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BACKGROUND: Screening participation remains suboptimal in cervical cancer (CC) and colorectal cancer (CRC) screening despite their effectiveness in reducing cancer-related morbidity and mortality. We investigated the effectiveness of an intervention by leveraging the high participation rate in breast cancer (BC) screening as an opportunity to offer self-sampling kits to nonparticipants in CC and CRC screening. METHODS AND FINDINGS: A pragmatic, unblinded, cluster-randomised, multiple period, crossover trial was conducted in 5 BC screening units in the Central Denmark Region (CDR) between September 1, 2021 and May 25, 2022. On each of 100 selected weekdays, 1 BC screening unit was randomly allocated as the intervention unit while the remaining units served as controls. Women aged 50 to 69 years attending BC screening at the intervention unit were offered administrative check-up on their CC screening status (ages 50 to 64 years) and CRC screening status (aged 50 to 69), and women with overdue screening were offered self-sampling. Women in the control group received only standard screening offers according to the organised programmes. The primary outcomes were differences between the intervention group and the control group in the total screening coverage for the 2 programmes and in screening participation among women with overdue screening, measured 6 months after the intervention. These were assessed using intention-to-treat analysis, reporting risk differences with 95% confidence intervals (CIs). A total of 27,116 women were included in the trial, with 5,618 (20.7%) in the intervention group and 21,498 (79.3%) in the control group. Six months after the intervention, total coverage was higher in the intervention group as compared with the control group in CC screening (88.3 versus 83.5, difference 4.8 percentage points, 95% CI [3.6, 6.0]; p < 0.001) and in CRC screening (79.8 versus 76.0, difference 3.8 percentage points, 95% CI [2.6, 5.1]; p < 0.001). Among women overdue with CC screening, participation in the intervention group was 32.0% compared with 6.1% in the control group (difference 25.8 percentage points, 95% CI [22.0, 29.6]; p < 0.001). In CRC screening, participation among women overdue with screening in the intervention group was 23.8% compared with 8.9% in the control group (difference 14.9 percentage points, 95% CI [12.3, 17.5]; p < 0.001). Women who did not participate in BC screening were not included in this study. CONCLUSIONS: Offering self-sampling to women overdue with CC and CRC screening when they attend BC screening was a feasible intervention, resulting in an increase in participation and total coverage. Other interventions are required to reach women who are not participating in BC screening. TRIAL REGISTRATION: ClinicalTrials.gov NCT05022511. The record of processing activities for research projects in the Central Denmark Region (R. No.: 1-16-02-217-21).
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Neoplasias de la Mama , Neoplasias Colorrectales , Estudios Cruzados , Detección Precoz del Cáncer , Neoplasias del Cuello Uterino , Humanos , Femenino , Persona de Mediana Edad , Neoplasias Colorrectales/diagnóstico , Detección Precoz del Cáncer/métodos , Neoplasias de la Mama/diagnóstico , Neoplasias del Cuello Uterino/diagnóstico , Anciano , Dinamarca , Tamizaje Masivo/métodosRESUMEN
INTRODUCTION: Colposcopy is the most important diagnostic tool to detect cervical precancerous lesions and thereby prevention of cervical cancer. Due to age-dependent changes of the cervix, colposcopy is challenging in postmenopausal women, as the majority will have a non-visible transformation zone, resulting in increased risk of missing disease, a diagnostic cone biopsy and prolonged follow-up with repeated colposcopies. This study will be among the first to investigate, if treatment with vaginal oestrogen prior to colposcopy will improve the colposcopy performance, to ensure accurate and timely diagnosis of precancerous cervical lesions among postmenopausal women. METHODS AND ANALYSIS: A randomised blinded controlled multicentre study. Enrolment will be performed at gynaecology departments in Central Denmark Region and Region of Southern Denmark. A total of 150 postmenopausal women aged ≥50 years referred for colposcopy due to abnormal cervical screening results will be randomised 1:1 to either pretreatment with vaginal application of Vagifem 30 µg or placebo once a day for 14 days prior to colposcopy. The primary outcome will be to compare the percentage of women in the two groups with a visible transformation zone at colposcopy, and biopsies representative of the transformation zone. Secondary outcomes will be the proportion of detected cervical intraepithelial neoplasia grade 2 or higher in the cervical biopsies; the proportion of diagnostics cone biopsies; the patients' report on possible side effects and compliance to the pretreatment. ETHICS AND DISSEMINATION: The study has been approved by the Central Denmark Region Committee on Biomedical Research Ethics (1-10-72-34-22), the Central Denmark Regions' Research Unit (1-16-02-72-22) and The Danish Health Authority (Danish Medicine Agency; 2022015030). The study's EudraCT number is (1-23-456; 2022-000269-42) and it is registered on www. CLINICALTRIALS: gov. The local Good Clinical Practice (GCP) unit will supervise and monitor the study closely before, during and after the study period. Findings will be disseminated in peer-reviewed scientific journals and presented in relevant conferences. TRIAL REGISTRATION NUMBER: NCT05283421.
