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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).

Asunto(s)

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/métodos

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INTRODUCTION: In Denmark, where human papillomavirus (HPV) -based cervical cancer screening is being implemented, the aim of this pilot implementation study was to test a specific screening algorithm, assess follow-up examination attendance, and measure the proportion of precancer lesions found in relation to the number of women referred for colposcopy. MATERIAL AND METHODS: From May 2017 to December 2020, 36 417 women in the uptake area of the Department of Pathology, Vejle Hospital, Region of Southern Denmark, were included in the HPV group. Women positive for HPV16/18 irrespective of cytology and women positive for other high-risk HPV (hrHPV) types having concomitant abnormal cytology were referred directly to colposcopy. Women positive for other hrHPV types and normal cytology were referred to repeat screening after 12 months, and hrHPV negative to routine screening after three years. We obtained information on screening results and subsequent histological diagnosis from the Danish Pathology Databank through September 2022. RESULTS: 3.6% of the women were referred to colposcopy after primary screening, 5% to repeat screening after 12 months, and 91.4% back to routine screening. High follow-up rates were observed: 96% attended colposcopy after primary screening, with 91% attending colposcopy after repeat screening. CIN3+ was detected at colposcopy following the primary screening in 28.1% of HPV16/18-positive women and 18.2% of those positive for other hrHPV types with concomitant abnormal cytology. Of the women with other hrHPV and simultaneous ASCUS/LSIL, 8% had CIN3+. At the repeat screening, 43% had become hrHPV negative, 55% were persistently positive for other hrHPV, and 2% had turned positive for HPV16/18. At the colposcopy following repeat screening, 10.1% of the women positive for other hrHPV were diagnosed with CIN3+, in comparison with 11.1% of the HPV16/18-positive women. CONCLUSIONS: In this pilot implementation study, an algorithm for HPV-based screening was evaluated in a Danish setting. The results demonstrated high attendance at follow-up examinations and provided insights into the number of colposcopy referrals and the detection of CIN2 and CIN3+ cases. The results suggest that women testing positive for other hrHPV in combination with ASCUS/LSIL at primary screening could potentially be referred to repeat screening instead of an immediate colposcopy.

Asunto(s)

Algoritmos , Colposcopía , Detección Precoz del Cáncer , Infecciones por Papillomavirus , Neoplasias del Cuello Uterino , Humanos , Femenino , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/virología , Dinamarca/epidemiología , Detección Precoz del Cáncer/métodos , Infecciones por Papillomavirus/diagnóstico , Adulto , Persona de Mediana Edad , Proyectos Piloto , Displasia del Cuello del Útero/diagnóstico , Displasia del Cuello del Útero/virología , Tamizaje Masivo/métodos , Anciano , Virus del Papiloma Humano

RESUMEN

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.

Asunto(s)

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/métodos

RESUMEN

INTRODUCTION: The objective of the study was to provide a comprehensive description of perioperative morbidity associated with robot-assisted surgery (RAS) in a gynecological oncology setting in order to improve the preoperative counseling of women and support shared decision-making. MATERIAL AND METHODS: All women scheduled for intended RAS between January 2015 and December 2022 were prospectively included in an electronic morbidity database for the analyses of perioperative complications. RESULTS: In total, 2225 women were included. Sixty-four patients (2.9%) experienced an intraoperative complication. Intraoperative complications were associated with a higher rate of conversion to laparotomy (15.6% vs. 1.8%, p < 0.001), a higher rate of major postoperative morbidity (9.3% vs. 2.4%, p < 0.001), and a higher rate of reoperation (9.3% vs. 1.7%, p < 0.001), compared to cases without intraoperative complications. Thirty-day postoperative morbidity was evaluated according to the Memorial Sloan-Kettering Cancer Center Surgical Secondary Events Grading System. Grade 3-5 events were considered major. A total of 57 patients (2.6%) experienced a major event after surgery, postoperative rupture of the vaginal vault being the most common complication requiring surgical intervention. Conversion to laparotomy occurred in 49 cases (2.2%) and was associated with higher intraoperative blood loss (300 mL vs. 25 mL, p < 0.001), a higher rate of postoperative major events (20.4% vs. 2.2%, p < 0.001), and a higher rate of reoperation (11.8% vs. 1.6%, p < 0.001). CONCLUSIONS: Our study demonstrates low rates of major perioperative morbidity and conversion to laparotomy after RAS performed by trained high-volume surgeons in a gynecological oncology setting.

