Abstract
Introduction
Cervical carcinoma can be prevented by treating precancerous lesions, which are classified as low‐grade (LSIL) and high‐grade (HSIL) squamous intraepithelial lesions. Follow‐up of patients diagnosed with LSIL or treated HSIL is typically conducted in secondary care by a gynecologist. However, this may also be conducted in a primary care setting at the general practitioner. This latter approach offers potential benefits such as lower healthcare costs and care closer to home. However, the effectiveness of follow‐up by general practitioners is unknown.
Material and Methods
This retrospective cohort study included patients diagnosed with LSIL or treated HSIL by the gynecologist, with no prior history of SIL or cervical cancer, who either underwent cytological follow‐up at the gynecologist or the general practitioner. The primary outcome was loss to follow‐up at 12 months for LSIL and 24 months for treated HSIL.
Results
A total of 691 patients were followed up by the gynecologist, and 1172 by the general practitioner. In the LSIL group, 38.1% (333/874) of patients followed up by a general practitioner were lost to follow‐up at 12 months, compared with 16.6% (92/554) of those followed up by a gynecologist (p < 0.001). For treated HSIL, 44.3% (132/298) were lost to follow‐up at 24 months in the general practitioner group, versus 24.1% (33/137) in the gynecologist group (p < 0.001).
Conclusions
Follow‐up by a general practitioner after a diagnosis of LSIL or treated HSIL is associated with nearly twice the rate of loss to follow‐up compared to follow‐up by a gynecologist.
Keywords: cervical intraepithelial neoplasia, follow‐up, general practitioners, gynecology, patient compliance, primary health care, recurrence
Follow‐up by general practitioners after LSIL or treated HSIL was associated with higher loss to follow‐up rates compared with gynecologist‐led care. Loss to follow‐up was 38.1% versus 16.6% for LSIL at 12 months and 44.3% versus 24.1% for treated HSIL at 24 months.
Abbreviations
- CIN
cervical intra‐epithelial neoplasia
- HrHPV
high‐risk human papilloma virus
- HSIL
high‐grade squamous intra‐epithelial lesion
- LLETZ
large loop excision of the transformation zone
- LSIL
low‐grade squamous intra‐epithelial lesion
Key message.
Loss to follow‐up rates are higher when LSIL or treated HSIL is surveilled at the general practitioner versus at the gynecologist. Recurrence of cervical abnormalities is rare in both groups after short follow‐up. A recall system may reduce loss to follow‐up.
1. INTRODUCTION
Cervical carcinoma is the fourth most common cancer in women worldwide and a substantial contributor to cancer‐related mortality, especially in middle‐ and low income countries. 1 Cervical carcinoma can be prevented through screening, which generally involves collection of cervical material for testing on the presence of high‐risk human papillomavirus (hrHPV) and cytology to detect precancerous cervical lesions. 2 , 3 A significant decrease in the prevalence of cervical cancer following the introduction of screening programs has been observed. 4 Patients with abnormal cervical cytology have an indication for colposcopy. During colposcopy biopsies can be obtained for histological evaluation to determine presence of low‐ or high‐grade cervical disease. Cytologically, low‐grade (LSIL) and high‐grade (HSIL) squamous intraepithelial lesions classify abnormalities detected in cervical screening. Histologically, an LSIL diagnosis corresponds to CIN1 (cervical intraepithelial neoplasia), while an HSIL diagnosis includes both CIN2 and CIN3, according to the LAST Project terminology adopted in the United States. In Europe, the CIN1‐3 classification remains widely used for histological grading. 5 In the present paper, we use LSIL/HSIL terminology for both cytologically and histologically identified lesions. A diagnosis of LSIL after colposcopy is usually followed by repeated cytology and hrHPV testing for surveillance. Management of HSIL includes three options: an expectant approach with repeat cytology and hrHPV testing, a surgical approach using large loop excision of the transformation zone (LLETZ), or a pharmacological approach with imiquimod. 6 The choice of management depends on the patient's future wish to have children, given the increased risk of premature delivery following LLETZ. 7 However, for CIN3, it is recommended to perform LLETZ or initiate treatment with imiquimod. 8 , 9 Following surgical treatment, surveillance typically includes cervical cytology and hrHPV testing.
