C. A. Aitken

The impact of loss to follow‐up in the Dutch organised HPV‐based cervical cancer screening programme

AbstractLoss to follow‐up (LTFU) within cervical screening programmes can result in missed clinically relevant lesions, potentially reducing programme effectiveness. To examine the health impact of losing women during the screening process, we determined the proportion of women LTFU per step of the Dutch hrHPV‐based screening programme. We then determined the probability of being LTFU by age, screening history and sampling method (self‐ or clinician‐sampled) using logistic regression analysis. Finally, we estimated the number of missed CIN2+/3+ lesions per LTFU moment by using the CIN‐risk in women compliant with follow‐up. Data from the Dutch nationwide pathology databank (Palga) was used. Women eligible for screening in 2017 and 2018 were included (N = 840,428). For clinician collected (CC) samples, the highest proportion LTFU was found following ‘referral advice for colposcopy’ (5.5% after indirect referral; 3.8% after direct referral). For self‐sampling, the highest proportions LTFU were found following the advice for repeat cytology (13.6%) and after referral advice for colposcopy (8.2% after indirect referral; 4.3% after direct referral). Self‐sampling users and women with no screening history had a higher LTFU‐risk (OR: 3.87, CI: 3.55–4.23; OR: 1.39, CI: 1.20–1.61) compared to women that used CC sampling and women that have been screened before, respectively. Of all women LTFU in 2017/18, the total number of potentially missed CIN2+ was 844 (21% of women LTFU). Most lesions were missed after ‘direct referral for colposcopy’ (N = 462, 11.5% of women LTFU). So, this indicates a gap between the screening programme and clinical care which requires further attention, by improving monitoring of patients after referral.

Cost‐effectiveness of HPV‐based cervical screening based on first year results in the Netherlands: a modelling study

ObjectiveWe aim to compare the cost‐effectiveness of the old cytology programme with the new high‐risk human papillomavirus (hrHPV) screening programme, using performance indicators from the new Dutch hrHPV screening programme.DesignModel‐based cost‐effectiveness analysis.SettingThe Netherlands.PopulationDutch 30‐year‐old unvaccinated females followed up lifelong.MethodsWe updated the microsimulation screening analysis (MISCAN) model using the most recent epidemiological and screening data from the Netherlands. We simulated both screening programmes, using the screening behaviour and costs observed in each programme. Sensitivity analyses were performed on screening behaviour, utility losses and discount rates.Main outcome measuresCervical cancer incidence and mortality rates, number of screening tests and repeat tests, colposcopy referrals by lesion grade, costs from a societal perspective, quality‐adjusted life years (QALYs) gained and cost‐effectiveness.ResultsThe new Dutch cervical cancer screening programme decreased the cervical cancer mortality by 4% and the incidence by 1% compared with the old programme. Colposcopy referrals of women without cervical intra‐epithelial neoplasia grade 2 or worse, increased by 172%, but 13% more QALYs were still achieved. Total costs were reduced by 21%, mainly due to fewer screening tests. Per QALY gained, the hrHPV programme cost 46% less (€12,225) than the cytology programme (€22,678), and hrHPV‐based screening remained more cost‐effective in all sensitivity analyses.ConclusionsThe hrHPV‐based screening programme was found to be more effective and cost‐effective than the cytology programme. Alternatives for the current triage strategy should be considered to lower the number of unnecessary referrals.Tweetable abstractFirst results after implementation confirm that HPV screening is more cost‐effective than cytology screening.

Risk of Gynecologic Cancer after Atypical Glandular Cells Found on Cervical Cytology: A Population-Based Cohort Study