Asunto(s)

Neoplasias de los Genitales Femeninos , Procedimientos Quirúrgicos Ginecológicos , Complicaciones Posoperatorias , Procedimientos Quirúrgicos Robotizados , Humanos , Femenino , Procedimientos Quirúrgicos Robotizados/efectos adversos , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiología , Neoplasias de los Genitales Femeninos/cirugía , Procedimientos Quirúrgicos Ginecológicos/métodos , Procedimientos Quirúrgicos Ginecológicos/efectos adversos , Complicaciones Intraoperatorias/epidemiología , Complicaciones Intraoperatorias/etiología , Adulto , Estudios de Cohortes , Anciano , Estudios Prospectivos , Reoperación/estadística & datos numéricos

RESUMEN

OBJECTIVES: The incidence of cervical cancer among patients with postcoital bleeding (PCB) was the primary objective of this study. Furthermore, the proportion of cervical intraepithelial neoplasia requiring treatment and the correlation between PCB and the presence of high-risk human papillomavirus (HPV) was determined. Lastly, the study aimed to identify risk factors among the referred women. METHODS: A retrospective cohort study was conducted at a university hospital in Denmark between January 1, 2017 and December 31, 2019. Women referred with PCB were identified with the ICD diagnosis codes "DN930 Postcoital and contact bleeding" and "DN930B Contact bleeding." Demographic and paraclinical data were extracted from the journals and the supportive systems: Patoweb and the Danish Microbiology Database. RESULTS: A total of 789 women were included in this study, with only 0.25% ( n = 2) diagnosed with cervical cancer and 2.5% ( n = 20) diagnosed with cervical intraepithelial neoplasia II-III and adenocarcinoma in situ. Human papillomavirus testing was only conducted in a minority of cases, and a low incidence of high-risk human papilloma virus was detected in the 22 cases, n = 5. CONCLUSIONS: A very low incidence of cervical cancer and high-grade cervical intraepithelial neoplasia reported among women referred with PCB. Prognostic factors as body mass index, smoking, and HPV vaccination status may predict the risk of cervical cancer. Selection criteria like primary testing for hrHPV and cytology as cotests before referral to colposcopy may reduce the number of unnecessary colposcopies.

Asunto(s)

Infecciones por Papillomavirus , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Humanos , Femenino , Estudios Retrospectivos , Neoplasias del Cuello Uterino/epidemiología , Incidencia , Adulto , Displasia del Cuello del Útero/epidemiología , Persona de Mediana Edad , Dinamarca/epidemiología , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/epidemiología , Adulto Joven , Factores de Riesgo , Anciano , Coito , Papillomaviridae/aislamiento & purificación , Hemorragia Uterina/epidemiología

RESUMEN

Importance: Active surveillance for cervical intraepithelial neoplasia grade 2 (CIN2) is being implemented in many high-income countries due to the association of excisional treatment with preterm birth. However, it is unknown whether active surveillance results in lower risk of preterm birth given that cervical dysplasia itself is associated with higher risk of preterm birth. Objective: To compare the preterm birth risk between women with CIN2 undergoing active surveillance or immediate loop electrosurgical excision procedure (LEEP). Design, Setting, and Participants: This historical population-based cohort study included women with a first-time diagnosis of CIN2 and a subsequent singleton birth from 1998 to 2018 in Denmark. Women with prior CIN grade 3 or greater or LEEP were excluded. Data were collected from 4 Danish health care registries. Analyses were conducted from October 2022 to June 2023. Exposure: Women were categorized into active surveillance (cervical biopsy and/or cytology) or immediate LEEP based on their first cervical sample after CIN2 diagnosis. The active surveillance group was further subdivided based on whether a delayed LEEP was performed within 28 months from CIN2 diagnosis. Main Outcomes and Measures: Risk of preterm birth (<37 + 0 weeks) was assessed and relative risks (RRs) were calculated using modified Poisson regression. Analyses used inverse probability treatment weighting of the propensity scores to adjust for age, parity, calendar year, index cytology, and smoking. Results: A total of 10 537 women with CIN2 and a singleton birth were identified; 4430 (42%) underwent active surveillance and 6107 (58%) were treated with immediate LEEP. For both groups, most were aged 23 to 29 years at CIN2 diagnosis (3125 [70%] and 3907 [64%], respectively). Overall, 869 births (8.2%) were preterm. The risk of preterm birth was comparable between active surveillance and immediate LEEP (RR, 1.03; 95% CI, 0.90-1.18). However, for women undergoing delayed LEEP after active surveillance (1539 of the active surveillance group [35%]), the risk of preterm birth was higher than for women treated with immediate LEEP (RR, 1.29; 95% CI, 1.08-1.55). Conclusions and relevance: In this cohort study of women with CIN2, the risk of preterm birth was comparable between active surveillance and immediate LEEP. However, delayed LEEP was associated with 30% higher risk of preterm birth than immediate LEEP. Thus, risk stratification at CIN2 diagnosis is important to identify women with increased risk of delayed LEEP.

