Adherence to follow-up and resource use after abnormal FIT-screening: Evaluation of the Danish colorectal cancer screening program.

Background and study aims The effectiveness of colorectal cancer screening programs depends on adherence to surveillance protocols for screening-positive individuals. We evaluated adherence in the Danish population-based screening program and estimated the volume of diagnostic resources required to achieve this adherence. Patients and methods In this register- and population-based study, we included individuals with a positive fecal immunochemical test (FIT) screening from 2014 to 2017 and followed them until mid-2022. All endoscopic, imaging, and surgical procedures performed at public and private hospitals were identified. Adherence to national protocols was reported in terms of proportions and timeliness. Use of diagnostic and surveillance procedures was estimated during a 4-year post-screening period. Results Among 82,221 individuals with a positive FIT test, 84% had a baseline colonoscopy within 1 month. After removal of intermediate or high-risk adenomas, 12% and 6%, respectively, did not have any follow-up. Only ~50% had timely surveillance. Approximately 10% to 20%, depending on their referral diagnosis, did not have a second surveillance colonoscopy. In addition, 12% with a negative colonoscopy had a second colonoscopy within 4 years. Conclusions High adherence to baseline colonoscopy after positive FIT-screening is followed by lower adherence throughout the adenoma surveillance program. Better adherence to the guidelines could potentially improve the effectiveness and efficiency of the screening program.

Predictable changes in the accuracy of human papillomavirus tests after vaccination: review with implications for performance monitoring in cervical screening.

Vaccination against human papillomavirus (HPV) is changing the performance of cytology as a cervical screening test, but its effect on HPV testing is unclear. We review the effect of HPV16/18 vaccination on the epidemiology and the detection of HPV infections and high-grade cervical lesions (CIN2+) to evaluate the likely direction of changes in HPV test accuracy. The reduction in HPV16/18 infections and cross-protection against certain non-16/18 high-risk genotypes, most notably 31, 33, and/or 45, will likely increase the test's specificity but decrease its positive predictive value (PPV) for CIN2+. Post-vaccination viral unmasking of non-16/18 genotypes due to fewer HPV16 co-infections might reduce the specificity and the PPV for CIN2+. Post-vaccination clinical unmasking exposing a higher frequency of CIN2+ related to non-16/18 high-risk genotypes is likely to increase the specificity and the PPV of HPV tests. The effect of HPV16/18 vaccination on HPV test sensitivity is difficult to predict based on these changes alone. Programmes relying on HPV detection for primary screening should monitor the frequency of false-positive and false-negative tests in vaccinated (younger) vs. unvaccinated (older) cohorts, to assess the outcomes and performance of their service.

Staged design recommendations for validating relative sensitivity of self-sample human papillomavirus tests for cervical screening.

OBJECTIVES: To ensure that the emerging methods for human papillomavirus (HPV) testing on self-collected samples in cervical screening are evaluated robustly. STUDY DESIGN AND SETTING: We assess paired study designs for relative sensitivity of self-collected vs. traditional clinician-collected samples in detection of high-grade cervical intraepithelial neoplasia. RESULTS: Designs considered are (D1) both samples at screening, with clinical actions triggered by HPV positivity; (D2) offering a self-sample test to clinician-collected HPV-positive women; (D3) as D2 but using a repeat clinician-sample as comparator; (D4) offering a choice of self- vs. clinician-sampling, and the alternative test in HPV-positive women; (D5) paired samples at referral appointment. D1 is simple to analyze but requires the largest sample size and referral of self-sample positive, clinician-sample negative women. D2 requires a much smaller sample size, and no change to clinical practice, and could be used to rule-in a test because estimates are conservative (against self-sampling). D3 mitigates this bias but requires a second clinician sample. D4 is only manageable where self-sampling already occurs. The liberal D5 might be used to rule-out a self-sampling test. CONCLUSION: A universal recommendation for an optimal study design is challenging. Staged validation might be useful with D5 as a gatekeeper for D1-D4.

Managing an extension of screening intervals: Avoiding boom and bust in health care workloads.

