cancer screening in 2016, compared to 91.6% in 2007. The corresponding figures for cervical cancer screening were 72.3 and 51.3% in 2016 and 2007, respectively. Most significant improvement was documented for colorectal cancer screening with roll‐out ongoing or completed in 17 Member States in 2016, compared to only five in 2007. So the access to population‐based screening increased to 72.4% of the age‐eligible populations in 2016 as opposed to only 42.6% in 2007. The invitation coverage was highly variable, ranging from 0.2–111% for breast cancer, 7.6–105% for cervical cancer and 1.8–127% for colorectal cancer in the target populations. In spite of the considerable progress, much work remains to be done to achieve optimal effectiveness. Continued monitoring, regular feedbacks and periodic reporting are needed to ensure the desired impacts of the programmes.
What's new?
In 2003 the European Union (EU) Council urged member states to devote greater attention to breast, cervical, and colorectal cancer screening. The second report on progress in this regard was published in 2017. The present manuscript details implementation status, protocol, and organization of screening programs and screening invitation coverage of target populations in member states. The data show that within a decade, the proportion of eligible EU populations having access to breast, cervical, and colorectal cancer screening increased by 5.8, 11.9 and 33.6 percent respectively. Future Council recommendations may need to consider the incorporation of alternative screening strategies.
High attendance is essential to cervical cancer screening results. Attendance in the Finnish program is currently at 70%, but extensive opportunistic screening occurs beside the organized. A shift ...from opportunistic to organized screening is imperative to optimize the costs and impact of screening and minimize potential harms. We evaluated the effect of reminder letters (1st reminder) and self‐sampling test (2nd reminder) on program attendance. The study population consisted of 31,053 screening invitees in 31 Finnish municipalities. 8,284 non‐attendees after one invitation received a reminder letter and 4,536 further non‐attendees were offered a self‐sampling option. Socioeconomic factors related to participation were clarified by combining screening data to data from Statistics Finland. Reminder letters increased participation from 72.6% (95% CI 72.1, 73.1) to 79.2% (95% CI 78.8, 79.7) and self‐sampling further to 82.2% (95% CI 81.8, 82.7). Reminder letters with scheduled appointments resulted in higher increase than open invitations (10 vs. 6%). Screening of original non‐attendees increased the yield of CIN3+ lesions by 24%. Non‐attendance was associated with young age, immigrant background, lower education level and having never been married. We showed that a total attendance of well over 80% can be achieved within an organized program when the invitational protocol is carefully arranged.
What's new?
Self‐sampling for high‐risk human papillomavirus (hrHPV)‐testing facilitates access to cervical screening and can thereby increase screening attendance. Attendance in screening programs is also influenced, however, by invitation protocols, such as the use of reminder letters for nonattendees or prefixed appointments noted in invitations. The present study explored attendance in a routine screening setting in Finland, where program attendance is about 70%. The authors found that the combined use of personal invitations and reminder letters, scheduled appointments in invitations and letters, and self‐sampling tests sent to nonattendees can potentially raise total attendance to more than 80%.
Objective Earlier studies have reported increased risks of lung, kidney and brain cancers for exposure to lead. The International Agency for Research on Cancer (IARC) Working Group evaluated ...inorganic lead and its compounds probably carcinogenic to humans. This study aimed to assess the association between blood lead level in occupational exposure and risk of lung cancer. Methods The study was based on the follow-up of lung cancer incidence during 1973-2014 among 20 729 employees biologically monitored for their occupational lead exposure in 1973-1983. Duration of employment in the monitored work was assessed using records from the Finnish Centre for Pensions; and potential confounding by other occupational carcinogens using longitudinal information on the occupation in censuses and the Finnish National Job-Exposure Matrix (FINJEM). Occupation- and gender-specific prevalence of regular tobacco smoking and the socioeconomic status were also utilized in the adjustments for potential confounding. Results Positive trends were found for the elevated blood lead levels on the lung cancer risk. Among employees with the duration of employment of ≥60 months, the relative risk (RR) of lung cancer was 1.72 95% confidence interval (CI) 1.28-2.31 for mean blood lead 1.0-1.9 µmol/L and RR 2.63 (95% CI 1.71-4.05) for mean blood lead ≥2.0 µmol/L, compared with mean lead <0.5 µmol/L. The studied potential confounders did not explain the findings on the increased risk for lead exposure. Conclusions The current study lends support to the findings that exposure to lead increases lung cancer risk. Increased risks were seen already at rather low blood lead levels.
Most cervical cancer deaths in Finland occur after the termination of the national screening program, targeted at women aged 30 to 64 years. The purpose of this study was to examine the effectiveness ...of screening at age 65 in reducing cervical cancer mortality. A register-based cohort study was performed with a follow-up period between 1991 and 2014. Mortality risk ratios for incident cervical cancer cases diagnosed at age 65 or older were compared between women invited and not invited for screening. The background risk difference between the studied areas was accounted for by using a reference cohort. The relative risk of death for women invited for cervical cancer screening at the age of 65 was 0.52 (95% CI: 0.29-0.94). The relative risks for women not attending and attending to screening with respect to the uninvited were 1.28 (CI: 0.65-2.50) and 0.28 (CI: 0.13-0.59), respectively. Inviting 65-year-old women for screening has been effective in reducing cervical cancer mortality.