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Colposcopía , Posmenopausia , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Humanos , Femenino , Colposcopía/métodos , Displasia del Cuello del Útero/diagnóstico , Displasia del Cuello del Útero/patología , Persona de Mediana Edad , Administración Intravaginal , Neoplasias del Cuello Uterino/diagnóstico , Estrógenos/administración & dosificación , Dinamarca , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Multicéntricos como Asunto , Detección Precoz del Cáncer/métodosRESUMEN
BACKGROUND: Ethnic minority women are less likely to participate in cervical cancer uteri (CCU) screening compared to native women. Human Papillomavirus (HPV) self-sampling kits for CCU screening may be a potential strategy to increase participation. This study aimed to explore views and attitudes on four different types of self-sampling kits (two brushes, a first-void urine device, and a menstrual blood device) among non-Western ethnic minority women living in Denmark. METHODS: The study was a social science single case study based on focus group interviews with 30 women aged 32-54 with non-Western background from a deprived area. A phenomenological approach was applied to describe the phenomenon "self-sampling" as seen from the women's lifeworlds. The interviews were transcribed verbatim and analysed using systematic text condensation. RESULTS: The women expressed significant interest in the possibility of using HPV self-sampling kits as an alternative to being screened by their general practitioner. They were particularly motivated to use the non-invasive self-sampling kits for CCU screening as they were deemed suitable for addressing cultural beliefs related to their bodies and virginity. The women expressed interest in the use of the invasive self-sampling kits but were cautious, primarily due to lack of confidence in correctly performing self-sampling with a brush and due to cultural beliefs. CONCLUSION: The use of non-invasive self-sampling kits, such as a first-void urine collection device and menstrual blood pad, represents a promising solution to overcome cultural barriers and promote greater equality in CCU screening participation among non-Western ethnic minority women.
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BACKGROUND: High-risk human papillomavirus (HPV) test is replacing cytology as the primary cervical cancer screening test due to superior sensitivity, but in most countries women ≥65 years have never had an HPV test despite they account for around 50% of cervical cancer deaths. We explored the effect of a catch-up HPV test among 65- to 69-year-old women without previous record of HPV-based screening. METHODS AND FINDINGS: This population-based nonrandomized intervention study (quasi-experimental design) included Danish women aged 65 to 69 with no record of cervical cancer screening in the last ≥5.5 years and no HPV-exit test at age 60 to 64 at the time of study inclusion. Eligible women residing in the Central Denmark Region were invited for HPV screening either by attending clinician-based sampling or requesting a vaginal self-sampling kit (intervention group, n = 11,192). Women residing in the remaining four Danish regions received standard care which was the opportunity to have a cervical cytology collected for whatever reason (reference group, n = 33,387). Main outcome measures were detection of cervical intraepithelial neoplasia (CIN) grade 2 or worse (CIN2+) per 1,000 women eligible for the screening offer and the benefit-harm ratio of the intervention and standard practice measured as the number of colposcopies needed to detect one CIN2+ case. The minimum follow-up time was 13 months for all tested women (range: 13 to 25 months). In the intervention group, 6,965 (62.2%) were screened within 12 months from the date of study inclusion and 743 (2.2%) women had a cervical cytology collected in the reference group. The CIN2+ detection was significantly higher in the intervention group (3.9, 95% confidence interval (CI): [2.9, 5.3]; p < 0.001; n = 44/11,192) as compared to the reference group (0.3, 95% CI: [0.2, 0.6]; n = 11/33,387). For the benefit-harm ratio, 11.6 (95% CI: [8.5, 15.8]; p = 0.69; n = 511/44) colposcopies were performed to detect one CIN2+ in the intervention group as compared to 10.1 (95% CI: [5.4, 18.8]; n = 111/11) colposcopies in the reference group. The study design entails a risk of confounding due to the lack of randomization. CONCLUSIONS: The higher CIN2+ detection per 1,000 eligible women in the intervention group supports that a catch-up HPV test could potentially improve cervical cancer prevention in older women. This study informs the current scientific debate as to whether women aged 65 and above should be offered a catch-up HPV test if they never had an HPV test. TRIAL REGISTRATION: ClinicalTrials.gov NCT04114968.