Extending screening intervals in ongoing cancer screening programmes can lead to challenging year-on-year variations in the number of screening tests. We explored how such variation could be diminished with a managed transition to the extended interval. We defined three extension scenarios: immediate extension for the entire target population; stepped transition by birth cohort; and gradual transition by reducing the number of available screening appointments. These were compared to a situation in which the interval remains unchanged in a demographic model covering a 15-year period. The model was populated with observed parameters from England, a real-world setting recommending cervical screening with 3-year intervals at age 25-49 and 5-year intervals at age 50-64. Informed by typical changes currently considered by several European programmes including the programme in England, we explored the effect on screening test numbers of an extension of the 3-year interval to 5 years for women younger than 50. All three extension scenarios resulted in similar cumulative numbers of screening tests, which were about 30% lower compared to a situation in which the interval would remain unchanged. However, the year-on-year variation in the number of screening tests varied between the scenarios. This variation was around 4-fold for the immediate scenario. In the stepped scenario, the yearly numbers could differ by around 20%, whereas in the gradual scenario they were virtually constant. A managed interval extension, transitioning different groups of the target population at different times, can substantially reduce the yearly variation in screening workload without increasing the total number of screening tests in the long term.

Concurrent participation in breast, cervical, and colorectal cancer screening programmes in Denmark: A nationwide registry-based study.

Women in Denmark are invited to breast, cervical, and colorectal cancer screening in their fifties and sixties. We determined the patterns of concurrent participation in the three programmes. Participation in organised cancer screening was determined using the highly complete Danish population and health care registers for all women aged 53-65 years on 31 March 2018 who continuously resided in Denmark since 1 April 2012. Data were linked using unique personal identification numbers. We studied overall and cancer-specific proportions of women undergoing screening for all three, two, one, and none of the cancers. Among all 468,507 women, 406,306 (87%) participated in breast, 345,768 (74%) in cervical, and 316,496 (68%) in colorectal cancer screening. Despite high participation, only 255,698 (55%) women were screened for all three cancers, while 123,469 (26%) were screened for two, 54,538 (12%) for one, and 34,802 (7%) were not screened for any cancer. Cancer-specific patterns were highly heterogeneous across the population but changed little after accounting for women's medical history. A significant proportion of women who are screened for a specific cancer remain unscreened for other cancers. The consistency of these data at the international level requires a reconsideration of invitational practices for organised screening.

Widening the offer of human papillomavirus self-sampling to all women eligible for cervical screening: Make haste slowly.

Self-collection of samples for human papillomavirus (HPV) testing has the potential to increase the uptake of cervical screening among underscreened women and will likely form a crucial part of the WHO's strategy to eliminate cervical cancer by 2030. In high-income countries with long-standing, organised cervical screening programmes, self-collection is increasingly becoming available as a routine offer for women regardless of their screening histories, including under- and well-screened women. For these contexts, a validated microsimulation model determined that adding self-collection to clinician collection is likely to be cost-effective on the condition that it meets specific thresholds relating to (1) uptake and (2) sensitivity for the detection of high-grade cervical intraepithelial neoplasia (CIN2+). We used these thresholds to review the 'early-adopter' programme-level evidence with a mind to determine how well and how consistently they were being met. The available evidence suggested some risk to overall programme performance in the situation where low uptake among underscreened women was accompanied by a high rate of substituting clinician sampling with self-collection among well-screened women. Risk was further compounded in a situation where the slightly reduced sensitivity of self-sampling vs clinician sampling for the detection of CIN2+ was accompanied with lack of adherence to a follow-up triage test that required a clinician sample. To support real-world programmes on their pathways toward implementation and to avoid HPV self-collection being introduced as a screening measure in good faith but with counterproductive consequences, we conclude by identifying a range of mitigations and areas worthy of research prioritisation.

Supporting the implementation of new healthcare technologies by investigating generalisability of pilot studies using area-level statistics.

