Real-Time Monitoring of Results During First Year of Dutch Colorectal Cancer Screening Program and Optimization by Altering Fecal Immunochemical Test Cut-Off Levels.

BACKGROUND & AIMS: After careful pilot studies and planning, the national screening program for colorectal cancer (CRC), with biennial fecal immunochemical tests (FITs), was initiated in The Netherlands in 2014. A national information system for real-time monitoring was developed to allow for timely evaluation. Data were collected from the first year of this screening program to determine the importance of planning and monitoring for optimal screening program performance. METHODS: The national information system of the CRC screening program kept track of the number of invitations sent in 2014, FIT kits returned, and colonoscopies performed. Age-adjusted rates of participation, the number of positive test results, and positive predictive values (PPVs) for advanced neoplasia were determined weekly, quarterly, and yearly. RESULTS: In 2014, there were 741,914 persons invited for FIT; of these, 529,056 (71.3%; 95% CI, 71.2%-71.4%) participated. A few months into the program, real-time monitoring showed that rates of participation and positive test results (10.6%; 95% CI, 10.5%-10.8%) were higher than predicted and the PPV was lower (42.1%; 95% CI, 41.3%-42.9%) than predicted based on pilot studies. To reduce the burden of unnecessary colonoscopies and alleviate colonoscopy capacity, the cut-off level for a positive FIT result was increased from 15 to 47 µg Hb/g feces halfway through 2014. This adjustment decreased the percentage of positive test results to 6.7% (95% CI, 6.6%-6.8%) and increased the PPV to 49.1% (95% CI, 48.3%-49.9%). In total, the first year of the Dutch screening program resulted in the detection of 2483 cancers and 12,030 advanced adenomas. CONCLUSIONS: Close monitoring of the implementation of the Dutch national CRC screening program allowed for instant adjustment of the FIT cut-off levels to optimize program performance.

Comparing SurePath, ThinPrep, and conventional cytology as primary test method: SurePath is associated with increased CIN II+ detection rates.

PURPOSE: Within the last decade, SurePath and ThinPrep [both liquid-based cytology (LBC) tests] have replaced conventional cytology (CC) as primary test method in cervical cancer screening programs of multiple countries. The aim of our study was to examine the effect in the Dutch screening program. METHODS: All primary smears taken within this program from 2000 to 2011 were analyzed using the nationwide registry of histo- and cytopathology (PALGA) with a follow-up until March 2013. The percentage of smears classified as borderline/mildly dyskaryotic (BMD) and >BMD as well as CIN and cervical cancer detection rates were compared between SurePath and ThinPrep versus CC by logistic regression analyses (adjusted for age, screen region, socioeconomic status, and calendar time). RESULTS: We included 3,118,685 CC, 1,313,731 SurePath, and 1,584,587 ThinPrep smears. Using SurePath resulted in an increased rate of primary smears classified as >BMD [odds ratio (OR) = 1.12 (95% confidence interval (CI) 1.09-1.16)]. CIN I and II(+) detection rates increased by 14 % [OR = 1.14 (95% CI 1.08-1.20)] and 8 % [OR = 1.08 (95% CI 1.05-1.12)]. Cervical cancer detection rates were unaffected. Implementing ThinPrep did not result in major alterations of the cytological classification of smears, and it did not affect CIN detection rates. While not significant, cervical cancer detection rates were lower [OR = 0.87 (95% CI 0.75-1.01)]. CONCLUSIONS: The impact of replacing CC by LBC as primary test method depends on the type of LBC test used. Only the use of SurePath was associated with increased CIN II(+) detection, although it simultaneously increased the detection of CIN I.

Automated radiogrammetry is a feasible method for measuring bone quality and bone maturation in severely disabled children.