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Infecciones por Papillomavirus , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Femenino , Humanos , Anciano , Persona de Mediana Edad , Masculino , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/prevención & control , Detección Precoz del Cáncer/métodos , Displasia del Cuello del Útero/diagnóstico , Frotis Vaginal , Tamizaje Masivo/métodos , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/prevención & control , Dinamarca/epidemiología , PapillomaviridaeRESUMEN
BACKGROUND: Cervical cancer incidence and mortality rates are high in older women in many developed countries, including Denmark. Therefore, Danish women aged 69 and older were invited for one additional human papilloma virus (HPV) based screening test in 2017. Here, we describe the clinical management and detection rate of cervical intraepithelial neoplasia grade 2 or worse (CIN2 +) in screen-positive women referred for colposcopy. METHODS: We conducted an observational study in public gynecology departments in Central Denmark Region, Denmark. Women were eligible for enrolment if they were aged 69 + in 2017, HPV positive on a screening test taken between April 20th, 2017, and December 31st, 2017, and had been referred for direct colposcopy. Data on participants' characteristics, colposcopic findings, and histological outcomes were collected from medical records and the Danish Pathology Databank. We estimated the proportion of women with CIN2 + at the first colposcopy visit and at end of follow up including 95% confidence intervals (CIs). RESULTS: A total of 191 women were included with a median age of 74 years (IQR: 71-78). Most women (74.9%) did not have a fully visible transformation zone at colposcopy. At the first visit 170 women (89.0%) had a histological sample collected, 34 of whom (20.0%, 95% CI 14.3-26.8%) had CIN2 + diagnosed, 19 had CIN3 + , and two had cervical cancer). During follow-up additional CIN2 + were detected resulting in a total of 42 women (24.4%, 95% CI: 18.2-31.5%) being diagnosed with CIN2 + , 25 with CIN3 + , and three with cervical cancer. When restricting to women with paired histologic results (i.e., biopsies and a loop electrosurgical excision procedure (LEEP) specimen), we found that CIN2 + was missed in 17.9% (95% CI 8.9-30.4%) of biopsies compared to the LEEP. CONCLUSION: Our findings suggest a potential risk of underdiagnosis in older postmenopausal women referred to colposcopy. Future studies should explore potential risk-markers for discrimination of women at increased risk of CIN2 + from those at low risk, as this would reduce risk of underdiagnosis and overtreatment.
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Infecciones por Papillomavirus , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Femenino , Humanos , Embarazo , Anciano , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/cirugía , Colposcopía , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/epidemiología , Displasia del Cuello del Útero/epidemiología , Biopsia/efectos adversos , PapillomaviridaeRESUMEN
BACKGROUND: Studies comparing self-collected vaginal samples with clinician-collected cervical samples with respect to high-risk human papillomavirus (HPV) detection and genotype agreement based on clinically validated full HPV genotype assays (e.g. the CLART HPV4S) are limited. This study compared the two types of samples using the CLART assay with respect to HPV detection and genotype agreement in a referral population. METHODS: A total of 212 women aged 30-59 years and diagnosed with atypical squamous cells of undetermined significance (ASC-US) within the Danish cervical cancer screening programme had a cervical sample taken at their general practitioner. Afterwards, the women took a vaginal sample with the Evalyn Brush device at home. The paired samples were HPV-tested with the full genotyping CLART HPV4S assay. Histological results, i.e. cervical intraepithelial neoplasia of grade 2 or worse (CIN2+) were available for 14 women with HPV-positive clinician-collected samples. RESULTS: The study found the same HPV prevalence in self-collected vaginal samples compared to clinician-collected cervical samples (19.3%, 95% CI 14.3-25.3% vs 18.4%, 95% CI 13.4-24.3%). The CLART HPV4S assay detected approximately the same number of CIN2+ cases in the self-collected vaginal samples compared to the clinician-collected cervical samples (13 vs 11 cases). Exactly the same genotypes were detected in 75% (21/28) of the HPV-positive paired samples, while at least one identical genotype was found in the remaining 25% (7/28) of the paired samples. CONCLUSIONS: The CLART HPV4S assay performed similarly well in self-collected vaginal samples as in clinician-collected cervical samples with respect to both HPV detection and genotype agreement when using the Evalyn Brush and the CLART HPV4S assay in a referral population. Although further evaluation is needed, the findings suggest that full HPV genotyping based on the CLART assay can be useful when establishing HPV genotype-specific referral strategies for women tested HPV-positive by self-sampling.
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Infecciones por Papillomavirus , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Femenino , Humanos , Genotipo , Detección Precoz del Cáncer/métodos , Cuello del Útero/patología , Displasia del Cuello del Útero/diagnóstico , Papillomaviridae/genética , Frotis Vaginal/métodos , Sensibilidad y EspecificidadRESUMEN
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.