The current Dutch national guideline for precancerous cervical lesions permits surveillance by the general practitioner, instead of the gynecologist, depending on the severity of the lesion. 8 Since 2017, one hospital in the Netherlands has systematically been referring patients back to their general practitioner for surveillance with follow‐up cervical cytology and hrHPV testing, when applicable. This policy is communicated in writing to the general practitioner and both verbally and in writing to the patient. Shifting surveillance to primary care might reduce relatively expensive secondary care, strengthen regional collaboration, and ensure that general practitioners maintain their knowledge and skills. Additionally, patients face lower costs and benefit from care closer to home. However, a potential risk is that patients may be lost to follow‐up if the subsequent surveillance protocol is not properly followed. The safety of this model has not been studied before. Therefore, this study aims to evaluate the difference in loss to follow‐up among patients diagnosed with LSIL or treated for HSIL when follow‐up is provided by a general practitioner compared to a gynecologist.
2. MATERIAL AND METHODS
2.1. Study design and population
A multi‐centre cohort study was conducted in two non‐academic teaching hospitals in the Netherlands. Surveillance by the general practitioner has been implemented at one hospital since 2017. Therefore, patients were included from January 2018 till December 2020. At the other hospital, surveillance is conducted by the gynecologist.
Patients with abnormal cervical cytology (Bethesda system ≥ atypical squamous cells of undetermined significance [ASC‐US]), either detected through population‐based screening or diagnosed based on medical indication (e.g., postcoital bleeding), were referred to the gynecology departments of the including hospitals for colposcopic evaluation and, if indicated, biopsy or large loop excision of the transformation zone (LLETZ). The initial screening was performed every 5 years between the ages of 30 and 60 years by a general practitioner in case of population‐based screening, and at any age by either a general practitioner or a gynecologist in case of medical indication. Primary hrHPV testing with cytology triage was standard practice during the inclusion period in the Dutch cervical cancer screening program. 8 For women presenting with symptoms, cervical cytology was performed as part of diagnostic evaluation. Routine co‐testing with hrHPV was not standard practice according to the Dutch cervical cytology guidelines. Additional hrHPV testing could be considered on clinical indication, but this was not part of standard policy.
Inclusion criteria were a diagnosis of LSIL or HSIL treated with LLETZ. Exclusion criteria were patients under 18 years of age, a history of Human Immunodeficiency Virus (HIV), and history of LSIL, HSIL, adenocarcinoma in situ, or cervical carcinoma. Patients who were not referred back per protocol to their general practitioner on preference by the healthcare professional or patient, patients who were scheduled to return to their gynecologist but either independently opted for or were advised to receive surveillance by their general practitioner, and patients with treated HSIL who had an indication for follow‐up at 12 months due to abnormal cervical cytology at 6 months follow‐up were also excluded. Finally, patients who did not undergo follow‐up cervical cytology due to all‐cause mortality, hysterectomy, or relocation during three‐year follow‐up period were excluded.
2.2. Follow‐up
Patients with LSIL were scheduled for surveillance cytology and hrHPV testing at 12 months, and those with treated HSIL at 6 months, followed by an additional check after 24 months after treatment when the 6‐month cytology was normal. For general practitioner‐based surveillance, cervical cytology was conducted at 12 months for LSIL and at 24 months for treated HSIL when 6‐month cytology was normal. Once patients were referred back to the general practitioner for surveillance, this was communicated verbally and in writing to the patient, and in writing to the general practitioner. The letter received by the patient and the general practitioner included the results of the previous cytology, histology, and colposcopic impression, as well as the timing of the next follow‐up appointment, specified in months according to the Dutch national guideline for precancerous cervical lesions. 8 It is important to note that patients were responsible for scheduling this follow‐up appointment themselves.