BACKGROUND: Children with severe neurological impairment and intellectual disability are prone to low bone quality and fractures. OBJECTIVE: We studied the feasibility of automated radiogrammetry in assessing bone quality in this specific group of children. We measured outcome of bone quality and, because these children tend to have altered skeletal maturation, we also studied bone age. MATERIALS AND METHODS: We used hand radiographs obtained in 95 children (mean age 11.4 years) presenting at outpatient paediatric clinics. We used BoneXpert software to determine bone quality, expressed as paediatric bone index and bone age. RESULTS: Regarding feasibility, we successfully obtained a paediatric bone index in 60 children (63.2%). The results on bone quality showed a mean paediatric bone index standard deviation score of -1.85, significantly lower than that of healthy peers (P < 0.0001). Almost 50% of the children had severely diminished bone quality. In 64% of the children bone age diverged more than 1 year from chronological age. This mostly concerned delayed bone maturation. CONCLUSION: Automated radiogrammetry is feasible for evaluating bone quality in children who have disabilities but not severe contractures. Bone quality in these children is severely diminished. Because bone maturation frequently deviated from chronological age, we recommend comparison to bone-age-related reference values.

The value of models in informing resource allocation in colorectal cancer screening: the case of The Netherlands.

In May 2011, the Dutch government decided to implement a national programme for colorectal cancer (CRC) screening using biennial faecal immunochemical test screening between ages 55 and 75. Decision modelling played an important role in informing this decision, as well as in the planning and implementation of the programme afterwards. In this overview, we illustrate the value of models in informing resource allocation in CRC screening using the role that decision modelling has played in the Dutch CRC screening programme as an example.

How many cervical cancer cases can potentially be prevented using a more sensitive screening test at young age?

The human papilloma virus (HPV) DNA test has higher sensitivity than cytology for cervical cancer screening. Therefore, cervical cancer cases that are missed by cytology could potentially be identified if we use primary HPV testing. Studies showed that HPV screening is the preferred primary test at age 35 and over. Given the high prevalence of harmless HPV infections, the use of HPV testing at younger age is less obvious. The number of cancers in young age is often mentioned to indicate the possible benefits of a more sensitive test. We actually estimated the proportion of those cases that is potentially preventable in The Netherlands by the use of a more sensitive screen-test at the first screening age 30, given that the more sensitive test is used at age 35 and over. We analysed the screening history of women diagnosed with cervical cancer in the period 2004 to March 2009, using data from the Dutch National Pathology Registry. Only 15-30% (two to four cases per 100,000 women) of the cases was preceded by negative cytology under age 35 and therefore could have been prevented by a more sensitive test at age 30. The lower the screening coverage and the shorter the screening interval in those screened at young age, the smaller the gain of a more sensitive test. So, as long as the current screening pattern is not changed, the majority of the cervical cancer cases at young age would still occur even when applying a more sensitive test at the younger ages.

Trends in end-of-life practices before and after the enactment of the euthanasia law in the Netherlands from 1990 to 2010: a repeated cross-sectional survey.

BACKGROUND: In 2002, the euthanasia act came into effect in the Netherlands, which was followed by a slight decrease in the euthanasia frequency. We assessed frequency and characteristics of euthanasia, physician-assisted suicide, and other end-of-life practices in 2010, and assessed trends since 1990. METHODS: In 1990, 1995, 2001, 2005, and 2010 we did nationwide studies of a stratified sample from the death registry of Statistics Netherlands, to which all deaths and causes were reported. We mailed questionnaires to physicians attending these deaths (2010: n=8496 deaths). All cases were weighted to adjust for the stratification procedure and for differences in response rates in relation to the age, sex, marital status, region of residence, and cause and place of death. FINDINGS: In 2010, of all deaths in the Netherlands, 2·8% (95% CI 2·5-3·2; 475 of 6861) were the result of euthanasia. This rate is higher than the 1·7% (1·5-1·8; 294 of 9965) in 2005, but comparable with those in 2001 and 1995. Distribution of sex, age, and diagnosis was stable between 1990 and 2010. In 2010, 77% (3136 of 4050) of all cases of euthanasia or physician-assisted suicide were reported to a review committee (80% [1933 of 2425] in 2005). Ending of life without an explicit patient request in 2010 occurred less often (0·2%; 95% CI 0·1-0·3; 13 of 6861) than in 2005, 2001, 1995, and 1990 (0·8%; 0·6-1·1; 45 of 5197). Continuous deep sedation until death occurred more frequently in 2010 (12·3% [11·6-13·1; 789 of 6861]) than in 2005 (8·2% [7·8-8·6; 521 of 9965]). Of all deaths in 2010, 0·4% (0·3-0·6; 18 of 6861) were the result of the patient's decision to stop eating and drinking to end life; in half of these cases the patient had made a euthanasia request that was not granted. INTERPRETATION: Our study provides insight in consequences of regulating euthanasia and physician-assisted suicide within the broader context of end-of-life practices. In the Netherlands the euthanasia law resulted in a relatively transparent practice. Although translating these results to other countries is not straightforward, they can inform the debate on legalisation of assisted dying in other countries. FUNDING: The Netherlands Organization for Research and Development (ZonMw).