BACKGROUND: Implementation of new technologies into national health care systems requires careful capacity planning. This is sometimes informed by data from pilot studies that implement the technology on a small scale in selected areas. A critical consideration when using implementation pilot studies for capacity planning in the wider system is generalisability. We studied the feasibility of using publicly available national statistics to determine the degree to which results from a pilot might generalise for non-pilot areas, using the English human papillomavirus (HPV) cervical screening pilot as an exemplar. METHODS: From a publicly available source on population indicators in England ("Public Health Profiles"), we selected seven area-level indicators associated with cervical cancer incidence, to produce a framework for post-hoc pilot generalisability analysis. We supplemented these data by those from publicly available English Office for National Statistics modules. We compared pilot to non-pilot areas, and pilot regimens (pilot areas using the previous standard of care (cytology) vs. the new screening test (HPV)). For typical process indicators that inform real-world capacity planning in cancer screening, we used standardisation to re-weight the values directly observed in the pilot, to better reflect the wider population. A non-parametric quantile bootstrap was used to calculate 95% confidence intervals (CI) for differences in area-weighted means for indicators. RESULTS: The range of area-level statistics in pilot areas covered most of the spectrum observed in the wider population. Pilot areas were on average more deprived than non-pilot areas (average index of multiple deprivation 24.8 vs. 21.3; difference: 3.4, 95% CI: 0.2-6.6). Participants in HPV pilot areas were less deprived than those in cytology pilot areas, matching area-level statistics. Differences in average values of the other six indicators were less pronounced. The observed screening process indicators showed minimal change after standardisation for deprivation. CONCLUSIONS: National statistical sources can be helpful in establishing the degree to which the types of areas outside pilot studies are represented, and the extent to which they match selected characteristics of the rest of the health care system ex-post. Our analysis lends support to extrapolation of process indicators from the HPV screening pilot across England.

A model-based analysis of the health impacts of COVID-19 disruptions to primary cervical screening by time since last screen for current and future disruptions.

We evaluated how temporary disruptions to primary cervical cancer (CC) screening services may differentially impact women due to heterogeneity in their screening history and test modality. We used three CC models to project the short- and long-term health impacts assuming an underlying primary screening frequency (i.e., 1, 3, 5, or 10 yearly) under three alternative COVID-19-related screening disruption scenarios (i.e., 1-, 2-, or 5-year delay) versus no delay in the context of both cytology-based and human papillomavirus (HPV)-based screening. Models projected a relative increase in symptomatically detected cancer cases during a 1-year delay period that was 38% higher (Policy1-Cervix), 80% higher (Harvard), and 170% higher (MISCAN-Cervix) for underscreened women whose last cytology screen was 5 years prior to the disruption period compared with guidelines-compliant women (i.e., last screen 3 years prior to disruption). Over a woman's lifetime, temporary COVID-19-related delays had less impact on lifetime risk of developing CC than screening frequency and test modality; however, CC risks increased disproportionately the longer time had elapsed since a woman's last screen at the time of the disruption. Excess risks for a given delay period were generally lower for HPV-based screeners than for cytology-based screeners. Our independent models predicted that the main drivers of CC risk were screening frequency and screening modality, and the overall impact of disruptions from the pandemic on CC outcomes may be small. However, screening disruptions disproportionately affect underscreened women, underpinning the importance of reaching such women as a critical area of focus, regardless of temporary disruptions.

Health impacts of COVID-19 disruptions to primary cervical screening by time since last screen: A model-based analysis for current and future disruptions.