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Neoplasias de la Mama , Neoplasias Colorrectales , Neoplasias del Cuello Uterino , Humanos , Femenino , Masculino , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/prevención & control , Detección Precoz del Cáncer , Tamizaje Masivo , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/prevención & control , Sistema de Registros , Dinamarca/epidemiología , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/prevención & controlRESUMEN
OBJECTIVE: To evaluate the clinical utility of p16/Ki67 dual-stain (DS) compared with cytology for detecting cervical intraepithelial lesion grade two or worse (CIN2+) in women with a transformation zone type 3 (TZ3). DESIGN: Cross-sectional study. SETTING: Colposcopy clinics in Central Denmark Region. POPULATION: Women aged 45 years or older referred for colposcopy because of an abnormal screening test. METHODS: All women had a cervical sample collected for cytology and DS testing and underwent large-loop excision of the transformation zone (LLETZ). MAIN OUTCOME MEASURE: Sensitivity, specificity and negative (NPV) and positive (PPV) predictive values of DS for CIN2+ detection were compared to those of cytology. RESULTS: Of 166 women eligible, 93 (56.0%) were included in the final analysis. Median age was 68 years (interquartile range [IQR] 63.4-70.5 years). Most women were postmenopausal (95.7%) and referred based on a positive human papillomavirus screening test (86.0%). Fifty-two women (55.9%) were DS-positive, 29 (55.8%) of whom had CIN2+ detected. Twenty-seven (29.0%) women had atypical squamous cells of undetermined significance or worse (ASC-US+), and CIN2+ was detected in 21 women (77.8%). DS had a higher sensitivity (96.7% versus 70.0% p = 0.021) and NPV (97.6% versus 86.4%, p = 0.018) compared with cytology for CIN2+ detection. In contrast, the specificity (63.5% versus 90.5% p < 0.001) and PPV (55.8% versus 77.8%, p = 0.001) were lower for DS compared with cytology. CONCLUSIONS: Dual stain may be a valuable risk marker to guide clinical management of women with a TZ3. The superior NPV of DS suggests that a diagnostic excision may safely be avoided in DS-negative women.
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Infecciones por Papillomavirus , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Anciano , Femenino , Humanos , Persona de Mediana Edad , Colorantes , Colposcopía , Estudios Transversales , Inhibidor p16 de la Quinasa Dependiente de Ciclina/análisis , Antígeno Ki-67/análisis , Papillomaviridae , Displasia del Cuello del Útero/patología , Frotis VaginalRESUMEN
INTRODUCTION: The participation rate is higher in breast cancer screening than in cervical cancer (CCU) and colorectal cancer (CRC) screening. In this cluster-randomised study, we aim to evaluate an intervention offering home-based CCU and CRC screening to women when attending breast cancer screening if they are overdue for CCU and/or CRC screening. METHODS AND ANALYSIS: On intervention days, one of the five breast cancer screening units in the Central Denmark Region will be randomly allocated to intervention, whereas the remaining units will serve as control. Women attending breast cancer screening in the intervention unit will be offered information regarding their CCU and CRC screening history, and, if overdue, they will be offered self-sampling screening kits. For CCU screening, women aged 50-64 years will be offered a vaginal self-sampling kit for human papillomavirus testing. For CRC screening, women aged 50-69 years will be offered a kit to obtain a faecal immunochemical test. Women attending the control units will receive only standard care.After the intervention, a survey will be sent to all women in the intervention and control group, asking about their experience while attending breast cancer screening.Primary outcomes will be difference in the coverage in CCU and CRC screening 6 months after intervention between the intervention and the control group, and difference in participation rates 6 months after intervention for those who were overdue for CCU and/or CRC screening at the time of the intervention. ETHICS AND DISSEMINATION: The project is listed in the record of processing activities for research projects in the Central Denmark Region (R. No.: 1-16-02-217-21). According to the Danish Consolidation Act on Research Ethics Review of Health Research Project, this study was not notifiable to the Committee (R. No.: 1-10-72-1-21). The findings will be disseminated in peer-reviewed scientific journals. TRIAL REGISTRATION NUMBER: NCT05022511.
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Neoplasias de la Mama , Neoplasias Colorrectales , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/prevención & control , Cuello del Útero , Neoplasias Colorrectales/diagnóstico , Detección Precoz del Cáncer/métodos , Femenino , Humanos , Tamizaje Masivo/métodos , Ensayos Clínicos Controlados Aleatorios como Asunto , Frotis VaginalRESUMEN
At present, human papillomavirus (HPV) testing is replacing morphology-based cytology as the primary tool for cervical cancer screening in several countries. However, the HPV assays approved for screening lack detection for all but one of the possibly carcinogenic HPV types and do not genotype all included HPV types. This study demonstrates the use of a targeted HPV next generation sequencing (NGS) panel to detect and genotype all 25 carcinogenic, probably carcinogenic, and possibly carcinogenic HPV types as well as the low-risk types HPV6 and HPV11. The panel was validated using a cohort of 93 paired liquid-based cytology samples (general practitioner (GP)-collected cervical samples and cervico-vaginal self-samples (SS)). Overall, the targeted panel had a sensitivity (GP = 97.7%, SS = 92.1%) and specificity (GP = 98.0%, SS = 96.4%) similar to the commercial HPV assays, Cobas® 4800 HPV DNA test (Roche) and CLART® HPV4S assay (GENOMICA). Interestingly, of the samples that tested positive with the NGS panel, three (6.4%) of the GP-collected samples and four (9.1%) of the self-samples tested positive exclusively for HPV types only included in the NGS panel. Thus, targeted HPV sequencing has great potential to improve the HPV screening programs since, as shown here, it can identify additional HPV positive cases, cases with HPV integration, variants in the HPV genome, and which HPV type is dominant in multi-infected cases.