Asunto(s)

Nacimiento Prematuro , Displasia del Cuello del Útero , Recién Nacido , Embarazo , Femenino , Humanos , Estudios de Cohortes , Nacimiento Prematuro/epidemiología , Espera Vigilante , Puntaje de Propensión

RESUMEN

BACKGROUND: In recent years, active surveillance has been introduced as an alternative to excisional treatment in younger women with cervical intraepithelial neoplasia grade 2 because regression rates are high and excisional treatment is associated with increased risk of preterm birth. However, early identification of women at increased risk of persistence/progression is important to ensure timely treatment. Evidence is limited on biomarkers that may be used to identify women at increased risk of persistence/progression. OBJECTIVE: This study aimed to describe human papillomavirus HPV type-specific persistence/progression in women undergoing active surveillance for cervical intraepithelial neoplasia grade 2. STUDY DESIGN: We conducted a historical cohort study of women aged 23 to 40 years diagnosed with cervical intraepithelial neoplasia grade 2 at Aarhus University Hospital from 2000 to 2010. Women were identified through the Danish Pathology Data Bank (DPDB) and were considered as undergoing active surveillance if they had a first record of a cervical biopsy within 2 years after index diagnosis and no loop electrosurgical excision procedure before this. Human papillomavirus genotyping was performed on archived tissue samples using the HPV SPF10-DEIA-LiPA25 system (DNA ELISA [enzyme-linked immunosorbent assay] HPV SPF10 kit and RHA HPV SPF10-LiPA25 kit). Persistence/progression was defined as having a record of cervical intraepithelial neoplasia grade ≥2 in the DPDB determined on the last and worst diagnosis on a biopsy or loop electrosurgical excision procedure specimen during follow-up. We estimated the relative risk (95% confidence interval) of persistence/progression using a modified Poisson model. RESULTS: A total of 455 women were included. Two-thirds were aged ≤30 years (73.8%) at index diagnosis, and nearly half had a high-grade index cytology (48.8%). Overall, 52.2% of all women had cervical intraepithelial neoplasia grade ≥2 during follow-up; 70.5% were human papillomavirus-16-positive and 29.5% were positive for other human papillomavirus types. Human papillomavirus-16 was associated with a significantly higher risk of persistence/progression (relative risk, 1.64; 95% confidence interval, 1.37-1.95) compared with non-human papillomavirus-16. The risk of persistence/progression was highest in human papillomavirus-16-positive women with a high-grade index cytology compared with human papillomavirus-16-positive women with a low-grade cytology (relative risk, 1.29; 95% confidence interval, 1.03-1.61), whereas no differences were observed across age groups. CONCLUSION: The highest risk of persistence/progression was observed among human papillomavirus-16-positive women, particularly those with associated high-grade cytology. These findings suggest that early excisional treatment should be considered in this group of women.

Asunto(s)

Progresión de la Enfermedad , Genotipo , Infecciones por Papillomavirus , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Humanos , Femenino , Displasia del Cuello del Útero/virología , Displasia del Cuello del Útero/patología , Displasia del Cuello del Útero/cirugía , Adulto , Neoplasias del Cuello Uterino/virología , Neoplasias del Cuello Uterino/patología , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/virología , Adulto Joven , Estudios de Cohortes , Clasificación del Tumor , Papillomaviridae/genética , Papillomaviridae/aislamiento & purificación , Espera Vigilante , Papillomavirus Humano 16/genética , Papillomavirus Humano 16/aislamiento & purificación , Dinamarca/epidemiología , Virus del Papiloma Humano