Long-term impact of infantile short bowel syndrome on nutritional status and growth.

Short-term bowel adaptation has been documented, but data on long-term effects are scarce. The aim of the present study was to evaluate the long-term consequences of infantile short bowel syndrome (SBS). A cross-sectional assessment (2005-7) of growth, nutritional status, defecation pattern and health status in individuals with a history of infantile SBS, born between 1975 and 2002, were performed. Data were compared with reference values of healthy controls and presented as means and standard deviations or median and ranges. A total of forty subjects (sixteen male and twenty-four female; mean age 14·8 (SD 6·8) years) had received parenteral nutrition during a median of 110 (range 43-2345) d, following small bowel resection. The mean standard deviation scores (SDS) for weight for height and target height (TH) of the children were normal; mean SDS for height for age was - 0·9 (SD 1·3). The median BMI adults was 19·9 (range 17-26) kg/m2; mean SDS for height for age was - 1·0 (range - 2·5 to 1·5). Height in general was significantly shorter than TH, and 53 % of children and 78 % of adults were below TH range. Most subjects had normal body fat percentage (%BF). SDS for total body bone mineral density were generally normal. The SDS for bone mineral content (BMC) of the children were - 1·0 (SD 1·1). Mean energy intake was 91 % of the estimated average requirements. The frequencies of defecation and bowel complaints of the subjects were significantly higher than in healthy controls. In conclusion, infantile SBS results in shorter stature than was expected from their calculated TH. BMC was lower than reference values, but the subjects had normal weight for height and %BF.

Is the temporal artery thermometer a reliable instrument for detecting fever in children?

AIMS AND OBJECTIVE: We aimed to study the diagnostic accuracy of the temporal artery thermometer vs. rectal temperature in a large group of children with and without fever, aged 0-18 years. BACKGROUND: Many have studied the diagnostic accuracy of the temporal artery thermometer in children compared with a reference method, with contradictory outcomes. No studies have been carried out in a large group of children of all ages. DESIGN: Diagnostic accuracy/validation study. METHOD: Children (0-18 years) with fever (T>38·0°C) were recruited through the emergency department and children with normal temperatures through the day-care department of the Children's Hospital. All children routinely had rectal temperature recordings. Temporal artery temperature was recorded shortly after the rectal recording. The mean absolute difference in temperature, the level of agreement (intraclass correlation coefficient) and the sensitivity and specificity of detecting fever were calculated. RESULTS: A total number of 198 children (121 boys) participated, with a mean age of 5·1 (SD 4·7) years. Of those children, 81 had fever according to the rectal recording. Mean difference between temporal artery temperature and rectal temperature was -0·11 (SD 0·63)°C, with an agreement of 0·812. The sensitivity and specificity of the temporal artery thermometer for detecting fever were 67·9 and 98·3%, respectively. CONCLUSIONS: The diagnostic accuracy of the temporal artery thermometer in detecting fever in children of all ages is low. RELEVANCE TO CLINICAL PRACTICE: We do not recommend replacement of standard clinical thermometers with temporal artery thermometers.