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BACKGROUND: To reach non-participants, reluctant to undergo clinician-based cervical cancer screening and vaginal self-sampling, urine collection for high-risk human papillomavirus detection (hrHPV) may be valuable. Using two hrHPV DNA assays, we evaluated the concordance of hrHPV positivity in urine samples in comparison with vaginal self-samples and cervical cytology samples taken by the general practitioner (GP). We also studied women's acceptance of urine collection and preferences towards the different sampling procedures. METHODS: One hundred fifty paired self-collected urine and vaginal samples and GP-collected cervical cytology samples were obtained from 30 to 59-year-old women diagnosed with ASC-US within the Danish cervical cancer screening program. After undergoing cervical cytology at the GP, the women collected first-void urine and vaginal samples at home and completed a questionnaire. Each sample was hrHPV DNA tested by the GENOMICA CLART® and COBAS® 4800 assays. Concordance in hrHPV detection between sample types was determined using Kappa (k) statistics. Sensitivity and specificity of hrHPV detection in urine was calculated using cervical sampling as reference. RESULTS: With the COBAS assay, urine showed good concordance to the vaginal (k = 0.66) self-samples and cervical samples (k = 0.66) for hrHPV detection. The corresponding concordance was moderate (k = 0.59 and k = 0.47) using CLART. Compared to cervical sampling, urinary hrHPV detection had a sensitivity of 63.9% and a specificity of 96.5% using COBAS; compared with 51.6 and 92.4% for CLART. Invalid hrHPV test rates were 1.8% for COBAS and 26.9% for CLART. Urine collection was well-accepted and 42.3% of the women ranked it as the most preferred future screening procedure. CONCLUSIONS: Urine collection provides a well-accepted screening option. With COBAS, higher concordance between urine and vaginal self-sampling and cervical sampling for hrHPV detection was found compared to CLART. Urinary hrHPV detection with COBAS is feasible, but its accuracy may need to be improved before urine collection at home can be offered to non-participants reluctant to both cervical sampling and vaginal self-sampling.
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ADN Viral/genética , Tamizaje Masivo/métodos , Papillomaviridae/genética , Infecciones por Papillomavirus/diagnóstico , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Toma de Muestras de Orina/métodos , Displasia del Cuello del Útero/diagnóstico , Neoplasias del Cuello Uterino/diagnóstico , Adulto , Detección Precoz del Cáncer/métodos , Femenino , Humanos , Persona de Mediana Edad , Infecciones por Papillomavirus/orina , Infecciones por Papillomavirus/virología , Sensibilidad y Especificidad , Encuestas y Cuestionarios , Neoplasias del Cuello Uterino/orina , Neoplasias del Cuello Uterino/virología , Vagina/virología , Frotis Vaginal/métodos , Displasia del Cuello del Útero/orina , Displasia del Cuello del Útero/virologíaRESUMEN
INTRODUCTION: Cervical cancer screening ceases between the ages of 60 and 65 in most countries. Yet, a relatively high proportion of cervical cancers are diagnosed in women above the screening age. This study will evaluate if screening of women aged 65-69 years may result in increased detection of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) compared with women not invited to screening. Invited women may choose between general practitioner (GP)-based screening or cervico-vaginal self-sampling. Furthermore, the study will assess if self-sampling is superior to GP-based screening in reaching long-term unscreened women. METHODS AND ANALYSIS: This population-based non-randomised intervention study will include 10 000 women aged 65-69 years, with no record of a cervical cytology sample or screening invitation in the 5 years before inclusion. Women who have opted-out of the screening programme or have a record of hysterectomy or cervical amputation are excluded. Women residing in the Central Denmark Region (CDR) are allocated to the intervention group, while women residing in the remaining four Danish regions are allocated to the reference group. The intervention group is invited for human papillomavirus-based screening by attending routine screening at the GP or by requesting a self-sampling kit. The reference group receives standard care which is the opportunity to have a cervical cytology sample obtained at the GP or by a gynaecologist. The study started in April 2019 and will run over the next 4.5 years. The primary outcome will be the proportion of CIN2+ detected in the intervention and reference groups. In the intervention group, the proportion of long-term unscreened women attending GP-based screening or self-sampling will be compared. ETHICS AND DISSEMINATION: The study has been submitted to the Ethical Committee in the CDR which deemed that the study was not notifiable to the Committee and informed consent is therefore not required. The study is approved by the Danish Data Protection Regulation and the Danish Patient Safety Authority. Results will be disseminated in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04114968.