ObjectivesTo investigate further whether inorganic lead is a carcinogen among adults, or associated with increased blood pressure and kidney damage, via a large mortality study.MethodsWe conducted ...internal analyses via Cox regression of mortality in three cohorts of lead-exposed workers with blood lead (BL) data (USA, Finland, UK), including over 88 000 workers and over 14 000 deaths. Our exposure metric was maximum BL. We also conducted external analyses using country-specific background rates.ResultsThe combined cohort had a median BL of 26 µg/dL, a mean first-year BL test of 1990 and was 96% male. Fifty per cent had more than one BL test (mean 7). Significant (p<0.05) positive trends, using the log of each worker’s maximum BL, were found for lung cancer, chronic obstructive pulmonary disease (COPD), stroke and heart disease, while borderline significant trends (0.05≤p≤0.10) were found for bladder cancer, brain cancer and larynx cancer. Most results were consistent across all three cohorts. In external comparisons, we found significantly elevated SMRs for those with BLs>40 µg/dL; for bladder, lung and larynx cancer; and for COPD. In a small subsample of the US cohort (n=115) who were interviewed, we found no association between smoking and BL.ConclusionsWe found strong positive mortality trends, with increasing BL level, for several outcomes in internal analysis. Many of these outcomes are associated with smoking, for which we had no data. A borderline trend was found for brain cancer, not associated with smoking.
High coverage and attendance is essential for cervical cancer screening success. We investigated whether the previous positive experiences on increasing screening attendance by self-sampling in ...Finland are sampler device dependent.
All women identified to cervical cancer screening in 2013 in 28 Finnish municipalities were randomised to receive a lavage- (n = 6030) or a brush type of self-sampling device (n = 6045) in case of non-attendance after two invitation letters. Seven hundred seventy non-attending women in the lavage device group and 734 in the brush group received the self-sampling offer. Women's experiences were enquired with an enclosed questionnaire.
Total attendance in the lavage group increased from 71.0 to 77.7% by reminder letters and further to 80.5% by self-sampling. Respective increase in the brush group was from 72.2 to 78.6% and then to 81.5%. The participation by self-sampling was 21.7% (95% CI 18.8-24.6) in the lavage group and 23.8% (95% CI 20.8-26.9) in the brush group. Women's self-sampling experiences were mainly positive and the sampler devices were equally well accepted by the women.
Our study shows that the lavage device and brush device perform similarly in terms of uptake by non-attending women and user comfort. If self-sampling is integrated to the routine screening program in Finland, either of the devices can be chosen without the fear of losing participants due to a less acceptable device.
In many countries with organized cervical cancer screening, opportunistic Pap and human papillomavirus (HPV) tests are common. However, little is known about their effectiveness. We examined the ...effect of testing in and outside the Finnish screening program on the risk of cervical cancer. We conducted a case-control study that involved 1677 cases with invasive cervical cancer that were diagnosed between 2010 and 2019. Five- and three-year test intervals were analyzed across all ages, by age group and by cancer morphology subtype. Conditional logistic regression was used, adjusting for socioeconomic variables. Women undergoing any kind of cervical test had a significantly lowered risk of cervical cancer (adjusted OR = 0.43, 95% CI = 0.38–0.48, tests in five-year intervals). The results were similar, regardless of whether the test had been taken in the screening program or outside of it, or whether the interval was five years or three years. Testing of women at ages 35–64 showed the strongest effects, but moderate preventive effects were seen until age 79. No significant effect was seen below age 30. Tests in and outside the program were effective at the screening target age. However, participation in the program should be encouraged for optimal cost-effectiveness. Preventive effects were also seen above the program target ages.
The authors report that the labels indicating the symptom types and no symptom lines in the original version of Figure 2 were missing. The correct version of Figure 2 with the labels included is ...provided below.
Background
All‐cause mortality has been suggested as an end‐point in cancer screening trials in order to avoid biases in attributing the cause of death. The aim of this study was to investigate which ...sample size and follow‐up is needed to find a significant reduction in all‐cause mortality.
Methods
A literature review was conducted to identify previous studies that modeled the effect of screening on all‐cause mortality. Microsimulation modeling was used to simulate breast cancer, lung cancer, and colorectal cancer screening trials. Model outputs were: cancer‐specific deaths, all‐cause deaths, and life‐years gained per year of follow‐up.
Results
There were large differences between the evaluated cancers. For lung cancer, when 40 000 high‐risk people are randomized to each arm, a significant reduction in all‐cause mortality could be expected between 11 and 13 years of follow‐up. For breast cancer, a significant reduction could be found between 16 and 26 years of follow‐up for a sample size of over 300 000 women in each arm. For colorectal cancer, 600 000 persons in each arm were required to be followed for 15‐20 years. Our systematic literature review identified seven papers, which showed highly similar results to our estimates.
Conclusion
Cancer screening trials are able to demonstrate a significant reduction in all‐cause mortality due to screening, but require very large sample sizes. Depending on the cancer, 40 000‐600 000 participants per arm are needed to demonstrate a significant reduction. The reduction in all‐cause mortality can only be detected between specific years of follow‐up, more limited than the timeframe to detect a reduction in cancer‐specific mortality.
Cancer screening trials are only able to demonstrate a statistically significant difference in all‐cause mortality when 40 000‐600 000 participants per arm are participating. In addition, this significant difference can only be observed between a limited period of follow‐up.
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