2.3. Data collection
Patients were selected from the hospital files, based on the International Classification of Disease (ICD‐10) code “noninflammatory disorder of cervix uteri” and the start date of their first outpatient contact. Patients without colposcopy or LLETZ in the inclusion period, LLETZ before the inclusion period, or with a history of cervical carcinoma were excluded. All other selected patients were assessed for eligibility by reviewing their electronic patient files.
For eligible patients, characteristics such as age, smoking status, and colposcopic impression were extracted from their electronic patient files and entered into an electronic case report form in Castor Electronic Data Capture. 10 Data on cervical cytology, histology, biopsies, LLETZ, and hrHPV test results were retrieved from the Dutch nationwide network and registry of histo‐ and cytopathology in the Netherlands (Palga, Houten, the Netherlands), where the two data sets were linked using probabilistic matching. 11 Diagnosis of low‐grade or high‐grade disease was determined based on histology or, if histology was not available due to absence of biopsy or LLETZ, based on colposcopic impression. To ensure data reliability, a comprehensive quality check was conducted. All variables obtained from both the electronic patient records and the Dutch nationwide pathology database were manually reviewed and cross‐checked for consistency.
The data obtained from Palga are subject to strict access regulations. The participant data cannot be shared publicly. Researchers interested in accessing these data may submit a request directly to Palga, in accordance with their procedures (https://www.palga.nl/onderzoek). Proposals requesting access should be directed to Palga, the Dutch Pathology Registry (application number 2023–77), for review and approval.
2.4. Outcomes
The primary outcome of this study is loss to follow‐up. For cases with LSIL and treated HSIL, loss to follow‐up was defined as having no follow‐up or the first surveillance cytology occurring more than 18 and 30 months after the diagnosis, respectively. This corresponds to a 6‐month margin beyond the recommended surveillance intervals at 12 and 24 months. Sub‐analysis was conducted for each year of inclusion for patients with LSIL to account for the potential impact of the COVID‐19 pandemic.
The secondary outcome is recurrence of disease during follow‐up. Recurrence was defined as a diagnosis of LSIL or HSIL, adenocarcinoma in situ or cervical carcinoma during colposcopy or histology following abnormal surveillance cytology. Recurrence of disease was determined for patients with LSIL who were not lost to follow‐up at 18 months and 30 months for patients with treated HSIL.
2.5. Statistical analysis
For baseline characteristics and categorical variables, frequencies and corresponding percentages were calculated for both groups. The chi‐square test was used to compare loss to follow‐up rates between patients followed up by their general practitioner and those followed up by a gynecologist. The Fisher's exact test was used when the expected count was less than 5 or the observed count was less than 10. A p‐value below 0.05 was considered statistically significant. Data were analyzed using SPSS statistics for Windows (version 29, IBM Corp. 2023. Armonk, NY, USA).
3. RESULTS
3.1. Study population
A total of 3786 patients were screened for eligibility. From the 1354 patients with surveillance by the gynecologist, 139 were excluded based on registration and another 322 after reviewing the patient files (Figure 1A). This resulted in 893 eligible patients, of whom 666 were diagnosed with LSIL and 227 with HSIL. In LSIL and HSIL group, an additional 112 and 90 patients were excluded, due to follow‐up cytology not being scheduled with a gynecologist or, for HSIL, follow‐up indicated 12 months post diagnosis. As a result, 554 patients in the LSIL group and 137 patients in the HSIL group were included.
FIGURE 1.
Flowcharts of included patients: (A) Gynecologist‐based follow‐up, (B) general practitioner–based follow‐up.