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Neoplasias del Cuello Uterino , Anciano , Ensayos Clínicos como Asunto , Detección Precoz del Cáncer , Femenino , Humanos , Tamizaje Masivo , Papillomaviridae , Infecciones por Papillomavirus/diagnóstico , Neoplasias del Cuello Uterino/diagnóstico , Frotis Vaginal , Displasia del Cuello del Útero/diagnósticoRESUMEN
Our aim was to investigate whether receiving a false positive (FP) cervical cytology result affected subsequent cervical cancer screening participation. This Danish nationwide register-based cohort study included 502,380 women aged 22.5-45 attending cervical cancer screening in 2012-2014 with a normal (n = 501,003) or FP (n = 1,377) cytology screening result. A FP result was defined as a cervical cytology showing high grade cytological abnormalities followed by a normal or 'Cervical Intraepithelial Neoplasia grade 1' biopsy result. Women were categorized as subsequent participants if they had a cervical cytology within 24-42 months after their last screening or surveillance test. We compared subsequent participation among women with a normal versus a FP result, using odds ratios including 95% confidence intervals. Participation was slightly higher among women with FP results than among women with normal results (71.5% vs. 69.2%, p = 0.058). After adjustment for age and screening history, women with FP results participated significantly more than women with normal results (OR: 1.19, 95% CI 1.06-1.35). Women receiving a FP result did not participate less in subsequent cervical cancer screening than women receiving a normal result. In fact, the use of opportunistic screening seemed to be increased among women receiving a FP result.
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Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/patología , Adulto , Biopsia/métodos , Estudios de Cohortes , Colposcopía/métodos , Detección Precoz del Cáncer/métodos , Reacciones Falso Positivas , Femenino , Humanos , Tamizaje Masivo/métodos , Persona de Mediana Edad , Frotis Vaginal/métodos , Adulto Joven , Displasia del Cuello del Útero/diagnóstico , Displasia del Cuello del Útero/patologíaRESUMEN
BACKGROUND: Immunocytochemical staining with p16/Ki67 has been suggested as a promising triage biomarker in cervical cancer screening. As dual staining is a subjective method, proper training may be required to ensure safe implementation in routine laboratories and reduce risk of misclassification. We determined concordance between novice evaluators and an expert, stratified by number of slides reviewed at three reading points. METHODS: The study was conducted at the Department of Pathology, Randers, Denmark. Women were eligible if they were aged ≥45, had been enrolled in one of two ongoing clinical studies, and had a dual stain slide available. Dual staining was performed using the CINtec plus assay. Slides were randomly selected from three reading points at which novice evaluators had reviewed <30, ~300, and ≥500 dual stain slides respectively. Level of concordance was estimated using Cohen's Kappa, κ. RESULTS: Of 600 eligible slides, 50 slides were selected for review as recommended by the manufacturer. Median age was 68 years (range: 58-74). Overall concordance was good (κ = 0.68, 95% confidence interval [CI]: 0.60-0.76), with an overall agreement of 84% (95% CI: 70.9%-92.8%). Concordance improved with increasing number of slides reviewed at a given reading point, from a moderate concordance (κ = 0.47, 95% CI: 0.05-0.90) after reviewing <30 slides to a good concordance (κ = 0.66, 95% CI: 0.20-0.88) and a very good concordance (κ = 0.88, 95% CI: 0.66-1.00) after reviewing ~300 and ≥500 slides, respectively. CONCLUSIONS: When interpreting dual stain slides from older women, concordance increased slightly as novice evaluators received more training and experience. Although further evaluation is warranted, these findings indicate that a significant amount of training and experience of novice evaluators may be needed to ensure accurate dual stain interpretation in this age group. Future studies should accurately describe training and experience of evaluators to enable a better comparison of concordance and diagnostic accuracy across studies. TRIAL REGISTRATION: NCT04114968 and NCT04298957.
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Personal de Laboratorio/normas , Patología , Competencia Profesional , Neoplasias del Cuello Uterino/diagnóstico , Anciano , Biomarcadores de Tumor/metabolismo , Proteínas Portadoras/metabolismo , Dinamarca , Femenino , Glicoproteínas/metabolismo , Humanos , Inmunohistoquímica/métodos , Antígeno Ki-67/metabolismo , Personal de Laboratorio/educación , Persona de Mediana Edad , Garantía de la Calidad de Atención de Salud , Neoplasias del Cuello Uterino/metabolismoRESUMEN
In Denmark, 45% of all incident cervical cancers are detected in underscreened women. High-level evidence supports, that non-participants in cervical cancer screening are better reached by HPV self-sampling than by regular physician-based screening, including increased uptake among un- or underscreened women. A high compliance to follow-up among HPV-positive self-samplers has been reported. In the new Danish cervical cancer screening guidelines, the regions are endorsed to offer HPV self-sampling to women, who are due to receive the second screening reminder, and in this manner potentially improve cervical cancer prevention.