Background: We evaluated how temporary disruptions to primary cervical cancer (CC) screening services may differentially impact women due to heterogeneity in their screening history and test modality. Methods: We used three CC models to project the short- and long-term health impacts assuming an underlying primary screening frequency (i.e., 1, 3, 5, or 10 yearly) under three alternative COVID-19-related screening disruption scenarios (i.e., 1-, 2- or 5-year delay) versus no delay, in the context of both cytology-based and HPV-based screening. Results: Models projected a relative increase in symptomatically-detected cancer cases during a 1-year delay period that was 38% higher (Policy1-Cervix), 80% higher (Harvard) and 170% higher (MISCAN-Cervix) for under-screened women whose last cytology screen was 5 years prior to the disruption period compared with guidelines-compliant women (i.e., last screen three years prior to disruption). Over a woman's lifetime, temporary COVID-19-related delays had less impact on lifetime risk of developing CC than screening frequency and test modality; however, CC risks increased disproportionately the longer time had elapsed since a woman's last screen at the time of the disruption. Excess risks for a given delay period were generally lower for HPV-based screeners than for cytology-based screeners. Conclusions: Our independent models predicted that the main drivers of CC risk were screening frequency and screening modality, and the overall impact of disruptions from the pandemic on CC outcomes may be small. However, screening disruptions disproportionately affect under-screened women, underpinning the importance of reaching such women as a critical area of focus, regardless of temporary disruptions. Funding: This study was supported by funding from the National Cancer Institute (U01CA199334). The contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute. Megan A Smith receives salary support from the National Health and Medical Research Council, Australia (APP1159491) and Cancer Institute NSW (ECF181561). Matejka Rebolj is funded by Cancer Research UK (reference: C8162/A27047). James O'Mahony is funded by Ireland's Health Research Board (EIA2017054). Karen Canfell receives salary support from the National Health and Medical Research Council, Australia (APP1194679). Emily A. Burger receives salary support from the Norwegian Cancer Society.

Extension of cervical screening intervals with primary human papillomavirus testing: observational study of English screening pilot data.

OBJECTIVES: To provide updated evidence about the risk of cervical intraepithelial neoplasia grade 3 or higher (CIN3+) and cervical cancer after a negative human papillomavirus (HPV) test in primary cervical screening, by age group and test assay. DESIGN: Observational study. SETTING: Real world data from the English HPV screening pilot's first and second rounds (2013-16, follow-up to end of 2019). PARTICIPANTS: 1 341 584 women. INTERVENTIONS: Cervical screening with HPV testing or liquid based cytological testing (cytology or smear tests). Women screened with cytology were referred to colposcopy after high grade cytological abnormalities or after borderline or low grade abnormalities combined with a positive HPV triage test. Women screened with HPV testing who were positive were referred at baseline if their cytology triage test showed at least borderline abnormalities or after a retest (early recall) at 12 and 24 months if they had persistent abnormalities. MAIN OUTCOME MEASURES: Detection of CIN3+ and cervical cancer after a negative HPV test. RESULTS: For women younger than 50 years, second round detection of CIN3+ in this study was significantly lower after a negative HPV screen in the first round than after cytology testing (1.21/1000 v 4.52/1000 women screened, adjusted odds ratio 0.26, 95% confidence interval 0.23 to 0.30), as was the risk of interval cervical cancer (1.31/100 000 v 2.90/100 000 woman years, adjusted hazard ratio 0.44, 0.23 to 0.84). Risk of an incident CIN3+ detected at the second screening round in the pilot five years after a negative HPV test was even lower in women older than 50 years, than in three years in women younger than 50 years (0.57/1000 v 1.21/1000 women screened, adjusted odds ratio 0.46, 0.27 to 0.79). Women with negative HPV tests at early recall after a positive HPV screening test without cytological abnormalities had a higher detection rate of CIN3+ at the second routine recall than women who initially tested HPV negative (5.39/1000 v 1.21/1000 women screened, adjusted odds ratio 3.27, 95% confidence interval 2.21 to 4.84). Detection after a negative result on a clinically validated APTIMA mRNA HPV test was similar to that after clinically validated cobas and RealTime DNA tests (for CIN3+ at the second round 1.32/1000 v 1.14/1000 women screened, adjusted odds ratio 1.05, 0.73 to 1.50). CONCLUSIONS: These data support an extension of the screening intervals, regardless of the test assay used: to five years after a negative HPV test in women aged 25-49 years, and even longer for women aged 50 years and older. The screening interval for HPV positive women who have negative HPV tests at early recall should be kept at three years.

Cytology interpretation after a change to HPV testing in primary cervical screening: Observational study from the English pilot.