Out of the 2432 patients with follow‐up performed by the general practitioner, 375 were excluded based on registration and 350 after reviewing the patient file (Figure 1B). This resulted in 1707 patients of whom 1220 were diagnosed LSIL and 487 with treated HSIL. Within the LSIL group, 346 patients were excluded due to follow‐up cytology not being scheduled with a general practitioner. This resulted in 874 patients with LSIL. In the treated HSIL group, 189 patients were excluded. This resulted in 298 patients with treated HSIL who were followed up by the general practitioner. Baseline characteristics of the included patients are presented in Table 1.
TABLE 1.
Baseline characteristics of patients with low‐ or treated high‐grade squamous intraepithelial lesions who received follow‐up care from either general practitioners or gynecologists.
| General practitioner‐based follow‐up (n = 1172) | Gynecologist‐based follow‐up (n = 691) | |||
|---|---|---|---|---|
| LSIL (n = 874 (74.6%)) | Treated HSIL (n = 298 (25.4%)) | LSIL (n = 554 (80.2%)) | Treated HSIL (n = 137 (19.8%)) | |
| Age in years | ||||
| 18–29 | 142 (16.2) | 16 (5.4) | 106 (19.1) | 10 (7.3) |
| 30–39 | 408 (46.7) | 159 (53.4) | 207 (37.4) | 74 (54.0) |
| 40–49 | 191 (21.9) | 72 (24.2) | 109 (19.7) | 35 (25.5) |
| 50–59 | 113 (12.9) | 46 (15.4) | 107 (19.3) | 12 (8.8) |
| 60+ | 20 (2.3) | 5 (1.7) | 25 (4.5) | 6 (4.4) |
| HPV status n (%) | ||||
| Positive | 841 (96.2) | 280 (94.0) | 512 (92.4) | 123 (89.8) |
| Negative | 18 (2.1) | 4 (1.3) | 17 (3.1) | 0 (0.0) |
| Unknown | 15 (1.7) | 14 (4.7) | 25 (4.5) | 14 (10.2) |
| Smoking n (%) | ||||
| Yes | 228 (26.1) | 86 (28.9) | 160 (28.9) | 50 (36.5) |
| No | 583 (66.7) | 195 (65.4) | 369 (66.6) | 82 (59.9) |
| Missing | 63 (7.2) | 17 (5.7) | 25 (4.5) | 5 (3.6) |
Abbreviations: HPV, human papilloma virus; HSIL, high‐grade squamous intraepithelial lesion; LSIL, low‐grade squamous intraepithelial lesion.
3.2. Loss to follow‐up
Among patients with LSIL, the loss to follow‐up rate at 12 months was significantly higher (38.1% (333/874)) for those who were followed up by their general practitioner compared to those followed up by the gynecologist (16.6% (92/554)). For patients with treated HSIL, the loss to follow‐up rate at 24 months was 44.3% (132/298) at the general practitioner, compared to 24.1% (33/137) for surveillance by the gynecologist (Table 2). Sub‐analysis per year showed significantly higher loss to follow‐up rates across all years for patients with LSIL and follow‐up at the general practitioner instead of the gynecologist.
TABLE 2.
Number of patients with low‐grade and high‐grade squamous intraepithelial lesions who were lost to follow‐up at the general practitioner and the gynecologist, with sub analysis by year.
| General practitioner‐based follow‐up | Gynecologist‐based follow‐up | p value | |
|---|---|---|---|
| Loss to follow‐up LSIL n/N (%) 1 | 333/874 (38.1) | 92/554 (16.6) | <0.001 |
| Loss to follow‐up LSIL 2018 n/N (%) | 138/324 (42.6) | 32/144 (22.2) | <0.001 |
| Loss to follow‐up LSIL 2019 n/N (%) | 119/284 (41.9) | 32/225 (14.2) | <0.001 |
| Loss to follow‐up LSIL 2020 n/N (%) | 76/266 (28.6) | 28/185 (15.1) | <0.001 |
| Loss to follow‐up HSIL n/N (%) | 132/298 (44.3) | 33/137 (24.1) | <0.001 |
| Gynecologist‐based follow‐up instead of general practitioner‐based | General practitioner‐based follow‐up instead of gynecologist‐based | ||
| Loss to follow‐up LSIL n/N (%) | 14/312 (4.5) | 30/103 (29.4) | <0.001 |
| Loss to follow‐up HSIL n/N (%) | 8/62 (12.9) | 4/23 (17.4) | 0.727 2 |
Note: A p‐value below 0.05 was considered statistically significant.