Prevalence and clinical presentation of constipation in children with severe generalized cerebral palsy.

AIM: Our aim was to study the prevalence and characteristics of constipation in children with profound multiple disabilities, as data in this area are scarce. METHOD: A cross-sectional observational study was performed in specialized day-care centres and schools in the Netherlands. The study included 152 children (81 males, 71 females; mean age 9 y 6 mo, SD 4 y 6 mo). Intellectual disability ranged from moderate (7%) to profound (52%) in all participants who also had severe motor disabilities (83% classified at Gross Motor Function Classification System level V). We collected data on defaecation characteristics, food and fluid intake, and laxative consumption using standardized bowel diaries and interviews. Constipation was defined as (1) scybalous, pebble-like, hard stools in over a quarter of defaecations in combination with a defaecation frequency of less than three times per week during a 2-week study period; (2) large stools palpable on abdominal examination; or (3) laxative use or manual disimpaction of faeces. RESULTS: Of the studied population, 57% were constipated and 55% used laxatives, 27% of whom showed symptoms of constipation. Daily intakes of water and fibre were below the required standards in 87% and 53% of participants respectively, without a proven relation to constipation. INTERPRETATION: Constipation is a common problem in children with severe disabilities. Laxative use is high but dosing is frequently inadequate to prevent symptoms.

Epidemiology of low bone mineral density and fractures in children with severe cerebral palsy: a systematic review.

AIM: Children with severe cerebral palsy (CP) are at risk for developing low bone mineral density (BMD) and low-impact fractures. The aim of this study was to provide a systematic literature review of the epidemiology of fractures and low BMD in children with severe CP, with an emphasis on risk factors. Gross Motor Function Classification System (GMFCS) levels IV and V were criteria for severe cerebral palsy. METHOD: The literature (PubMed) was searched and eligible studies were given a level of evidence score using the Scottish Intercollegiate Guidelines Network criteria. RESULTS: Seven studies were found concerning epidemiology of fractures, 11 studies described epidemiology of low BMD, and 14 studies concerned risk factors. The methodological quality of most of these studies was poor. Five studies were considered well-conducted with low risk of confounding and bias. In these studies, the incidence of fractures in children with moderate to severe CP approached 4% per year, whereas the prevalence of low BMD in the femur was 77%. Limited ambulation, feeding difficulties, previous fractures, anticonvulsant use, and lower body fat mass were associated with low BMD z-scores. INTERPRETATION: There is only a limited amount of high-quality evidence on low BMD and fractures in children with severe CP.

Cervical cancer incidence after normal cytological sample in routine screening using SurePath, ThinPrep, and conventional cytology: population based study.

Objective To compare the cumulative incidence of cervical cancer diagnosed within 72 months after a normal screening sample between conventional cytology and liquid based cytology tests SurePath and ThinPrep.Design Retrospective population based cohort study.Setting Nationwide network and registry of histo- and cytopathology in the Netherlands (PALGA), January 2000 to March 2013.Population Women with 5 924 474 normal screening samples (23 833 123 person years).Exposure Use of SurePath or ThinPrep versus conventional cytology as screening test.Main outcome measure 72 month cumulative incidence of invasive cervical cancer after a normal screening sample for each screening test. Cox regression analyses assessed the hazard ratios, adjusted for calendar time, age, screening history, and socioeconomic status and including laboratories as random effects.Results The 72 month cumulative cancer incidence was 58.5 (95% confidence interval 54.6 to 62.7) per 100 000 normal conventional cytology samples, compared with 66.8 (56.7 to 78.7) for ThinPrep and 44.6 (37.8 to 52.6) for SurePath. Compared with conventional cytology, the hazard of invasive cancer was 19% lower (hazard ratio 0.81, 95% confidence interval 0.66 to 0.99) for SurePath, mainly caused by a 27% lower hazard (0.73, 0.57 to 0.93) of a clinically detected cancer. For ThinPrep, the hazard was on average 15% higher (hazard ratio 1.15, 0.95 to 1.38), mainly caused by a 56% higher hazard of a screen detected cancer (1.56, 1.17 to 2.08).Conclusions These findings should provoke reconsideration of the assumed similarity in sensitivity to detect progressive cervical intraepithelial neoplasia between different types of liquid based cytology and conventional cytology.