RESUMEN

High-risk human papillomavirus (hrHPV) is the cause of virtually all cervical cancers, most vaginal and anal cancers, and some vulvar cancer cases. With HPV testing becoming the primary screening method for cervical cancer, understanding the link between cervical hrHPV infection and the risk of other anogenital cancers is crucial. We assessed the risk of vulvar, vaginal and anal cancer and precancer (VIN2+, VaIN2+ and AIN2+) in a prospective cohort study including 455,349 women who underwent cervical hrHPV testing in Denmark from 2005 to 2020. We employed Cox proportional hazard models, adjusting for age, calendar year and HPV vaccination status, and estimated hazard ratios (HRs) and 95% confidence intervals (CI). We used the Aalen Johansen estimator to calculate the absolute risks of VIN2+, VaIN2+ and AIN2+. In total, 15% of the women were hrHPV positive at baseline. A positive cervical hrHPV test was associated with increased incidence of vulvar, vaginal and anal squamous cell carcinoma (SCC). Five-year risk estimates of VIN2+, VaIN2+ and AIN2+ among hrHPV-positive women (0.45%, 0.14% and 0.12%) were higher than among hrHPV-negative women (0.14%, 0.01% and 0.05%). Particularly high risk was observed among the hrHPV-positive women of the oldest age, with a history of anogenital precancer and those not HPV vaccinated. In conclusion, our study confirms the association between cervical hrHPV infection and non-cervical anogenital precancers and cancers. Currently, no established risk threshold or guidelines for follow-up. As HPV testing becomes the primary method for cervical cancer screening, future data will help define high-risk groups and acceptable risk thresholds.

Asunto(s)

Neoplasias del Ano , Infecciones por Papillomavirus , Lesiones Precancerosas , Neoplasias Vaginales , Neoplasias de la Vulva , Adulto , Anciano , Femenino , Humanos , Persona de Mediana Edad , Neoplasias del Ano/virología , Neoplasias del Ano/epidemiología , Carcinoma de Células Escamosas/epidemiología , Carcinoma de Células Escamosas/virología , Dinamarca/epidemiología , Detección Precoz del Cáncer , Incidencia , Papillomaviridae/aislamiento & purificación , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/epidemiología , Lesiones Precancerosas/epidemiología , Lesiones Precancerosas/virología , Estudios Prospectivos , Factores de Riesgo , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/virología , Neoplasias Vaginales/epidemiología , Neoplasias Vaginales/virología , Neoplasias de la Vulva/virología , Neoplasias de la Vulva/epidemiología

RESUMEN

OBJECTIVE: To describe the long term risk of cervical cancer in women with untreated (that is, undergoing active surveillance) or immediately treated cervical intraepithelial neoplasia grade 2 (CIN2). DESIGN: Nationwide population based historical cohort study. SETTING: Danish healthcare registries. PARTICIPANTS: Women with CIN2 diagnosed in 1998-2020 and aged 18-40 years at diagnosis, who had either active surveillance or immediate treatment with large loop excision of the transformation zone (LLETZ). Women with a previous record of CIN2 or worse or LLETZ were excluded. MAIN OUTCOME MEASURE: A Weibull survival model for interval censored time-to-event data was used to estimate the cumulative risk of cervical cancer. Inverse probability treatment weighting was used to adjust estimates for age, index cytology, calendar year, and region of residence. RESULTS: The cohort included 27 524 women with CIN2, of whom 12 483 (45%) had active surveillance and 15 041 (55%) had immediate LLETZ. During follow-up, 104 cases of cervical cancer were identified-56 (54%) in the active surveillance group and 48 (46%) in the LLETZ group. The cumulative risk of cervical cancer was comparable across the two groups during the active surveillance period of two years. Thereafter, the risk increased in the active surveillance group, reaching 2.65% (95% confidence interval 2.07% to 3.23%) after 20 years, whereas it remained stable in the LLETZ group at 0.76% (0.58% to 0.95%). CONCLUSIONS: Undergoing active surveillance for CIN2, thereby leaving the lesion untreated, was associated with increased long term risk of cervical cancer compared with immediate LLETZ. These findings show the importance of continued follow-up of women having active surveillance.

Asunto(s)

Infecciones por Papillomavirus , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Embarazo , Humanos , Femenino , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/cirugía , Neoplasias del Cuello Uterino/diagnóstico , Estudios de Cohortes , Colposcopía , Displasia del Cuello del Útero/patología , Infecciones por Papillomavirus/diagnóstico