Abbreviations: HSIL, high‐grade squamous intraepithelial lesions; LSIL, low‐grade squamous intraepithelial lesions.
Loss to follow‐up was defined as having no follow‐up or the first surveillance cytology occurring more than 18 (LSIL) and 30 (HSIL) months after the diagnosis. This corresponds to a 6‐month margin beyond the recommended surveillance intervals.
Calculated with Fisher's exact test.
For patients who were supposed to return to their gynecologist but independently requested or were advised follow‐up care at their general practitioner, loss to follow up at 12 months was significantly higher (30/103 (29.4%)) compared to patients from the general practitioner‐based follow‐up group who had follow‐up at the gynecologist (14/312 (4.5%)). For treated HSIL, there was no significant difference between these groups in loss to follow‐up at 24 months.
3.3. Recurrence of disease
In patients with previous LSIL, recurrence of the lesion during follow‐up was observed in 1.5% (8/541) of patients followed up by their general practitioner, as compared with 2.8% (13/462) followed up by the gynecologist. Further progression to HSIL was observed in 6.7% (36/541) in the general practitioner‐based follow‐up group, compared with 3.7% (17/462) with surveillance by the gynecologist, and adenocarcinoma in situ occurred in two patients in both groups. One case of cervical carcinoma was reported in the group with gynecologist‐based follow‐up; no cases in the general practitioner‐based follow‐up group.
In patients with previously treated HSIL, recurrence of an LSIL lesion was observed in one patient in both groups. Recurrence of the HSIL lesion was observed in 0.6% (1/166) followed up by the general practitioner and 2.9% (3/104) followed up by the gynecologist. No cases of adenocarcinoma in situ or cervical carcinoma were observed.
4. DISCUSSION
The results of this study show that the rate of loss to follow‐up for general practitioner‐based follow‐up after LSIL and treated HSIL is twice as high as that for gynecologist‐based surveillance. Subgroup analyses by year show that this difference in loss to follow‐up persists across all years of inclusion. A low rate of disease recurrence was observed during follow‐up.
In 2021, only 54.8% of patients invited to participate in the Dutch national cervical screening program accepted the invitation, limiting the overall effectiveness of the program. 12 , 13 A recent study evaluating the impact of loss to follow‐up in the Dutch cervical cancer screening program showed a loss to follow‐up rate before referral for colposcopy of 4–8%. 14 This emphasizes the overall challenges of patient adherence to cervical screening.
Previous studies have consistently reported low follow‐up adherence rates among patients with abnormal cervical cytology. Srisuttayasathien and Hartz independently observed a similar loss to follow‐up rate in women with CIN1, with approximately 30% of patients failing to return for follow‐up in a hospital in Thailand and a reproductive health clinic in the United States, respectively. 15 , 16
The COVID‐19 pandemic has had a significant impact on cancer screening services globally. 17 In the Netherlands, participation in the national cervical cancer screening program, in which cervical smears are primarily performed by general practitioners, declined during the pandemic. 18 Given that routine healthcare services were disrupted by lockdown measures, it was anticipated that the pandemic might have contributed to an increased loss to follow‐up. 19 , 20 , 21 However, our year‐by‐year subanalysis found no difference in loss to follow‐up among patients requiring follow‐up during the COVID‐19 pandemic compared to those whose follow‐up was performed after the pandemic. This suggests that the pandemic may not have played a relevant role in adherence to follow‐up care in this context.