Should we use criteria or eyeballing to reject post-interruption tracings?

During the analysis of interrupter resistance (R(int))-measurements, most authors reject post-interruption tracings based on the shape of the pressure-time and flow-time curves. However, objective criteria for rejection are lacking. We aimed to formulate explicit rejection criteria that correspond to eyeballing the curve pattern (daily practice), in order to simplify the analysis. Inter-observer agreement within and between both methods was studied. Results obtained with the developed rejection criteria were compared to those of current practice (eyeballing) using 54 measurements (807 interruptions) of children with severe neurological impairment. Inter-observer agreement on rejection was similar using the criteria or eyeballing (85.6% vs. 82.8%). Using the criteria, more individual interruptions were rejected (43.4% vs. 29.8% using eyeballing), while discarding total measurements (<5 remaining interruptions) was similar (9.2% vs. 7.4% using eyeballing). Results using only the criteria for pressure-time curves were comparable to eyeballing. Outcome values were comparable between any of the used rejection methods and not rejecting at all. In this first detailed study on rejection of post-interruption tracings, explicit rejection criteria were developed. None of the rejection methods influenced the outcome value relevantly. However, rejection criteria can contribute to the standardization of the R(int) technique and simplify decision-making in daily practice.

Feasibility of bioelectrical impedance analysis in children with a severe generalized cerebral palsy.

OBJECTIVE: The need is strong for an accurate and easy-to-perform test to evaluate the nutritional state of children who have a severe generalized cerebral palsy, defined as a severe motor handicap and an intellectual disability. For that purpose, we determined the feasibility of bioelectrical impedance analysis (BIA) in these children and evaluated their nutritional state. METHODS: BIA recordings were done in 35 children who had a severe generalized cerebral palsy using a single-frequency BIA device. In addition, arm span and body weight were determined. Components of feasibility were whether the children tolerated the recording and felt comfortable and whether the recording could be performed in a reproducible way (prescribed body position and stable resistance and reactance values). All recordings were performed at specialized children's daycare centers or schools. RESULTS: One child (3%) did not tolerate the recording, whereas the remaining 34 children (71%) felt comfortable. Most children (74%) could be placed in the prescribed position, but stability of resistance values was low. Stability of resistance values was positively influenced by older age, a quiet location for the recording, feeling comfortable, and a small number of people in the room. For 29 children, we were able to calculate values for total body water and fat-free mass. Compared with age-matched reference values, these values were significantly decreased in all age groups. CONCLUSIONS: The present pilot study has demonstrated that BIA recording is a feasible nutritional assessment method in children who have severe generalized cerebral palsy. Because the test procedure was well tolerated by most children, its value for use in this specific population deserves further investigation.

Cervical Cancer Screening in Partly HPV Vaccinated Cohorts - A Cost-Effectiveness Analysis.