RESUMEN

BACKGROUND: Concurrent chronic diseases and treatment hereof in patients with cancer may increase mortality. In this population-based study we examined the individual and combined impact of multimorbidity and polypharmacy on mortality, across 20 cancers and with 13-years follow-up in Denmark. MATERIALS AND METHODS: This nationwide study included all Danish residents with a first primary cancer diagnosed between 1 January 2005 and 31 December 2015, and followed until the end of 2017. We defined multimorbidity as having one or more of 20 chronic conditions in addition to cancer, registered in the five years preceding diagnosis, and polypharmacy as five or more redeemed medications 2-12 months prior to cancer diagnosis. Cox regression analyses were used to estimate the effects of multimorbidity and polypharmacy, as well as the combined effect on mortality. RESULTS: A total of 261,745 cancer patients were included. We found that patients diagnosed with breast, prostate, colon, rectal, oropharynx, bladder, uterine and cervical cancer, malignant melanoma, Non-Hodgkin lymphoma, and leukemia had higher mortality when the cancer diagnosis was accompanied by multimorbidity and polypharmacy, while in patients with cancer of the lung, esophagus, stomach, liver, pancreas, kidney, ovarian and brain & central nervous system, these factors had less impact on mortality. CONCLUSION: We found that multimorbidity and polypharmacy was associated with higher mortality in patients diagnosed with cancer types that typically have a favorable prognosis compared with patients without multimorbidity and polypharmacy. Multimorbidity and polypharmacy had less impact on mortality in cancers that typically have a poor prognosis.

Asunto(s)

Melanoma , Multimorbilidad , Masculino , Humanos , Estudios de Cohortes , Polifarmacia , Enfermedad Crónica , Sistema de Registros , Dinamarca/epidemiología

RESUMEN

BACKGROUND: Cervical intraepithelial neoplasia grade 2 has historically been the threshold for surgical excision, but because of high regression rates, many countries are transitioning to active surveillance. However, estimates for regression rates are based on small studies with heterogeneous definitions of regression and progression. OBJECTIVE: This study aimed to describe regression and progression rates of cervical intraepithelial neoplasia grade 2 using nationwide healthcare registry data. STUDY DESIGN: This was a nationwide population-based cohort study on women aged 18 to 40 years who had undergone active surveillance for cervical intraepithelial neoplasia grade 2 in Denmark from 1998 to 2020. This study excluded women with a previous record of cervical intraepithelial neoplasia grade 2 or worse or surgical excision. Cumulative incidence functions were used to estimate the rates of regression and progression at 6, 12, 18, and 24 months after diagnosis. In addition, a modified Poisson regression was used to estimate the crude and adjusted relative risks of progression within 24 months stratified by index cytology and age. RESULTS: During the study period, 11,056 women underwent active surveillance, 6767 of whom regressed and 3580 of whom progressed within 24 months. This corresponded to regression rates of 62.9% (95% confidence interval, 61.9-63.8) and progression rates of 33.3% (95% confidence interval, 32.4-34.2) at 24 months of follow-up. Most women regressed (90%) or progressed (90%) within the first 12 months. Women with high-grade index cytology had a higher risk of progression than women with normal index cytology (adjusted relative, 1.58; 95% confidence interval, 1.43-1.76), whereas there was no difference in the risk of progression between women aged 30 and 40 years and women aged 23 to 29 years (adjusted relative risk, 0.98; 95% confidence interval, 0.88-1.10). CONCLUSION: The observed high regression rates of cervical intraepithelial neoplasia grade 2 supported the transition in clinical management from surgical excision to active surveillance, particularly among women with low-grade or normal index cytology.

Asunto(s)

Infecciones por Papillomavirus , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Embarazo , Femenino , Humanos , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/cirugía , Estudios de Cohortes , Estudios de Seguimiento , Colposcopía , Displasia del Cuello del Útero/epidemiología , Progresión de la Enfermedad , Infecciones por Papillomavirus/diagnóstico

RESUMEN

Immunocompromised women are at increased risk of having HPV detected and developing HPV-related diseases such as genital warts, anogenital dysplasia, and cancer. This review aims to summarize the current literature regarding the immunogenicity of the HPV vaccine in immunocompromised women and to discuss whether HPV vaccination may be able to reduce the risk of cervical dysplasia and cancer. HPV vaccination induces an immune response in these women; however, it is unknown whether vaccination is effective in reducing the risk of cervical dysplasia and cancer. Further research is needed.

Asunto(s)

Condiloma Acuminado , Infecciones por Papillomavirus , Vacunas contra Papillomavirus , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Humanos , Femenino , Infecciones por Papillomavirus/prevención & control , Neoplasias del Cuello Uterino/etiología , Neoplasias del Cuello Uterino/prevención & control , Displasia del Cuello del Útero/prevención & control , Vacunación