Asunto(s)
Papillomaviridae , Infecciones por Papillomavirus , Neoplasias del Cuello Uterino , Dinamarca , Detección Precoz del Cáncer , Femenino , Humanos , Tamizaje Masivo , Autocuidado , Manejo de Especímenes , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/virología , Frotis VaginalRESUMEN
BACKGROUND: Participation in cervical cancer screening varies by socioeconomic status. The aims were to assess if offering human papilloma virus (HPV) self-sampling kits has an effect on screening participation among various socioeconomic groups and to determine if two invitation strategies for offering self-sampling influence the participation rate equally. METHODS: The study was based on registry data that were applied to data from a randomized controlled trial (n=9,791) measuring how offering HPV self-sampling affected screening participation. The women received either 1) a self-sampling kit mailed directly to their homes (directly mailed group); 2) an invitation to order the kit (opt-in group); or 3) a standard second reminder to attend regular cytology screening (control group). The participation data were linked to registries containing socioeconomic information. RESULTS: Women in the directly mailed group participated significantly more than women in the control group, regardless of their socioeconomic status, but the largest effects were observed in Western immigrants (participation difference [PD]=18.1%, 95% CI=10.2%-26.0%) and social welfare recipients (PD=15.2%, 95% CI=9.7%-20.6%). Compared with the control group, opt-in self-sampling only had an insignificant effect on participation among women who were immigrants, retired, or less educated. Western immigrants had a significantly higher increase in participation than native Danish women when kits were mailed directly compared with the opt-in strategy (PD=18.1%, 95% CI=10.2%-26.2% and PD=5.5%, 95% CI=2.9%-8.1%, respectively, P=0.01). CONCLUSION: All socioeconomic groups benefited from the directly mailed strategy in terms of higher screening participation, but Western immigrants and lower socioeconomic groups seemed to benefit the most. Immigrants and some lower socioeconomic groups only had insignificant benefits of opt-in self-sampling. The directly mailed strategy might be preferable to opt-in self-sampling because it ensures that ethnic minority groups obtain benefits of introducing HPV self-sampling in an organized cervical cancer screening program. TRIAL REGISTRATION: Current Controlled Trials NCT02680262. Registered February 10, 2016.
RESUMEN
BACKGROUND: Studies comparing self-samples and clinician-collected samples for high-risk human papillomavirus (HPV) detection using clinically validated PCR-based HPV DNA assays are limited. We measured the concordance of HPV detection between home-based self-sampling and general practitioner (GP) sampling using the Cobas 4800 HPV DNA test and studied women's accept of home-based self-sampling. METHODS: Paired GP-collected samples and cervico-vaginal self-samples were obtained from 213 women aged 30-59 years diagnosed with ASC-US within the cervical cancer screening program. After undergoing cervical cytology at their GP, the women collected a self-sample with the Evalyn Brush at home and completed a questionnaire. Both samples were HPV-tested using the Cobas 4800 test. Histology results were available for those who tested HPV positive in GP-collected samples. RESULTS: We observed good concordance for HPV detection between self-samples and GP-collected samples (κ: 0.70, 95% CI: 0.58-0.81). No underlying CIN2+ cases were missed by self-sampling. Women evaluated that self-sampling was easy (97.2%, 95% CI: 93.9-98.9%) and comfortable (94.8%, 95% CI: 90.9-97.4%). CONCLUSIONS: Home-based self-sampling using the Evalyn Brush and the Cobas 4800 test is an applicable and reliable alternative to GP-sampling.
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Pruebas de ADN del Papillomavirus Humano , Papillomaviridae/genética , Infecciones por Papillomavirus , Manejo de Especímenes , Adulto , ADN Viral/análisis , ADN Viral/genética , Femenino , Pruebas de ADN del Papillomavirus Humano/métodos , Pruebas de ADN del Papillomavirus Humano/normas , Humanos , Persona de Mediana Edad , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/virología , Manejo de Especímenes/métodos , Manejo de Especímenes/normas , Frotis Vaginal/métodos , Frotis Vaginal/normasRESUMEN
BACKGROUND: Cervical cancer screening participation remains insufficient in most countries. Our aim was to evaluate whether offering a HPV self-sampling kit, either mailed directly to the woman's home or using timely opt-in procedures for ordering the kit, increased screening participation compared with a standard second reminder. METHODS: In this randomized, controlled effectiveness trial, 9791 Danish women aged 30-64 who were due to receive the second reminder were equally randomized to either: 1) direct mailing of a second reminder and a self-sampling kit (directly mailed group); 2) mailing of a second reminder that offered a self-sampling kit to be ordered by e-mail, text message, phone, or webpage (opt-in group); or 3) mailing of a second reminder to attend regular cytology screening (control group). In an intention-to-treat analysis, we estimated the participation rate at 180 days post intervention, by returning a self-sample or attending regular cytology screening. We calculated the proportion of women with a positive HPV self-sample who attended for cervical cytology triage at the general practitioner within 90 days. RESULTS: Participation was significantly higher in the directly mailed group (38.0%) and in the opt-in group (30.9%) than in the control group (25.2%) (participation difference (PD): 12.8%, 95% CI: 10.6-15.0% and PD: 5.7%, 95% CI: 3.5-7.9%, respectively). Within 90 days, 107 women (90.7%, 95% CI: 83.9-95.3%) with a HPV-positive self-sample attended follow-up. CONCLUSIONS: Offering the opportunity of HPV self-sampling as an alternative to regular cytology screening increased participation; the direct mailing strategy was the most effective invitation strategy. A high compliance with follow-up was seen. TRIAL REGISTRATION: Current Controlled Trials NCT02680262 . Registered 10 February 2016.