BACKGROUND: Vaccination against the oncogenic human papillomavirus (HPV) types 16 and 18 will reduce the prevalence of these types, thereby also reducing cervical cancer risk in unvaccinated women. This (measurable) herd effect will be limited at first, but is expected to increase over time. At a certain herd immunity level, tailoring screening to vaccination status may no longer be worth the additional effort. Moreover, uniform screening may be the only viable option. We therefore investigated at what level of herd immunity it is cost-effective to also reduce screening intensity in unvaccinated women. METHODS: We used the MISCAN-Cervix model to determine the optimal screening strategy for a pre-vaccination population and for vaccinated women (~80% decreased risk), assuming a willingness-to-pay of €50,000 per quality-adjusted life year gained. We considered HPV testing, cytology testing and co-testing and varied the start age of screening, the screening interval and the number of lifetime screens. We then calculated the incremental cost-effectiveness ratio (ICER) of screening unvaccinated women with the strategy optimized to the pre-vaccination population as compared to with the strategy optimized to vaccinated women, assuming different herd immunity levels. RESULTS: Primary HPV screening with cytology triage was the optimal strategy, with 8 lifetime screens for the pre-vaccination population and 3 for vaccinated women. The ICER of screening unvaccinated women 8 times instead of 3 was €28,085 in the absence of herd immunity. At around 50% herd immunity, the ICER reached €50,000. CONCLUSION: From a herd immunity level of 50% onwards, screening intensity based on the pre-vaccination risk level becomes cost-ineffective for unvaccinated women. Reducing the screening intensity of uniform screening may then be considered.

A population-based nested case control study on recurrent pneumonias in children with severe generalized cerebral palsy: ethical considerations of the design and representativeness of the study sample.

BACKGROUND: In children with severe generalized cerebral palsy, pneumonias are a major health issue. Malnutrition, dysphagia, gastro-oesophageal reflux, impaired respiratory function and constipation are hypothesized risk factors. Still, no data are available on the relative contribution of these possible risk factors in the described population. This paper describes the initiation of a study in 194 children with severe generalized cerebral palsy, on the prevalence and on the impact of these hypothesized risk factors of recurrent pneumonias. METHODS/DESIGN: A nested case-control design with 18 months follow-up was chosen. Dysphagia, respiratory function and constipation will be assessed at baseline, malnutrition and gastro-oesophageal reflux at the end of the follow-up. The study population consists of a representative population sample of children with severe generalized cerebral palsy. Inclusion was done through care-centres in a predefined geographical area and not through hospitals. All measurements will be done on-site which sets high demands on all measurements. If these demands were not met in "gold standard" methods, other methods were chosen. Although the inclusion period was prolonged, the desired sample size of 300 children was not met. With a consent rate of 33%, nearly 10% of all eligible children in The Netherlands are included (n = 194). The study population is subtly different from the non-participants with regard to severity of dysphagia and prevalence rates of pneumonias and gastro-oesophageal reflux. DISCUSSION: Ethical issues complicated the study design. Assessment of malnutrition and gastro-oesophageal reflux at baseline was considered unethical, since these conditions can be easily treated. Therefore, we postponed these diagnostics until the end of the follow-up. In order to include a representative sample, all eligible children in a predefined geographical area had to be contacted. To increase the consent rate, on-site measurements are of first choice, but timely inclusion is jeopardized. The initiation of this first study among children with severe neurological impairment led to specific, unexpected problems. Despite small differences between participants and non-participating children, our sample is as representative as can be expected from any population-based study and will provide important, new information to bring us further towards effective interventions to prevent pneumonias in this population.

Exploring the trend of increased cervical intraepithelial neoplasia detection rates in the Netherlands.

OBJECTIVE: Over the last decade, cervical intraepithelial neoplasia (CIN) detection has increased in the Netherlands. We investigated the underlying mechanism by quantifying the increase, and analyzing patterns of CIN and cervical cancer detection over time. METHODS: We observed annual CIN and cervical cancer detection rates (DRs) per 10,000 primary smears within the Dutch screening programme for 2000-2011. Joinpoint analyses were performed to determine changes in time trends, logistic regression analyses to assess the relative risk of calendar time on histological outcomes, adjusted for demographic factors and type of primary cytology test used. RESULTS: Trends of increased detection occurred for all CIN grades (ie. DRs increased from 17.8 to 36.1, from 21.0 to 35.5, and from 43.4 to 64.6 for CIN I, II, and III from 2003 to 2009). After adjusting for demographic factors, DRs were still 2.11 (95% confidence interval (CI): 1.95, 2.29), 1.79 (95% CI: 1.66, 1.92) and 1.59 (95% CI: 1.50, 1.67) times larger in 2009. When also adjusting for the type of cytology test, DRs were 1.90 (95% CI: 1.62, 2.22), 1.48 (95% CI: 1.22, 1.79) and 1.55 (95% CI: 1.39, 1.73) times larger. No trends in cervical cancer DRs were found. CONCLUSIONS: The implementation of liquid-based cytology contributed to the CIN increase. If some of these extra detected CIN are regressive this leads to overdiagnosis. Other factors, such as an increased cervical cancer risk, and implementation of imaging-assisted reading, could also have contributed.

