Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Rare Diseases

Uterine Cervical Neoplasms

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Neuroendocrine Tumor

Neuroepithelioma

Binhua Dong

Pengming Sun

Dongjie Chen

Fang Xie

Yi Chen

Luhong Li

Feifeng Shi, M.D

Hongning Cai, M.D

Yu Zhang

Ling Li

Pengming Sun, PhD

The clinical diagnosis and treatment data of 300 cases of cervical neuroendocrine tumors were collected, including age, preoperative biopsy pathology results, postoperative histopathological results, TCT results, and colposcopy biopsy pathology results. At the same time, paraffin tissue specimens (remaining specimens after pathological diagnosis) from 100 cases of cervical neuroendocrine tumors from multiple centers across the country were collected to establish a cervical neuroendocrine tumor data follow-up database. Protein concentration and omics analysis were performed on the data results, to evaluate the molecular characteristics and prognosis of cervical neuroendocrine tumor proteins, and to preliminarily explore its clinical application value.

1. The clinical diagnosis and treatment data of 300 cases of cervical neuroendocrine tumors were used for prognostic analysis.

(1) The diagnosis and treatment information of cervical neuroendocrine carcinoma in multiple hospitals was collected, including clinical and medical data such as age, preoperative HPV genotyping, preoperative biopsy pathological results, postoperative histopathological results, FIGO staging, prognosis and survival information, and follow-up of patients.

2. Protein and other omics analysis was performed on paraffin tissues of 100 cases of cervical neuroendocrine tumors Paraffin samples collected from 100 cases of cervical neuroendocrine tumors were identified, processed and segmtioned, and protein concentration and proteome were determined to establish the molecular characteristics and prognostic targets of cervical neuroendocrine tumors.

Paraffin samples collected from 100 cases of cervical neuroendocrine tumors were identified, processed and segmtioned, and protein concentration and proteome were determined to establish the molecular characteristics and prognostic targets of cervical neuroendocrine tumors.

Protein Molecular Characteristics and Prognosis of Cervical Neuroendocrine Tumors

3-year mortality rate for cervical neuroendocrine carcinoma

3-year disease-free survival for cervical neuroendocrine carcinoma

Fujian Maternity and Child Health Hospital

Uterine Cervical Diseases

Uterine Cervical Dysplasia

Uterine Neoplasms

Genital Neoplasms, Female

Urogenital Neoplasms

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Precancerous Conditions

Cervical Intraepithelial Neoplasia

Anti-Infective Agents

All Drugs and Chemicals

Antineoplastic Agents

Micronutrients

Coagulants

Vitamins

Acetic Acid

Retinol acetate

Iodine

Lugol's solution

Cadexomer iodine

Swede score colposcopy: includes application with acetic acid, supplemented with a systematic scoring system (the Swede score) including Lugols iodine, and collection of cervical biopsies.

Conventional colposcopy: includes application with acetic acid and collection of cervical biopsies.

New colposcopy method: with application of acetic acid, supplemented with a systematic scoringsystem (Swede score) including Lugols iodine, and collection of cervical biopsies.

Swede score colposcopy

Ane-Kersti Knudsen, MD,Ph.d.stud

Rikke Guldberg

Anne Hammer

Helene Nortvig

Christina Blach

Lone Kjeld Petersen

Eva Hauge

Attila Botházi

Anne Hammer, MD, as.prof

Ulrik Schiøler Kesmodel, MD, prof

Berit Bargum Booth, MD, Ph.d.

Line Winther Gustafson, MD, Ph.d.

Cervical cancer screening is important as it enables identification of women at increased risk of the disease, but high-quality diagnostics of screen-positive women and effective treatment of those with precancer are critical in preventing progression to cancer. With the current transition from cytology-based to primary human papillomavirus (HPV)-screening and a growing proportion of HPV-vaccinated women, diagnostics of screen-positive women will become more challenging in the decades to come. Thus, there is a need to explore how to improve diagnostics while ensuring a low number of unnecessary procedures such as colposcopy and the collection of multiple cervical biopsies.

The overall purpose is:

* To investigate the diagnostic accuracy of cervical precancer when using a colposcopic scoring system in the diagnostic work-up of screen-positive women.
* To investigate the performance of a colposcopic scoring system to identify women without cervical precancer in whom collection of biopsies can be safely omitted.