RESUMEN

INTRODUCTION: Many countries have adopted active surveillance in women with cervical intraepithelial neoplasia grade 2 (CIN2), leaving the lesion untreated. However, there is a lack of consensus on the eligibility criteria for active surveillance across countries, with some abstaining from active surveillance in women with human papilloma virus 16 (HPV16) or a high-grade cytology. Here, we aimed to describe the distribution of HPV genotypes, age, and cytology in women undergoing active surveillance for CIN2. MATERIAL AND METHODS: We conducted a single-center cross-sectional study on women aged 23-40 undergoing active surveillance for CIN2 during 2000-2010. Women were identified through the Danish Pathology Data Bank (DPDB) at Aarhus University Hospital, Denmark. We collected information on basic characteristics and results of histopathological examinations via DPDB. Women were deemed eligible for inclusion if they had a subsequent biopsy after index CIN2, and had no prior record of CIN2+, hysterectomy, or cone biopsy. Archived biopsies underwent HPV genotyping using the HPV SPF10 - DEIA-LiPA25 system, and the diagnosis was re-evaluated by three expert pathologists. We used the Chi squared-test (p-value) for comparison across groups. RESULTS: We identified 3623 women with CIN2 of whom 455 (12.6%) were included. Most women were 30 years or younger (73.8%), and half (48.8%) had a high-grade index cytology. The prevalence of any high-risk HPV was 87.0%, with HPV16 being the most prevalent genotype (35.6%). The prevalence of HPV16 was significantly higher in women aged 30 or younger (39.3%) compared to women older than 30 years (25.2%) (p = 0.006). Upon expert review, 261 (57.4%) had CIN2 confirmed, whereas 56 (12.3%) were upgraded to CIN3 and 121 (26.6%) were downgraded to CIN1/normal. While the HPV16 prevalence was similar between community and expert confirmed CIN2, the prevalence of HPV16 was significantly higher in women with expert CIN3 compared to women with expert CIN1/normal (64.3% vs. 19.0%, p = 0.001). CONCLUSIONS: The high prevalence of HPV16 and high-grade cytology imply that these women may be perceived as a high-risk population and non-eligible for active surveillance in countries outside Denmark. Future studies should investigate the importance of HPV, age, cytology, and expert review on risk of progression to help refine criteria for active surveillance.

Asunto(s)

Infecciones por Papillomavirus , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Femenino , Humanos , Papillomavirus Humano 16/genética , Neoplasias del Cuello Uterino/patología , Infecciones por Papillomavirus/epidemiología , Prevalencia , Estudios Transversales , Espera Vigilante , Displasia del Cuello del Útero/patología , Genotipo , Papillomaviridae/genética , Detección Precoz del Cáncer

RESUMEN

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.

Asunto(s)

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 , Papillomaviridae

RESUMEN

BACKGROUND: The emergence of the COVID-19 pandemic and the derived changes in maternity care have created stress and anxiety among pregnant women in different parts of the world. In times of stress and crisis, spirituality, including spiritual and religious practices, may increase. OBJECTIVE: To describe if the COVID-19 pandemic influenced pregnant women's considerations and practises of existential meaning-making and to investigate such considerations and practices during the early pandemic in a large nationwide sample. METHODS: We used survey data from a nationwide cross-sectional study sent to all registered pregnant women in Denmark during April and May 2020. We used questions from four core items on prayer and meditation practices. RESULTS: A total of 30,995 women were invited, of whom 16,380 participated (53%). Among respondents, we found that 44% considered themselves believers, 29% confirmed a specific form of prayer, and 18% confirmed a specific form of meditation. In addition, most respondents (88%) reported that the COVID-19 pandemic had not influenced their responses. CONCLUSION: In a nationwide Danish cohort of pregnant women, existential meaning-making considerations and practices were not changed due to the COVID-19 pandemic. Nearly one in two study participants described themselves as believers, and many practised prayer and/or meditation.

Asunto(s)

COVID-19 , Servicios de Salud Materna , Meditación , Femenino , Humanos , Embarazo , Mujeres Embarazadas , COVID-19/epidemiología , Pandemias , Estudios Transversales , Encuestas y Cuestionarios , Dinamarca/epidemiología