In many countries, general practitioners play a central role in cervical screening programs and follow‐up after precancerous lesions. 22 Previous studies have shown that loss to follow‐up is associated with lower socioeconomic status. 23 , 24 , 25 However, in our study population, the average socioeconomic status of the region in which patients received hospital‐based follow‐up (Eindhoven, the Netherlands) is lower compared to the region in which patients received general practitioner–based follow‐up (Breda, the Netherlands). 26 Additionally, patient costs are lower in primary care, as follow‐up by a general practitioner does not contribute to the mandatory health insurance deductible, unlike hospital‐based care. These factors suggest that socioeconomic or financial barriers are unlikely to explain the higher loss to follow‐up observed in the general practitioner–based group.
The relatively high proportion of patients lost to follow‐up after surveillance by the general practitioner in this study may be explained by the absence of a structured recall system. Patients who are referred back to their general practitioner are responsible for scheduling their own follow‐up appointments, in contrast to gynecologist‐based follow‐up, where appointments are scheduled automatically. This is supported by evidence from several studies, including experiences from Denmark, where general practitioners have been involved in follow‐up of cervical cytology for several years. 24 , 25 , 27 , 28 In Denmark, general practitioners receive electronic reminders when appropriate follow‐up was not registered. A before‐after study evaluating this approach found a reduction in loss to follow‐up. 27 These findings suggest that implementing systematic recall mechanisms at the level of general practice may be an effective strategy to enhance adherence to follow‐up care, improving the quality of cervical cancer screening.
The clinical relevance of loss to follow‐up remains uncertain. Our study shows a low recurrence rate in the group that attended follow‐up visits. However, we cannot determine whether the group that was lost to follow‐up has the same likelihood of recurrence. A study including patients with high‐grade CIN treated with LLETZ showed a recurrence of abnormal histology 2 years after treatment of 0.9% of all included patients, which is in line with our findings. 29 Additionally, previous research has estimated the median time from high‐grade CIN to cervical cancer to be 23.5 years. 30 Our study has a relatively short follow‐up period, making it difficult to determine how many patients who were lost to follow‐up have developed or will develop cervical cancer.
This study has several strengths and limitations that should be considered when interpreting the findings. This is the first study to evaluate loss to follow‐up in patients with LSIL or treated HSIL being referred back to the general practitioner for surveillance. It quantifies the extent of loss to follow‐up and explores its clinical impact, providing valuable insights for guideline developers and policymakers. Key strengths of this study include the large population screened for eligibility, resulting in a substantial number of included patients. By leveraging data from two sources, the electronic patient files and the Dutch nationwide pathology database, we enhanced data accuracy through cross‐verification, thereby improving the overall reliability of the dataset. Additionally, the data underwent rigorous quality control, ensuring that discrepancies were identified and corrected, thereby strengthening the validity of our results.
Despite the strengths of our study, it has several limitations that should be acknowledged. First, possible incomplete registration may have influenced patient selection, potentially leading to missed eligible patients and selection bias. Also, there might be differences in registration between the two centers. To mitigate this risk, we applied an identification strategy that involved ICD‐10 codes and registered diagnosis, ensuring that as many eligible patients as possible were included. A difference in exclusions due to lack of consent was observed, which can be attributed to variations in how patients were offered to opt‐out at the two centers. Another limitation is the absence of important baseline information, such as ethnicity and educational level. These variables could serve as potential confounders, as they may influence a patient's likelihood to adhere to follow‐up recommendations. 31 Finally, as patients with a history of cervical abnormalities were excluded, the generalizability of the findings is limited to populations without such a history.