Introduction Cervical cancer is the fourth most common cancer in women worldwide. Every year, 375 women are diagnosed with cervical cancer in Denmark, and approximately 90 women die from the disease. Cervical cancer is caused by the sexually transmitted virus, human papillomavirus (HPV). When infected about 85-90 % clear the virus within a year or two. The remaining women develop a persistent HPV infection, which is associated with an increased risk of cervical intraepithelial neoplasia (CIN), which may progress to cancer if left untreated. Cervical cancer can be prevented through prophylactic HPV vaccination and screening. In Denmark, women aged 23 - 64 years are invited to the screening program. Women who do not participate in regular screening have an increased risk of cervical cancer, however up to 55% of cervical cancers are diagnosed in women who have attended screening. Hence, the performance of diagnostics is crucial.

Diagnostics Women with abnormal screening results may undergo repeat testing or be referred for colposcopy. Colposcopy allows the colposcopist to magnify and visualize the cervix with the transformation zone, where cervical cancer and cervical lesions typically arise. The aim is to make a colposcopic diagnosis and select the most severe area for biopsies, which undergo histopathological examination. Studies have shown considerable inter- and intra-observer variability even among experienced colposcopists, and a variable sensitivity of colposcopy as low as 55-57%. These findings suggest a need to improve the detection rate of CIN2+. A validated colposcopic scoring system, the Swede score, has been designed to improve the detection of high-grade cervical lesions, specified as cervical intraepithelial neoplasia grade 2 or worse (CIN2+) by providing an systematic approach to the colposcopy examination. The Swede score includes five variables (degree of 1) acetowhitening, 2) margins and surface, 3) vessels, 4) lesion size, and 5) iodine staining by using Lugols iodine) with a score from 0 - 2. Conventional colposcopy only utilizes acetic acid. In the original study, the Swede score had a high sensitivity and specificity for detecting high-grade cervical lesions (CIN2+), with an area under the receiver operating characteristics (ROC) curve of 0.87. Even so, the Swede score is endorsed by the International Agency for Research on Cancer (IARC/WHO) and by the European Federation for Colposcopy (EFC), it has not yet been implemented in Denmark. As previous studies have mostly evaluated the use of the Swede score among expert colposcopists, it is important to assess whether the score may be a valuable tool among non-experts. In Denmark, colposcopy is mostly performed by non-experts gynecologists. As a result of the low performance of colposcopy, and because several studies have shown that the CIN2+ detection rate increases with the number of biopsies collected, the Danish national guidelines recommend that all women should have a minimum of 4 biopsies collected. Biopsies should be collected from abnormal areas of the cervix and, if no lesion is detected, random biopsies should be taken. Our neighboring Scandinavian countries, for example Sweden and Finland, do not recommend collection of random biopsies. If biopsies could be omitted without increasing the risk of missing disease and reducing the harms with pain, bleeding and discomfort, this would benefit the women.

Aim The project aims to explore whether the implementation of a systematic colposcopic scoring system, the Swede score, can improve diagnostic accuracy of cervical lesions with detection of CIN2+ in a Danish clinical setting. Furthermore, we want to evaluate whether the Swede score can be used to assess when random biopsies can be safely omitted.

Data Characteristics of the women will be collected from medical records (previous gynecological historic, parity, smoking status, HPV-vaccination status, hormone use or immunosuppressive treatment). From the Danish Pathology Databank, we will collect data on previous screening history, result of the referral screening test, result of current and subsequent cervical biopsies and/or cervical excision.

This study is focused on cervical cancer and precancer. Since only women have a cervix, only women will be included in this study.

iMproving thE DIagnostics And Treatment Of ceRvical Precancer

The number of women diagnosed with Cervical Intraepithelial Neoplasia grade 2 or worse (CIN2+) diagnosed in cervical biopsies

University of Aarhus

Infections

Symptoms and General Pathology

Vaccine-Preventable Diseases

Communicable Diseases

Patients who have been vaccinated against HPV virus.

Patients who have not been vaccinated against HPV virus.

Philippe MERVIEL, PU-PH

Each year in France, more than 6000 new cases of HPV inducted cancers are recorded. The vaccinal cover stays insufficient since less than 30% of the french population is vaccinated. Therefore french studies about vaccine efficacy and especially about the catch-up vaccine (done after 15years old) are needed.