BACKGROUND: Overcalling of abnormalities has been a concern for using cytology triage after positive high-risk human papillomavirus (HPV) tests in cervical screening. METHODS: The authors studied the detection of cytological and histological abnormalities at age 24 to 64 years, using data from the English HPV pilot. The pilot compared routine implementation of primary cervical screening based on cytology (N = 931,539), where HPV test results were not available before cytology reporting, with that based on HPV testing (N = 403,269), where cytology was only required after positive HPV tests. RESULTS: Revealed HPV positivity was associated with a higher direct referral to colposcopy after any abnormality (adjusted odds ratio [ORadj ], 1.16; 95% confidence interval [CI], 1.14-1.18). Laboratories with higher direct referral referred fewer persistently HPV-positive women after early recall. The detection of high-grade cervical intraepithelial neoplasia (CIN2+) after direct referral increased with an ORadj of 1.17 (95% CI, 1.13-1.20) for informed versus uninformed cytology. Generally, the positive predictive value (PPV) of colposcopy for CIN2+ remained comparable under both conditions of interpreting cytology. In women 50 to 64 years old with high-grade dyskaryosis, however, the PPV increased from 71% to 83% after revealing HPV positivity (ORadj , 2.05; 95% CI, 1.43-2.93). CONCLUSIONS: Quality-controlled cervical screening programs can avoid inappropriate overgrading of HPV-positive cytology.

COVID-19 disruption to cervical cancer screening in England.

INTRODUCTION: In England, routine invitations for cervical screening were reduced between April 2020 and June 2020 due to the COVID-19 pandemic. We quantify the impact of COVID-19 disruptions on attendance and excess diagnoses of cervical cancer (CC). METHODS: Using Public Health England CC screening data on laboratory samples received in 2018 as a baseline we quantify the reduction in screening attendances due to the COVID-19 pandemic between April 2020 and March 2021 for women aged 25-64. We model the impact on excess CC diagnoses assuming once invitations resume 87.5% of women attend within 12 months and 12.5% delay screening for 3 or 5 years (depending on age). RESULTS: The number of samples received at laboratories was 91% lower than expected during April, 85% during May and 43% during June 2020 compared to the same period in 2018. Although on average laboratories received 12.6% more samples between August 2020 and April 2021 than over the same months in 2018, by April 2021 there was a short fall of 200,949 samples (6.4% fewer than in 2018). An excess of 41 CC (4.0 per 100,000 women with a maximum screening delay of 12 months) are predicted to occur among the estimated 1,024,794 women attending this screening round with a delay. An excess of 60 CC (41.0 per 100,000 women) are predicted to occur among the estimated 146,391 women who do not attend this screening round. CONCLUSION: Prompt restoration of cervical screening services limited the impact on excess CC diagnoses. However, in 2020 a 6.4% shortfall of screening samples was observed. Every effort should be made to reassure these women that services are open and safe to attend.

The impact of catch-up bivalent human papillomavirus vaccination on cervical screening outcomes: an observational study from the English HPV primary screening pilot.

BACKGROUND: In England, bivalent vaccination (Cervarix) against high-risk human papillomavirus (HR-HPV) genotypes 16/18 was offered in a population-based catch-up campaign in 2008-2010 to girls aged 14-17 years. These women are now entering the national cervical screening programme. We determined the impact of catch-up bivalent vaccination on their screening outcomes. METHODS: We studied the overall and genotype-specific screening outcomes in 108,138 women aged 24-25 (offered vaccination) and 26-29 years (not offered vaccination) included in the English HPV screening pilot between 2013 and 2018. RESULTS: At 24-25 years, the detection of high-grade cervical intraepithelial neoplasia (CIN2+) associated with HPV16/18 decreased from 3 to 1% (p < 0.001), with estimated vaccine effectiveness of 87% (95% CI: 82-91%). The detection of any CIN2+ halved from 6 to 3% (p < 0.001), with an estimated vaccine effectiveness of 72% (95% CI: 66-77%). The positive predictive value of a colposcopy for CIN2+ decreased for both low-grade (p < 0.001) and high-grade (p = 0.02) abnormalities on triage cytology. The decreases in screen-detected abnormalities at age 26-29 were of a substantially smaller magnitude. CONCLUSIONS: These data confirm high effectiveness of bivalent HPV vaccination delivered through a population-based catch-up campaign in England. These findings add to the rationale for extending screening intervals for vaccinated cohorts.