RESUMEN

INTRODUCTION: We identified risk factors and outcomes associated with SARS-CoV-2 infection in pregnancy in a universally tested population according to disease severity and validated information on SARS-CoV-2 during pregnancy in national health registers in Denmark. MATERIAL AND METHODS: Cohort study using data from national registers and medical records including all pregnancies between March 1, 2020 and February 28, 2021. We compared women with a validated positive SARS-CoV-2 test during pregnancy with non-infected pregnant women. Risk factors and pregnancy outcomes were assessed by Poisson and Cox regression models and stratified according to disease severity defined by hospital admission status and admission reason (COVID-19 symptoms or other). Using medical record data on actual period of pregnancy, we calculated predictive values of the SARS-CoV-2 diagnosis in pregnancy in the registers. RESULTS: SARS-CoV-2 infection was detected in 1819 (1.6%) of 111 185 pregnancies. Asthma was associated with infection (relative risk [RR] 1.63, 95% confidence interval [CI] 1.28-2.07). Risk factors for severe COVID-19 disease requiring hospital admission were high body mass index (median ratio 1.06, 95% CI 1.04-1.09), asthma (RR 7.47, 95% CI 3.51-15.90) and gestational age at the time of infection (gestational age 28-36 vs < 22: RR 3.53, 95% CI 1.75-7.10). SARS-CoV-2-infected women more frequently had hypertensive disorders in pregnancy (adjusted hazard ratio [aHR] 1.31, 95% CI 1.04-1.64), early pregnancy loss (aHR 1.37, 95% CI 1.00-1.88), preterm delivery before gestational age 28 (aHR 2.31, 95% CI 1.01-5.26), iatrogenically preterm delivery before gestational age 37 (aHR 1.49, 95% CI 1.01-2.19) and small-for-gestational age children (aHR 1.28, 95% CI 1.05-1.54). The associations were stronger among women admitted to hospital for any reason. The validity of the SARS-CoV-2 diagnosis in relation to pregnancy in the registers compared with medical records showed a negative predictive value of 99.9 (95% CI 99.9-100.0) and a positive predictive value of 82.1 (95% CI 80.4-83.7). CONCLUSIONS: Women infected with SARS-CoV-2 during pregnancy were at increased risk of hypertensive disorders in pregnancy, early pregnancy loss, preterm delivery and having children small for gestational age. The validity of Danish national registers was acceptable for identification of SARS-CoV-2 infection during pregnancy.

Asunto(s)

Aborto Espontáneo , Asma , COVID-19 , Hipertensión Inducida en el Embarazo , Complicaciones Infecciosas del Embarazo , Nacimiento Prematuro , Recién Nacido , Niño , Femenino , Embarazo , Humanos , Adulto , SARS-CoV-2 , Resultado del Embarazo/epidemiología , COVID-19/diagnóstico , COVID-19/epidemiología , Estudios de Cohortes , Nacimiento Prematuro/epidemiología , Prueba de COVID-19 , Complicaciones Infecciosas del Embarazo/diagnóstico , Complicaciones Infecciosas del Embarazo/epidemiología , Factores de Riesgo , Gravedad del Paciente

RESUMEN

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.

Asunto(s)

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 Vaginal

RESUMEN

OBJECTIVE: To measure anxiety levels in women aged ≥45 years undergoing diagnostic large loop excision of the transformation zone (LLETZ) at the first colposcopy visit. DESIGN: Longitudinal study. SETTING: Three colposcopy clinics in the Central Denmark Region. POPULATION: Women aged ≥45 years undergoing diagnostic LLETZ. METHODS: Women completed the State-Trait Anxiety Inventory (STAI) and Short Form 12 (mental and physical health) questionnaires before, immediately after, and at 1 and 6 months after LLETZ. MAIN OUTCOME MEASURES: STAI state anxiety median scores were calculated and stratified by health status, by letter with information about screening result and by LLETZ results. RESULTS: Of 109 eligible women, 11 were excluded, leaving 98 women for the final analyses. Response rates ranged from 84.7% to 100%. Overall, state anxiety levels were low; however, a decrease was observed from before to immediately after the LLETZ (33.4 vs 29.3, p < 0.001). The anxiety levels remained stable up to 6 months after LLETZ. Women with poor mental health were more likely to have higher anxiety levels compared with women with good mental health (before LLETZ, RR 3.77, 95% CI 2.12-6.70; 1 month after LLETZ, RR 3.37, 95% CI 1.59-7.15; 6 months after LLETZ, RR 1.93, 95%CI 1.06-3.51). CONCLUSIONS: Overall, colposcopy and diagnostic LLETZ in women aged ≥45 years were not associated with high levels of anxiety. Anxiety levels were highest before colposcopy, and the women seemed to experience immediate relief afterwards. Women with poor mental health had the highest anxiety levels throughout the study, which might call for special attention.