Abstract Background: Atypical glandular cells (AGC) are rare abnormalities found on cervical cytology associated with a range of lesions of the female reproductive system. We compared the risk of cervical and other gynecologic cancers following AGC on cervical cytology with the risk following squamous cell abnormalities of comparable severity. Methods: We used data from the Dutch Pathology Archive (PALGA) from 2000 to 2015 to categorize cervical cytology tests into groups based on most severe cytologic abnormality and correlated follow-up advice (normal cytology and “no follow-up” advice, squamous-cell–based, AGC-based, and combined AGC/squamous-cell based each with either repeat testing or referral advice). Cancer data were linked from the Netherlands Cancer Registry. Cox proportional hazard models were calculated stratified by age [younger (<50 years) and older (50+ years)], adjusted for number of previous primary cytology tests. Results: 8,537,385 cytology smears and 9,061 cancers were included. When repeat cytology testing was advised, HRs of cervical cancer (younger women: HR, 6.91; 95% CI, 5.48–8.71; older women: HR, 3.98; 95% CI, 2.38–6.66) or other gynecologic cancer diagnosis in younger women (HR, 2.82; 95% CI, 1.39–5.74) were significantly higher after an AGC-based abnormality compared with squamous-based abnormalities. Hazards were also significantly higher for “referral” advice cytology, except for cervical cancer among older women (HR, 0.88; 95% CI, 0.63–1.21). Conclusions: AGC indicates an increased risk of gynecologic cancer compared with squamous-based abnormalities of comparable severity. Impact: Gynecologists should be alert for cervical and endometrial cancers when examining women referred following AGC.

Increased Risk of High-grade Cervical Neoplasia in Women with Inflammatory Bowel Disease: A Case-controlled Cohort Study

AbstractBackground and AimsWomen with inflammatory bowel disease [IBD] may be at higher risk for cervical intraepithelial neoplasia [CIN]. However, data are conflicting. The aim of this study was to assess the risk of high-grade dysplasia and cancer [CIN2+] in IBD women and identify risk factors.MethodsClinical data from adult IBD women in a multicentre Dutch IBD prospective cohort [PSI] from 2007 onwards were linked to cervical cytology and histology records from the Dutch nationwide cytology and pathology database [PALGA], from 2000 to 2016. Patients were frequency-matched 1:4 to a general population cohort. Standardised detection rates [SDR] were calculated for CIN2+. Longitudinal data were assessed to calculate CIN2+ risk during follow-up using incidence rate ratios [IRR] and risk factors were identified in multivariable analysis.ResultsCervical records were available from 2098 IBD women [77%] and 8379 in the matched cohort; median follow-up was 13 years. CIN2+ detection rate was higher in the IBD cohort than in the matched cohort (SDR 1.27, 95% confidence interval [CI] 1.05–1.52). Women with IBD had an increased risk of CIN2+ [IRR 1.66, 95% CI 1.21–2.25] and persistent or recurrent CIN during follow-up (odds ratio [OR] 1.89, 95% CI 1.06–3.38). Risk factors for CIN2+ in IBD women were smoking and disease location (ileocolonic [L3] or upper gastrointestinal [GI] [L4]). CIN2+ risk was not associated with exposure to immunosuppressants.ConclusionsWomen with IBD are at increased risk for CIN2+ lesions. These results underline the importance of human papillomavirus [HPV] vaccination and adherence to cervical cancer screening guidelines in IBD women, regardless of exposure to immunosuppressants.

Shift in harms and benefits of cervical cancer screening in the era of HPV screening and vaccination: a modelling study

AbstractObjectiveTo calculate the changes in harms and benefits of cervical cancer screening over the first three screening rounds of the Dutch high‐risk human papillomavirus (hrHPV) screening programme.DesignMicrosimulation study.SettingDutch hrHPV screening programme; women are invited for screening every 5 or 10 years (depending on age and screening history) from age 30 to 65.PopulationPartly vaccinated population of 100 million Dutch women.MethodsMicrosimulation model MISCAN was used to estimate screening effects. Sensitivity analyses were performed on test characteristics and attendance.Main outcome measuresHarms (screening tests, unnecessary referrals, treatment‐related health problems), benefits (CIN2+ diagnoses) and programme efficiency (number needed to screen [NNS]) over the first (period 2017–2021), second (period 2022–2026) and third (period 2027–2031) rounds of hrHPV‐based screening.ResultsThe number of screening tests and CIN2+ diagnoses decreased from the first to the second round (−25.8% and −23.6%, respectively). In the third screening round, these numbers decreased further, albeit only slightly (−2.7% and −5.3%, respectively). NNS to detect a CIN2+ remained constant over the rounds; however, it increased in younger age groups while decreasing in older age groups.ConclusionBoth harms and benefits of hrHPV screening decreased over the first screening rounds. For younger women, the efficiency would decrease, whereas longer screening intervals would lead to increased efficiency in older women. Programme efficiency overall remained stable, showing the importance of longer intervals for low‐risk women.Tweetable abstract:Cervical cancer screening: both harms and benefits of hrHPV screening will decrease in the future.