Our findings may contribute to improvements in (inter)national guidelines for the surveillance of LSIL and treated HSIL. The observed loss to follow‐up highlights the need for a more structured approach for surveillance following referral back to primary care. Currently, the responsibility for follow‐up largely rests with patients, which may contribute to unintended loss to follow‐up. Implementing a recall system in primary care will most probably ensure timely and consistent follow‐up. The emergence of artificial intelligence (AI) offers additional opportunities to strengthen follow‐up strategies. AI‐based approaches could support automated recall systems, identify patterns associated with loss to follow‐up, and predict patients at higher risk of non‐adherence, thereby enabling more targeted interventions. In addition, self‐sampling for HPV testing may further enhance follow‐up in primary care settings. Self‐sampling has been shown to improve accessibility and participation, particularly among individuals less likely to attend clinician‐based follow‐up, and may therefore help reduce loss to follow‐up in cervical premalignancy screening and post‐treatment surveillance pathways. However, a current limitation is that self‐sampling is restricted to HPV testing and does not allow for cytological assessment, which may limit its applicability in follow‐up strategies requiring cytology‐based evaluation.
5. CONCLUSION
Surveillance after a diagnosis of LSIL or treated HSIL by a general practitioner is associated with twice the rate of loss to follow‐up compared to gynecologist‐based follow‐up. The clinical implications of this discrepancy remain uncertain, as disease recurrence in patients who attended follow‐up was low.
Future research could benefit from adopting a prospective design with a longer follow‐up period, allowing for data collection on key patient characteristics and experiences. This approach could facilitate adjustment for confounders and extended data on recurrence of disease. Qualitative studies using patient interviews or surveys would contribute to identifying patient opinions on follow‐up at the general practitioner's office and reasons for loss to follow‐up. A combination of quantitative and qualitative research could inform the development of tailored strategies to enhance follow‐up adherence and improve patient‐centered care.
AUTHOR CONTRIBUTIONS
Lieke van de Kam: investigation, project administration, formal analysis, data curation, writing – original draft, writing – review and editing. Albert Siebers: resources, data curation, writing – review and editing. Ruud Bekkers: conceptualization, writing – review and editing. Dennis van Hamont: funding acquisition, conceptualization, methodology, writing – review and editing, supervision. Jurgen Piek: funding acquisition, conceptualization, methodology, writing – review and editing, supervision.
FUNDING INFORMATION
This work was supported by Amphia Science Fund, Breda, The Netherlands [Grant number 2023‐1‐008]; Incentive Committee Catharina Hospital, Eindhoven, The Netherlands [Grant number 2309 – EFFECTUATE]. The funding sources had no role in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. The corresponding author had final responsibility for the decision to submit for publication.
CONFLICT OF INTEREST STATEMENT
No conflicts of interest were declared by any of the authors.
ETHICS STATEMENT
All procedures performed in this study complied with applicable laws and institutional guidelines and were approved by the Medical Research Ethics Committee United (MEC‐U) and relevant institutional review boards. The MEC‐U determined that this study was not subject to the Dutch Medical Research Involving Human Subjects Act (registration number W23.170; decision date: 16‐08‐2023). The requirement for written informed consent was waived due to the large study population and the use of anonymized data. This study was conducted in accordance with the World Medical Association Declaration of Helsinki (2013) and the European General Data Protection Regulation (GDPR). The privacy rights of all human subjects were respected throughout the study.
DATA AVAILABILITY STATEMENT
The data obtained from Palga are subject to strict access regulations. The participant data cannot be shared publicly. Researchers interested in accessing these data may submit a request directly to Palga, in accordance with their procedures (https://www.palga.nl/onderzoek). Proposals requesting access should be directed to Palga, the Dutch Pathology Registry (application number 2023‐77), for review and approval.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The data obtained from Palga are subject to strict access regulations. The participant data cannot be shared publicly. Researchers interested in accessing these data may submit a request directly to Palga, in accordance with their procedures (https://www.palga.nl/onderzoek). Proposals requesting access should be directed to Palga, the Dutch Pathology Registry (application number 2023‐77), for review and approval.