Offering Self-Sampling to Non-Attendees of Organized Primary HPV Screening: When Do Harms Outweigh the Benefits?

BACKGROUND: Human papillomavirus (HPV) self-sampling might be a promising tool to increase effectiveness of primary HPV screening programs when offered to non-attendees. However, effectiveness could decrease if regular attendees "switch" to self-sampling, because self-sampling test characteristics may be inferior. We examined under which conditions the harms would outweigh the benefits. METHODS: The MISCAN-cervix model was used to estimate quality-adjusted life years (QALY) gained and costs of offering HPV self-sampling to non-attendees. We varied the relative CIN2(+) sensitivity and specificity (self-sampling vs. regular sampling), extra attendance, risk of extra attendees, and the switching percentage. RESULTS: Without switching, offering self-sampling is (cost-)effective under every studied condition. If the attendance due to self-sampling increases by ≥6 percentage points, higher primary background risk women (unscreened women who will never attend regular screening) attend and the relative CIN2(+) sensitivity and specificity are ≥0.95; it is (cost-)effective to offer self-sampling to non-attendees, even if all regular attendees switch. If the relative sensitivity decreases to 0.90 combined with either a 3 percentage points extra attendance or the absence of higher primary background risk women, QALYs are lost when more than 30% to 20% of the regular attendees switch. CONCLUSIONS: Offering self-sampling will gain health effects if the relative CIN2(+) sensitivity is ≥0.95, unscreened attendees are recruited, and the total attendance increases by ≥6 percentage points. Otherwise, switching of regular attendees may decrease the total effectiveness of the program. IMPACT: Self-sampling needs to be implemented with great care and advantages of office-based sampling need to be emphasized to prevent switching.

The estimated impact of natural immunity on the effectiveness of human papillomavirus vaccination.

BACKGROUND: Mathematical modelling is used to estimate the effectiveness of HPV vaccination. These estimates depend strongly on herd immunity and thus on naturally acquired immunity, a mechanism of which little is known. We estimated the impact of different vaccination strategies on HPV-16 and HPV-18 transmission and cervical cancer incidence in the Netherlands, considering different acquired immunity mechanisms. METHODS: We used the STDSIM microsimulation model, and considered two mechanisms for acquired immunity after infection: (I) full immunity with variable duration; (II) cumulatively decreasing susceptibility to reinfection. Girls aged 13-16 years received vaccination (94.7% efficacy for HPV-16 and 92.3% for HPV-18) during a once-off catch-up campaign with 50% coverage, followed by annual vaccination of 12-year-old girls (60% coverage). Alternative vaccination scenarios included increased coverage, including boys, and lower vaccine efficacy. RESULTS: HPV-16 incidence reduced by 64% under mechanism I and 75% under mechanism II; HPV-18 incidence reduced by 58% and 73%, respectively, and these reductions lead to 48-56% fewer cervical cancer cases. Increasing coverage can lead to over 96% reduction in HPV incidence. Vaccinating boys reduced incidence by 79-89% for HPV-16 and 83-98% for HPV-18 in women. CONCLUSIONS: Effectiveness estimates of HPV vaccination differ slightly between different acquired immunity mechanisms, yet these differences are unlikely to affect policy decisions. Offering vaccination to boys as well may be considered to further reduce cancer incidence.