HPVAC2 is a prospective, analytic and monocentric study designed to learn the impact of the catch-up HPV vaccination.

Women from 25 years old and born after 1984 may be included if they come to the Brest CHU to do their regular cervical smear. At this time, a survey will be given to know their vaccinal status.

The aim of the study is to prove the efficacy of the catch up vaccination by analyzing the cervical smears results and by comparing the vaccinated group with the not-vaccinated group.

Impact of Catch-up HPV Vaccination

Impact of Catch-up HPV Vaccination on the Development of Cervical Lesions

Study the effectiveness of anti-HPV vaccine (done between 15 and 19 years old).

Study the effectiveness of anti-HPV vaccine (done between 11 and 15 years old).

Study the effectiveness of anti-HPV vaccine (not regarding the period of realization)

Compare the effectiveness of anti-HPV vaccine done before and after 15 years old.

Study the impact of the known cervical cancer risk factors on the smear results.

University Hospital, Brest

Cone biopsi is offered to women age ≥ 45 years referred to Department of Obstetrics and Gynecology due to a positive cervical screening test and partly or invisible transformation zone.

Cone biopsy if transformation Zone (TZ) 2 or TZ 3

Cone biopsy

Line W Gustafson, MD

The study will investigate if implementation of "see and treat" in the outpatient clinic can optimize the diagnosis, clinical follow-up and treatment of older women with positive cervical screening test.

In Denmark, 370 women are diagnosed with cervical cancer every year and approximately 100 women die from the disease. Young women can be protected with the HPV vaccine, but it will take decades before the vaccine has an effect on older women. Women who are HPV positive have a risk of developing severe dysplasia of 25-55% within 10 years. Compared to younger women, older women are also more likely to be diagnosed with advanced-stage disease and their mortality is high. Due to retraction of the transformation zone into the cervical canal and atrophy of the mucosa the performance of colposcopy is low. Furthermore, the sensitivity of cytology decreases with age. This makes it very difficult to obtain sufficient biopsies and therefore postmenopausal women are often required to undergo colposcopy two to three times. Waiting for a final diagnosis and treatment not only has a large mental and practical impact on the women themselves, but it is also an economic burden for the health care system.

"See and treat" is a procedure that involves cervical cytology and HPV test, a colposcopy, cervical biopsies, and finally a loop electrosurgical excisional procedure by which the transformation zone is removed. This approach allows women to be diagnosed and treated in one visit.

In this project, the aim is to investigate if the implementation of "see and treat" in a gynecological outpatient clinic can optimize the diagnostics, clinical follow-up, and treatment of older women with abnormal cervical cytology or HPV-infection.

Participants Women aged ≥ 45 years with cervical dysplasia and/or a positive HPV test are referred from the general practitioner to the gynecological department.

Procedure At each inclusion site, the local project manager evaluates all the referred women for possible inclusion. Project information is sent either by e-mail or letter to eligible women. At the outpatient clinic, the eligible women will be informed about the project and asked to sign an informed consent form regarding their participation in the project.

If the eligible women agree to participate a physician in the outpatient clinic will obtain a cervical smear (i.e. cytology and Human Papillomavirus (HPV) test) and perform colposcopy and take four random biopsies. If the transformation zone (TZ) is partly visible or not visible a cone biopsy will be performed in local anesthesia (Citanest).

If the participant meet the exclusion criteria or declines to participate standard treatment will be offered (colposcopy and biopsies).

The included patients will be followed up with an HPV test after 6 months.

See and Treat in an Outpatient Setting in Women Above 45 Years With Cervical Dysplasia

The dataset generated and analyzed in this study are not available for the public due to Danish legislation.

The prevalence of CIN2+ lesions in women ≥45 years included in the study

Concordance between cytology, biopsies and cone biopsy in the ability to detect CIN2+ changes

Complication rate of bleeding, infection and/or stenosis

Women referred to colposcopy at our facilities who met inclusion criteria

Women who have a colposcopy exam performed at Randers Regional Hospital were examined by Dynamic Spectral Imaging colposcopy (DYSIS)

Dynamic Spectral Imaging (DYSIS)

Berit B Booth, MD

Berit B Booth

Christina B Kristensen, MD

Pinar Bor, MD, PhD

Lone K Petersen, MD, Med.Sc.D.