Asunto(s)
Detección Precoz del Cáncer/métodos , Infecciones por Papillomavirus/complicaciones , Participación del Paciente , Servicios Postales/estadística & datos numéricos , Autocuidado , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/prevención & control , Adulto , Dinamarca/epidemiología , Femenino , Estudios de Seguimiento , Humanos , Análisis de Intención de Tratar , Persona de Mediana Edad , Papillomaviridae/aislamiento & purificación , Infecciones por Papillomavirus/virología , Prevalencia , Pronóstico , Proyectos de Investigación , Manejo de Especímenes , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/virología , Frotis Vaginal , Displasia del Cuello del Útero/diagnóstico , Displasia del Cuello del Útero/epidemiología , Displasia del Cuello del Útero/prevención & control , Displasia del Cuello del Útero/virologíaRESUMEN
BACKGROUND: Low patient satisfaction with the quality of out-of-hours primary care (OOH-PC) has been linked with several individual and organizational factors. However, findings have been ambiguous and may not apply to the Danish out-of-hours (OOH) setting in which general practitioners (GPs) perform the initial telephone triage. This study aimed to identify patient-related, GP-related and organizational factors associated with low patient satisfaction. METHODS: The study was based on data from a 1-year population-based survey of OOH-PC (LV-KOS) in the Central Denmark Region in 2010-2011. GPs on OOH duty completed an electronic questionnaire in the OOH computer system, and the registered patients received a subsequent postal questionnaire focusing on contact evaluation, waiting time, demographic characteristics and general self-perceived health. Associations were analysed using multivariable logistic regression with dissatisfaction as the dependent variable. RESULTS: The patient response rate was 50.6%. For all contact types, 82.5% of the patients were satisfied with the OOH-PC service. More patients were dissatisfied with telephone consultations than with clinic consultations or home visits (8.5% vs. 6.0% and 4.3%, respectively). Contacts assessed by the GP as 'not severe' were associated with dissatisfaction for telephone consultations and home visits. Poor general self-perceived health was associated with dissatisfaction for all contact types. Living in urban areas was associated with dissatisfaction for telephone consultations, while unacceptable waiting time was associated with dissatisfaction for all contact types. CONCLUSIONS: We found a high level of patient satisfaction with the OOH-PC service. The only factors affecting patient satisfaction across all contact types were unacceptable waiting time and poor general self-perceived health. For the other investigated factors, patient satisfaction depended on the type of contact. Generally, patients contacting for GP-assessed non-severe health problem and patients living in urban areas were more dissatisfied.
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Atención Posterior , Satisfacción del Paciente , Atención Primaria de Salud , Adolescente , Adulto , Anciano , Niño , Preescolar , Estudios Transversales , Dinamarca , Autoevaluación Diagnóstica , Femenino , Médicos Generales , Visita Domiciliaria , Humanos , Lactante , Masculino , Persona de Mediana Edad , Satisfacción del Paciente/estadística & datos numéricos , Atención Primaria de Salud/organización & administración , Encuestas y Cuestionarios , Teléfono , Adulto JovenRESUMEN
BACKGROUND: The effectiveness of cervical cancer screening programs is challenged by suboptimal participation and coverage. Offering cervico-vaginal self-sampling for human papillomavirus testing (HPV self-sampling) to non-participants can increase screening participation. However, the effect varies substantially among studies, especially depending on the approach used to offer HPV self-sampling. The present trial evaluates the effect on participation in an organized screening program of a HPV self-sampling kit mailed directly to the home of the woman or mailed to the woman's home on demand only, compared with the standard second reminder for regular screening. METHODS/DESIGN: The CHOiCE trial is a parallel, randomized, controlled, open-label trial. It will include 9327 women aged 30-64 years who are living in the Central Denmark Region and who have not participated in cervical cancer screening after an invitation and one reminder. The women will be equally randomized into three arms: 1) Directly mailed a second reminder including a HPV self-sampling kit; 2) Mailed a second reminder offering a HPV self-sampling kit, to be ordered by e-mail, text message, phone, or through a webpage; and 3) Mailed a second reminder for a practitioner-collected sample (control group). The primary outcome will be the proportion of women in the intervention groups who participate by returning their HPV self-sampling kit or have a practitioner-collected sample compared with the proportion of women who have a practitioner-collected sample in the control group at 90 and 180 days after mail out of the second reminders. Per-protocol and intention-to-treat analyses will be performed. The secondary outcome will be the proportion of women with a positive HPV self-collected sample who attend follow-up testing at 30, 60, or 90 days after mail out of the results. DISCUSSION: The CHOiCE trial will provide strong and important evidence allowing us to determine if and how HPV self-sampling can be used to increase participation in cervical cancer screening. This trial therefore has the potential to improve prevention and reduce the number of deaths caused by cervical cancer. TRIAL REGISTRATION: Current Controlled Trials NCT02680262 . Registered 10 February 2016.