Asunto(s)

Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Femenino , Humanos , Embarazo , Neoplasias del Cuello Uterino/diagnóstico , Estudios Longitudinales , Colposcopía/métodos , Ansiedad/etiología , Displasia del Cuello del Útero/diagnóstico

RESUMEN

BACKGROUND: Patients with BRAF V600E mutated metastatic colorectal cancer (mCRC) have a poor prognosis. The introduction of BRAF targeted therapy with encorafenib and weekly administered cetuximab have shown improved survival with a median progression free survival (PFS) of 4.3 months. However, a regimen with cetuximab given every second week may have comparable efficacy and is more convenient for patients. While BRAF targeted therapy is a new standard therapy in pre-treated patients with BRAF V600E mutated mCRC, resistance invariably occurs and is an emerging challenge. The aim of this study is to investigate the efficacy and tolerability of cetuximab given every second week in combination with daily encorafenib and to explore the correlation between markers of resistance and outcome. METHODS: The study is an open label, single arm, phase II study, investigating the efficacy and tolerability of cetuximab given every second week in combination with encorafenib in patients with BRAF V600E mutated mCRC. Furthermore, we will be investigating mechanisms of response and resistance against BRAF targeted therapy though comprehensive genomic profiling on tumor tissue and blood for circulating tumor DNA analysis. A total of 53 patients (19 + 34 in two steps) will be included according to Simon's optimal two stage design. The primary end point of the study is 2 months PFS rate. DISCUSSION: By combining BRAF inhibitor with cetuximab given every second week we can halve the number of visits in the hospital compared to the currently approved regimen with weekly cetuximab. This seems particularly relevant in a group of patients with a median overall survival of 9.3 months. Resistance after initial response to targeted therapy can be either adaptive (e.g., epigenetic, or transcriptomic alterations) or acquired (selective genetic alterations - e.g., activating de novo mutations) resistance. It is of great importance to untangle these complex mechanisms of resistance in patients with BRAF V600E mutated mCRC to improve treatment strategies in the future potentially even further. TRIAL REGISTRATION: EU Clinical Trial Register, Eudract no. 2020-003283-10 . Registered on 11 November 2020.

Asunto(s)

Neoplasias del Colon , Neoplasias Colorrectales , Neoplasias del Recto , Humanos , Cetuximab/efectos adversos , Proteínas Proto-Oncogénicas B-raf/genética , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Mutación , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Recto/tratamiento farmacológico

RESUMEN

BACKGROUND: Shared decision-making (SDM) is a process aimed at facilitating patient-centered care by ensuring that the patient and provider are actively involved in treatment decisions. In mental health care, SDM has been advocated as a means for the patient to gain or regain control and responsibility over their life and recovery process. To support the process of patient-centered care and SDM, digital tools may have advantages in terms of accessibility, structure, and reminders. OBJECTIVE: In this randomized controlled trial, we aimed to investigate the effect of a digital tool to support patient activation and SDM. METHODS: The trial was designed as a randomized, assessor-blinded, 2-armed, parallel-group multicenter trial investigating the use of a digital SDM intervention for 6 months compared with treatment as usual. Participants with a diagnosis of schizophrenia, schizotypal or delusional disorder were recruited from 9 outpatient treatment sites in the Capital Region of Denmark. The primary outcome was the self-reported level of activation at the postintervention time point. The secondary outcomes included self-efficacy, hope, working alliance, satisfaction, preparedness for treatment consultation, symptom severity, and level of functioning. Explorative outcomes on the effect of the intervention at the midintervention time point along with objective data on the use of the digital tool were collected. RESULTS: In total, 194 participants were included. The intention-to-treat analysis revealed a statistically significant effect favoring the intervention group on patient activation (mean difference 4.39, 95% CI 0.99-7.79; Cohen d=0.33; P=.01), confidence in communicating with one's provider (mean difference 1.85, 95% CI 0.01-3.69; Cohen d=0.24; P=.05), and feeling prepared for decision-making (mean difference 5.12, 95% CI 0.16-10.08; Cohen d=0.27; P=.04). We found no effect of the digital SDM tool on treatment satisfaction, hope, self-efficacy, working alliance, severity of symptoms, level of functioning, use of antipsychotic medicine, and number or length of psychiatric hospital admissions. CONCLUSIONS: This trial showed a significant effect of a digital SDM tool on the subjective level of patient activation, confidence in communicating with one's provider, and feeling prepared for decision-making at the postintervention time point. The effect size was smaller than the 0.42 effect size that we had anticipated and sampled for. The trial contributes to the evidence on how digital tools may support patient-centered care and SDM in mental health care. TRIAL REGISTRATION: ClinicalTrials.gov NCT03554655; https://clinicaltrials.gov/ct2/show/NCT03554655. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-doi: 10.1186/s12888-019-2143-2.

Asunto(s)

Antipsicóticos , Aplicaciones Móviles , Esquizofrenia , Humanos , Participación del Paciente , Esquizofrenia/diagnóstico , Esquizofrenia/terapia , Pacientes Ambulatorios , Toma de Decisiones