Adherence to follow-up after the exit cervical cancer screening test at age 60-64: A nationwide register-based study.

BACKGROUND: In Denmark, human papillomavirus (HPV) testing has replaced cytology in primary cervical cancer screening for women aged 60-64; at this age, women are invited for the last (exit) screening test within the national organized program. AIM: We investigated the adherence of these women to the recommended follow-up after a non-negative (positive or inadequate) HPV test and the overall resource use during that follow-up. MATERIALS & METHODS: We included all 2926 women aged 60-64 years with nonnegative HPV screening tests between March 2012 and December 2016. All relevant follow-up tests and procedures were retrieved until the end of 2020 from the highly complete Danish administrative health registers, and the data were linked at the individual level. We determined the extent to which the adherence patterns followed the national recommendations for follow-up and estimated the total numbers of tests and diagnostic procedures utilized during the entire process. RESULTS: In total, only 26% of women had follow-up in accordance with the recommendations; 4% had no follow-up, 46% had insufficient follow-up, and 24% had more follow-up than recommended. We estimated that 17% of women remained in follow-up for longer than 4 years. The average numbers of diagnostic tests and procedures used after positive HPV screening were higher than expected, even among women who had insufficient follow-up, that is, those who received less invasive procedures than recommended, or experienced delays in receiving those procedures. CONCLUSION: To conclude, we found that the patterns of follow-up of women with nonnegative primary HPV screening tests at 60-64 often diverged from the recommendations. Addressing these inconsistencies in follow-up by providing evidence for optimal clinical management should help improve the quality of screening programs and secure an equal and reliable follow-up care service for all women.

Acceleration of cervical cancer diagnosis with human papillomavirus testing below age 30: Observational study.

Several international cervical screening guidelines advise against using high-risk human papillomavirus (HR-HPV) testing in women younger than 30. The rationale for this in young women, lies in the potential for additional detection of both low-grade and high-grade cervical intraepithelial neoplasia (CIN) leading to unnecessary treatments without reducing the burden of cervical cancer. We studied 56 544 women screened at 24 to 29 with HR-HPV testing and 116 858 screened with liquid-based cytology (LBC) in the English HPV screening pilot. They were compared to 528 460 women screened at the age of 30 to 49. We studied the detection of cervical cancer and CIN2/3 across two consecutive screening rounds 3 years apart. At 24 to 29, a positive HR-HPV test detected more cases of cervical cancer in the prevalence round than did a positive LBC test (1.36/1000 screened vs 0.82/1000, ORadj : 1.61, 95% CI: 1.18-2.19). In women with a negative HR-HPV test, cervical cancer was diagnosed before or at the incidence round in 0.07/1000. After a negative LBC test, cancer detection reached 0.47/1000 and 40% of these cases were diagnosed at FIGO stage IB+. HR-HPV testing increased the detection of CIN2/3 diagnoses in two consecutive rounds combined by 30% (71.9/1000 vs 55.2/1000). The patterns of detection of cervical cancer and CIN2/3 were almost identical at older ages. These data support using HR-HPV testing for screening of women younger than 30, which not only accelerates the diagnosis of cervical cancer but leads to a similar relative increase in CIN2/3 diagnosis to that found in women aged 30 to 49.

Age-specific outcomes from the first round of HPV screening in unvaccinated women: Observational study from the English cervical screening pilot.