Jan Blaakaer, MD, Med.Sc.D.

Katja Dahl, MD, PhD

This study evaluates the Dynamic Spectral Imaging (DSI) Colposcope (DySIS) in it's ability to diagnose cervical dysplasia. Half of participants with be examined by the DySIS colposcope, there the other half will be examined by standard colposcopy.

Colposcopy has been shown to be a subjective exam, and is dependant on the colposcopists. Sensitivity for colposcopy has been shown to be as low as 50%.

To improve this, different adjunctive technologies have been introduced to add a more objective approach to the colposcopy exam. One of these devices is the DySIS colposcope, which measures the aceto-white reaction that may occur on the cervix uteri after the application of acetic-acid. The device provides the examiner with a colour-coded map indicating areas of interest. Studies have shown promising results indicating that using this device together with the colposcopists own interpretation of the cervix uteri can potentially lead to an increase in the performance of the colposcopy exam.

In Denmark all women referred for colposcopy have 4 biopsies taken, according to the Danish national guidelines.

In our study these 4 biopsies are as following:

1. The area the colposcopists views as the worst before the DSI-map is seen. Colposcopy-Directed Biopsy (CDB)
2. The area indicated as the worst by the DSI-map (DSI-directed biopsy)
3. additional biopsy
4. additional biopsy All biopsies are placed in separate containers and analysed separately by specialized pathologists.

Colposcopy and Dynamic Spectral Imaging (DSI)

Does Dynamic Spectral Imaging (DSI) Colposcopy Improve the Diagnostics of Cervical Dysplasia Compared to Standard Colposcopy

The proportion of women who are found with a histological CIN2+ diagnosis in the cervical punch biopsy from the area chosen by the colposcopist before the DSI-map became visible (will be referred to as the Colposcopy directed biopsy (CDB)).

The diagnosis of the biopsy will be recorded when the histological report is available.

Further treatment needs for the patient will be based on the national clinical guidelines on cervical dysplasia.

The proportion of women who are found with a histological CIN2+ diagnosis in cervical punch biopsy taken from the worst area indicated by the DSI-map (referred to as the DSI-directed biopsy) The diagnosis of the biopsy will be recorded when the histological report is available.

Further treatment needs for the patient will be based on the national clinical guidelines on cervical dysplasia.

The amount of women who are found with a histological CIN2+ diagnosis in cervical punch biopsies taken from 2 additional areas besides the CDB and the DSI-directed areas.

The diagnosis of the biopsy will be recorded when the histological report is available.

Further treatment needs for the patient will be based on the national clinical guidelines on cervical dysplasia.

Comparing the histological diagnosis of the cervical punch biopsies to the cone biopsy, in women who are referred for conization based on the histological outcome of the colposcopy procedure.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Protein Molecular Characteristics and Prognosis of Cervical Neuroendocrine Tumors	NCT06276309	Neuroendocrine ... China Women Cervical Cancer Cervical Lesion		-	Fujian Maternity and Child Health Hospital
iMproving thE DIagnostics And Treatment Of ceRvical Precancer	NCT05870787	Cervical Dyspla... Cervical Diseas... Cervical Lesion Cervical Cancer Cervical Neopla...	Swede score col...	23 Years - 99 Years	University of Aarhus
Impact of Catch-up HPV Vaccination	NCT05462249	HPV HPV Vaccination Vaccine Prevent... Cervical Lesion Cervical Cancer		25 Years - 38 Years	University Hospital, Brest
See and Treat in an Outpatient Setting in Women Above 45 Years With Cervical Dysplasia	NCT04298957	Cervical Dyspla... Cervical Lesion Cervix Disease	Cone biopsy	45 Years -	University of Aarhus
Colposcopy and Dynamic Spectral Imaging (DSI)	NCT04249856	Cervical Dyspla... Cervical Diseas... Cervical Lesion Cervix Cancer Cervical Cancer Cervical Neopla...	Dynamic Spectra...	18 Years -	University of Aarhus
Impact of Catch-up HPV Vaccination	NCT05462249	HPV HPV Vaccination Vaccine Prevent... Cervical Lesion Cervical Cancer		25 Years - 38 Years	University Hospital, Brest

Spots Global Cancer Trial Database for cervical lesion