OBJECTIVE: To report detailed age-specific outcomes from the first round of an English pilot studying the implementation of high-risk human papillomavirus (HR-HPV) testing in primary cervical screening. DESIGN: Observational study with screening in 2013-2016, followed by two early recalls and/or colposcopy until the end of 2019. SETTING: Six NHS laboratory sites. POPULATION: A total of 1 341 584 women undergoing screening with HR-HPV testing or liquid-based cytology (LBC). METHODS: Early recall tests and colposcopies were recommended, depending on the nature of the screening-detected abnormality. MAIN OUTCOME MEASURES: We reported standard screening process indicators, e.g. proportions with an abnormality, including high-grade cervical intraepithelial neoplasia (CIN2+) or cancer, and the positive predictive value (PPV) of colposcopy for CIN2+, by screening test and age group. RESULTS: Among unvaccinated women screened with HR-HPV testing at age 24-29 years, 26.9% had a positive test and 10.4% were directly referred to colposcopy following cytology triage, with a PPV for CIN2+ of 47%. At 50-64 years of age, these proportions were much lower: 5.3%, 1.2% and 27%, respectively. The proportions of women testing positive for HR-HPV without cytological abnormalities, whose early recall HR-HPV tests returned negative results, were similar across the age spans: 54% at 24-29 years and 55% at 50-64 years. Two-thirds of infections at any age were linked to non-16/18 genotypes. Among women with CIN2, CIN3 or cervical cancer, however, the proportion of non-16/18 infections increased with age. As expected, the detection of abnormalities was lower following screening with LBC. CONCLUSIONS: These data provide a reliable reference for future epidemiological studies, including those concerning the effectiveness of HPV vaccination. TWEETABLE ABSTRACT: Data from the English pilot study provide a comprehensive overview of abnormalities detected through HPV screening.

Human Papillomavirus Testing in the Last Cervical Screening Round at Age 60-64 Years.

OBJECTIVE: To compare the real-life screening outcomes after cytology was replaced by human papillomavirus (HPV) testing for women aged 60-64 years. METHODS: Using the Danish national pathology register, we compared screening outcomes during two consecutive calendar periods, one where women were screened with cytology and one where most women were screened with HPV testing. Our primary outcomes were the proportions of women with positive test results, high-grade cervical intraepithelial neoplasia (CIN 2 or worse), and cervical cancer. RESULTS: Women screened during the HPV testing period were more likely to have a positive screening test result than were women screened during the cytology period (relative proportion 2.80, 95% CI 2.65-2.96). The detection of CIN 2 or worse was also increased (relative proportion 1.54, 95% CI 1.31-1.80), whereas there was no increase in screen-detected cervical cancer diagnoses (relative proportion 1.27, 95% CI 0.76-2.12). Within the first 4 years after a negative screening test result, including 168,477 woman-years at risk after a negative screen result in the HPV period and 451,421 woman-years after a negative screen result in the cytology period, the risk of a cervical cancer diagnosis was approximately 4 per 100,000 woman-years and was similar for both screening tests (relative risk 0.99, 95% CI 0.41-2.35). CONCLUSION: Human papillomavirus testing led to more positive screening test results and diagnoses of high-grade CIN lesions. Few women were diagnosed with cervical cancer after a negative screening test result.

Variations in pathways and resource use in follow-up after abnormal mammography screening: a nationwide register-based study.

PURPOSE: Mammography screening reduces breast cancer mortality, but a successful screening programme depends on both high participation and a sufficient follow-up of abnormalities. This study investigated patterns of follow-up after abnormal screening mammography in Denmark, and whether the variation was associated with health care resource use. METHODS: We included 19,458 women aged 50-69 years with an abnormal screening mammography during a 3-year period of 2014-2016. Women were followed until the end of 2018. Their follow-up pathway was categorized in terms of the timeliness, appropriateness (i.e. whether all recommended diagnostic tests were utilized), and the ratio of benign vs. malignant surgeries. Further, we estimated health care resource use including post-diagnostic imaging and surgery procedures. RESULTS: Ninety-seven percent of women had a diagnostic follow-up test within 6 months and 94% of those had diagnostic procedures in accordance with the recommendations. The proportion with timely follow-up (i.e. within 1 month) was 83%, but varied significantly between administrative regions (p < 0.001), and also between women with a screen-detected cancer and those with a false-positive mammogram (87% vs. 81%, p < 0.001). The ratio between having a benign versus a malignant surgery was 1:8, but it varied depending on which tests were used for diagnosis. The average number of procedures was, generally, in accordance with the recommendations. CONCLUSION: In most cases, follow-up after abnormal screening mammography followed national recommendations. We nevertheless found that this was not always the case in certain subgroups and administrative regions.